Ignite Creation Date:
2025-12-24 @ 7:18 PM
Ignite Modification Date:
2026-01-04 @ 4:20 AM
Study NCT ID:
NCT04079803
Status:
COMPLETED
Last Update Posted:
2021-09-29
First Post:
2019-08-26
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
PTI-125 for Mild-to-moderate Alzheimer's Disease Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2021-05-05', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000544', 'term': 'Alzheimer Disease'}], 'ancestors': [{'id': 'D003704', 'term': 'Dementia'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D024801', 'term': 'Tauopathies'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000719508', 'term': 'Simufilam'}, {'id': 'D013607', 'term': 'Tablets'}], 'ancestors': [{'id': 'D004304', 'term': 'Dosage Forms'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'nfriedmann@cassavasciences.com', 'phone': '512-501-1900', 'title': 'Nadav Friedmann, PhD, MD, Chief Medical Officer', 'organization': 'Cassava Sciences, Inc.'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '28 days', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo Cohort', 'description': 'Subjects administered placebo tablets twice daily (BID) for 28 days.', 'otherNumAtRisk': 22, 'deathsNumAtRisk': 22, 'otherNumAffected': 12, 'seriousNumAtRisk': 22, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Subjects administered simufilam 100 mg tablets twice daily (BID) for 28 days.', 'otherNumAtRisk': 21, 'deathsNumAtRisk': 21, 'otherNumAffected': 9, 'seriousNumAtRisk': 21, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Subjects administered simufilam 50 mg tablets twice daily (BID) for 28 days.', 'otherNumAtRisk': 21, 'deathsNumAtRisk': 21, 'otherNumAffected': 4, 'seriousNumAtRisk': 21, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 21, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 21, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Medra'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 21, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 21, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Medra'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 21, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 21, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Medra'}, {'term': 'Any adverse event', 'stats': [{'groupId': 'EG000', 'numAtRisk': 22, 'numEvents': 20, 'numAffected': 12}, {'groupId': 'EG001', 'numAtRisk': 21, 'numEvents': 15, 'numAffected': 9}, {'groupId': 'EG002', 'numAtRisk': 21, 'numEvents': 9, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Medra'}], 'frequencyThreshold': '4'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline in CSF Abeta42', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo tablets BID for 28 days'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'simufilam 100 mg tablets BID for 28 days'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'simufilam 50 mg tablets BID for 28 days'}], 'classes': [{'categories': [{'measurements': [{'value': '4.8', 'spread': '30.9', 'groupId': 'OG000'}, {'value': '12.5', 'spread': '11.9', 'groupId': 'OG001'}, {'value': '16.2', 'spread': '21.1', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.087', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing two subjects with no detectable simufilam in plasma, P=0.0088 and CFB was 13.4. In percent change from baseline with these two subjects removed, P=0.004.'}, {'pValue': '0.01', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing one subject with no detectable simufilam in plasma, P=0.0006 and CFB was 16.9. In percent change from baseline with this subject removed, P=0.0004.'}], 'paramType': 'MEAN', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample. This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in CSF Total Tau.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo oral tablets administered twice daily (BID)'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125) 100 mg Tablets Cohort', 'description': 'Simufilam (PTI-125) 100 mg oral tablets administered twice daily (BID)'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125) 50 mg Tablets Cohort', 'description': 'SImufilam (PTI-125) 50 mg oral tablets administered twice daily (BID)'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.2', 'spread': '14.8', 'groupId': 'OG000'}, {'value': '-18.7', 'spread': '10.4', 'groupId': 'OG001'}, {'value': '-14.6', 'spread': '9.6', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing two subjects with no detectable simufilam in plasma, P\\<0.0001 and CFB was -19.8.'}, {'pValue': '0.0012', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing one subject with no detectable simufilam in plasma, P=0.001 and CFB was -14.9.'}], 'paramType': 'MEAN', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample. This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in CSF P-tau181', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo tablets BID for 28 days'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'simufilam 100 mg tablets BID for 28 days'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'simufilam 50 mg tablets BID for 28 days'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.63', 'spread': '1.8', 'groupId': 'OG000'}, {'value': '-3.1', 'spread': '1.7', 'groupId': 'OG001'}, {'value': '-2.4', 'spread': '1.6', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.005', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing two subjects with no detectable simufilam in plasma, P=0.003 and CFB was -3.2.'}, {'pValue': '0.002', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing one subject with no detectable simufilam in plasma, P=0.003 and CFB was -2.5.'}], 'paramType': 'MEAN', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample. This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in CSF Neurogranin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo tablets BID for 28 days'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'simufilam 100 mg tablets BID for 28 days'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'simufilam 50 mg tablets BID for 28 days'}], 'classes': [{'categories': [{'measurements': [{'value': '-50.5', 'spread': '434', 'groupId': 'OG000'}, {'value': '-648', 'spread': '491', 'groupId': 'OG001'}, {'value': '-527', 'spread': '361', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0002', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing two subjects with no detectable simufilam in plasma, P=0.0002 and CFB was -681.'}, {'pValue': '0.0005', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing one subject with no detectable simufilam in plasma, P=0.0005 and CFB was -527.'}], 'paramType': 'MEAN', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample. This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in CSF Neurofilament Light Chain', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo tablets BID for 28 days'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'simufilam 100 mg tablets BID for 28 days'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'simufilam 50 mg tablets BID for 28 days'}], 'classes': [{'categories': [{'measurements': [{'value': '-10.0', 'spread': '45', 'groupId': 'OG000'}, {'value': '-76.3', 'spread': '50.6', 'groupId': 'OG001'}, {'value': '-49.7', 'spread': '35.5', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0003', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing two subjects with no detectable simufilam in plasma, P=0.0002 and CFB was -78.5.'}, {'pValue': '0.0058', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing one subject with no detectable simufilam in plasma, P=0.0008 and CFB was -51.0.'}], 'paramType': 'MEAN', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample. This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in CSF YKL-40', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo tablets BID for 28 days'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'simufilam 100 mg tablets BID for 28 days'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'simufilam 50 mg tablets BID for 28 days'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.96', 'spread': '24.2', 'groupId': 'OG000'}, {'value': '-22.3', 'spread': '11.7', 'groupId': 'OG001'}, {'value': '-20.4', 'spread': '17.4', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing two subjects with no detectable simufilam in plasma, P=0.0001 and CFB was -23.7.'}, {'pValue': '0.0001', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'P value adjusted for multiplicity of 6 co-primary endpoints (p\\<0.008 required for significance).', 'groupDescription': 'This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.', 'otherAnalysisDescription': 'In a secondary analysis removing one subject with no detectable simufilam in plasma, P=0.0002 and CFB was -20.9.'}], 'paramType': 'MEAN', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) in cerebrospinal fluid YKL-40', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample. This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).'}, {'type': 'SECONDARY', 'title': 'Paired Associates Learning Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo oral tablets administered twice daily (BID) for 28 days.'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Simufilam 100 mg oral tablets administered twice daily (BID) for 28 days.'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Simufilam 50 mg oral tablets administered twice daily (BID) for 28 days.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.5', 'spread': '8.5', 'groupId': 'OG000'}, {'value': '-4.5', 'spread': '17.7', 'groupId': 'OG001'}, {'value': '-5.7', 'spread': '13.6', 'groupId': 'OG002'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Effect size', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.23', 'estimateComment': "Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was identical when calculated by Cohen's d.", 'groupDescription': 'This study was not powered for statistical significance on cognitive measures.', 'nonInferiorityType': 'OTHER'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'Effect size', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.37', 'estimateComment': "Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was identical when calculated by Cohen's d.", 'groupDescription': 'This study was not powered for statistical significance on cognitive measures.', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 28', 'description': 'Cognitive test assessing episodic memory. Boxes are displayed on the screen and are "opened" in a randomized order. One or more of them contains a pattern. The patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. The number of boxes increases progressively to a total of 8.', 'unitOfMeasure': 'Change from Day 1 in total errors', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.'}, {'type': 'SECONDARY', 'title': 'Spatial Working Memory Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}, {'value': '17', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo oral tablets administered twice daily (BID)'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Simufilam, 100 mg oral tablets administered twice daily (BID)'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Simufilam, 50 mg oral tablets administered twice daily (BID)'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.41', 'spread': '7.54', 'groupId': 'OG000'}, {'value': '-2.31', 'spread': '7.45', 'groupId': 'OG001'}, {'value': '-3.35', 'spread': '4.86', 'groupId': 'OG002'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Effect size', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.46', 'estimateComment': "Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was almost identical (0.45) when calculated by Cohen's d.", 'groupDescription': 'This study was not powered for statistical significance on cognitive measures.', 'nonInferiorityType': 'OTHER'}, {'groupIds': ['OG000', 'OG002'], 'paramType': 'Effect size', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.25', 'estimateComment': "Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was identical when calculated by Cohen's d.", 'groupDescription': 'This study was not powered for statistical significance on cognitive measures.', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 28', 'description': "Cognitive assessment of spatial working memory: A number of colored squares (boxes) are shown on the screen. By selecting the boxes and using a process of elimination, the subject should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The number of boxes is gradually increased to a total of 8 for the subjects to search. The colors and positions of the boxes are changed from trial to trial to discourage stereotyped search strategies.", 'unitOfMeasure': 'Change from Day 1 in total errors', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Removed from analysis were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.'}, {'type': 'SECONDARY', 'title': 'CSF IL-6, sTREM2, HMGB1, Albumin, IgG', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '19', 'groupId': 'OG001'}, {'value': '18', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo oral tablets administered twice daily (BID)'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Simufilam, 100 mg oral tablets administered twice daily (BID)'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Simufilam, 50 mg oral tablets administered twice daily (BID)'}], 'classes': [{'title': 'CSF IL-6', 'categories': [{'measurements': [{'value': '-1.1', 'spread': '2.0', 'groupId': 'OG000'}, {'value': '-3.7', 'spread': '1.8', 'groupId': 'OG001'}, {'value': '-3.3', 'spread': '1.9', 'groupId': 'OG002'}]}]}, {'title': 'CSF sTREM2', 'categories': [{'measurements': [{'value': '-77.3', 'spread': '510', 'groupId': 'OG000'}, {'value': '-426', 'spread': '274', 'groupId': 'OG001'}, {'value': '-424', 'spread': '386', 'groupId': 'OG002'}]}]}, {'title': 'CSF HMGB1', 'categories': [{'measurements': [{'value': '19.4', 'spread': '172.3', 'groupId': 'OG000'}, {'value': '-143', 'spread': '51.3', 'groupId': 'OG001'}, {'value': '-152', 'spread': '50.1', 'groupId': 'OG002'}]}]}, {'title': 'CSF albumin', 'categories': [{'measurements': [{'value': '-240', 'spread': '1620', 'groupId': 'OG000'}, {'value': '-2292', 'spread': '1760', 'groupId': 'OG001'}, {'value': '-1245', 'spread': '1735', 'groupId': 'OG002'}]}]}, {'title': 'CSF IgG', 'categories': [{'measurements': [{'value': '-574.8', 'spread': '2518', 'groupId': 'OG000'}, {'value': '-2350', 'spread': '2517', 'groupId': 'OG001'}, {'value': '-2444', 'spread': '2097', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.0078', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for IL-6.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.019', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for IL-6.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.0002', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for sTREM2.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.0007', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for sTREM2.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.0001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for HMGB1.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.0001', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for HMGB1.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.0001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for albumin.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.046', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for albumin.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.012', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for Immunoglobulin G.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}, {'pValue': '0.014', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'Secondary CSF biomarkers were not adjusted for multiplicity.', 'groupDescription': 'This analysis is for Immunoglobulin G.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.'}], 'paramType': 'MEAN', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening sample) to Day 28 in secondary CSF biomarkers of neuroinflammation and blood-brain barrier integrity', 'unitOfMeasure': 'pg/mL; optical density for albumin & IgG', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Three subjects who had no detectable simufilam in plasma at return visits were removed from analyses (two in the 100 mg arm and one in the 50 mg arm). As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Target Engagement Assays: Change From Baseline in Filamin A (FLNA) Linkages to alpha7 Nicotinic Acetylcholine Receptor (alpha7nAChR) and Toll-like Receptor 4 (TLR4) in Subject Lymphocytes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '19', 'groupId': 'OG001'}, {'value': '17', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Placebo oral tablets administered twice daily (BID)'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Simufilam, 100 mg oral tablets administered twice daily (BID)'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Simufilam, 50 mg oral tablets administered twice daily (BID)'}], 'classes': [{'title': 'FLNA - alpha7nAChR linkage', 'categories': [{'measurements': [{'value': '-0.07', 'spread': '0.19', 'groupId': 'OG000'}, {'value': '-0.24', 'spread': '0.16', 'groupId': 'OG001'}, {'value': '-0.23', 'spread': '0.13', 'groupId': 'OG002'}]}]}, {'title': 'FLNA - TLR4 linkage', 'categories': [{'measurements': [{'value': '-0.05', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '-0.19', 'spread': '0.14', 'groupId': 'OG001'}, {'value': '-0.19', 'spread': '0.11', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.005', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.', 'groupDescription': 'Change from baseline in FLNA linkage to alpha7nAChR in subject lymphocytes. FLNA linkage to alpha7nAChR was expressed as the ratio of densitometric units of immunoblot bands of alpha7nAChR (probed with a specific antibody) to densitometric units of total FLNA.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value."}, {'pValue': '0.009', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.', 'groupDescription': 'Change from baseline in FLNA linkage to alpha7nAChR in subject lymphocytes. FLNA linkage to alpha7nAChR was expressed as ratios of densitometric units of immunoblot bands of alpha7nAChR (probed with a specific antibody) to densitometric units of total FLNA.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value."}, {'pValue': '0.01', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.', 'groupDescription': 'Change from baseline in FLNA linkage to TLR4 in subject lymphocytes. FLNA linkage to TLR4 was expressed as the ratio of densitometric units of immunoblot bands of TLR4 (probed with a specific antibody) to densitometric units of total FLNA.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value."}, {'pValue': '0.01', 'groupIds': ['OG000', 'OG002'], 'pValueComment': 'As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.', 'groupDescription': 'Change from baseline in FLNA linkage to TLR4 in subject lymphocytes. FLNA linkage to TLR4 was expressed as the ratio of densitometric units of immunoblot bands of TLR4 (probed with a specific antibody) to densitometric units of total FLNA.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value."}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 28', 'description': 'FLNA linkages to these two receptors were assessed by densitometric quantitation of immunoblot bands of each receptor (detected by a specific antibody) in anti-FLNA precipitates. The measure is noted as a ratio to total FLNA.', 'unitOfMeasure': 'ratio to total FLNA', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Three subjects who had no detectable simufilam in plasma at any return visit were removed from analyses (two in the 100 mg arm and one in the 50 mg arm). As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. Two additional subjects in the 50 mg arm were missing Day 1 blood samples.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Plasma P-tau181', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}, {'value': '15', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Subjects administered placebo oral tablets twice daily (BID)\n\nPlacebo oral tablet: Oral placebo tablet'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125) 100 mg Tablets Cohort', 'description': 'Subjects administered simufilam (PTI-125) 100 mg oral tablets twice daily (BID)\n\nSimufilam 50 mg oral tablet: Simufilam 50 mg oral tablet'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125) 50 mg Tablets Cohort', 'description': 'Subjects administered simufilam (PTI-125) 50 mg oral tablets twice daily (BID)\n\nSimufilam 100 mg tablet: Simufilam 100 mg oral tablet'}], 'classes': [{'categories': [{'measurements': [{'value': '20.7', 'spread': '49', 'groupId': 'OG000'}, {'value': '-16.5', 'spread': '29', 'groupId': 'OG001'}, {'value': '-15.1', 'spread': '36', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.01', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "ANOVA followed by Dunnett's multiple comparisons test."}, {'pValue': '0.02', 'groupIds': ['OG000', 'OG002'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "ANOVA followed by Dunnett's multiple comparisons test."}, {'pValue': '0.009', 'groupIds': ['OG000', 'OG001', 'OG002'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'This p value is for the main effect of treatment of the ANOVA.'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 28', 'description': 'Percent change in plasma P-tau181', 'unitOfMeasure': 'Percent change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'For plasma p-tau181 only: 4 subjects (1 in placebo, 2 in 50 mg and 1 in 100 mg arms) were removed because Coefficients of Variation (CVs) between duplicate measurements for either Day 1 or Day 28 samples were \\>15% on repeat assay (both Day 1 \\& Day 28 for a subject were repeated if CVs of either Day 1 or Day 28 were \\>11%). Two outliers were removed (1 in placebo \\[1.2 to 4.8 pg/ml\\] and 1 in 100 mg \\[2.1 to 5.1 pg/ml\\] arms) for increases \\>150% \\& \\> 2.5 pg/mL. Missing Day 1 blood samples: 2 in 50 mg.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '19', 'groupId': 'OG001'}, {'value': '17', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Cohort', 'description': 'Subjects administered placebo oral tablets twice daily (BID)'}, {'id': 'OG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Subjects administered simufilam 100 mg oral tablets twice daily (BID)'}, {'id': 'OG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Subjects administered simufilam 50 mg oral tablets twice daily (BID)'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.2', 'spread': '62', 'groupId': 'OG000'}, {'value': '-47.8', 'spread': '19', 'groupId': 'OG001'}, {'value': '-44.1', 'spread': '35', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.003', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.016', 'groupIds': ['OG000', 'OG002'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 to Day 28', 'description': 'SavaDx is a novel plasma biomarker', 'unitOfMeasure': 'Percent change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'One subject in the 50 mg arm and two subjects in the 100 mg arm were omitted because these subjects showed no detectable plasma simufilam at any return visit. Two additional subjects in the 50 mg group were missing baseline plasma samples.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo Cohort', 'description': 'Subjects administered placebo oral tablets twice daily (BID)'}, {'id': 'FG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Subjects administered simufilam 100 mg oral tablets twice daily (BID)'}, {'id': 'FG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Subjects administered simufilam 50 mg oral tablets twice daily (BID)'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '22'}, {'groupId': 'FG001', 'numSubjects': '21'}, {'groupId': 'FG002', 'numSubjects': '21'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '22'}, {'groupId': 'FG001', 'numSubjects': '21'}, {'groupId': 'FG002', 'numSubjects': '20'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo Cohort', 'description': 'Subjects administered matching placebo tablets twice daily for 28 days.'}, {'id': 'BG001', 'title': 'Simufilam (PTI-125), 100 mg Tablets Cohort', 'description': 'Subjects administered 100 mg simufilam tablets twice daily for 28 days.'}, {'id': 'BG002', 'title': 'Simufilam (PTI-125), 50 mg Tablets Cohort', 'description': 'Subjects administered 50 mg simufilam tablets twice daily for 28 days.'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}, {'value': '19', 'groupId': 'BG003'}]}, {'title': '>=65 years', 'measurements': [{'value': '18', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}, {'value': '45', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '71.3', 'spread': '6.68', 'groupId': 'BG000'}, {'value': '69.3', 'spread': '5.47', 'groupId': 'BG001'}, {'value': '67.1', 'spread': '8.76', 'groupId': 'BG002'}, {'value': '69.2', 'spread': '6.97', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}, {'value': '35', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '29', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}, {'value': '31', 'groupId': 'BG003'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}, {'value': '33', 'groupId': 'BG003'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}, {'value': '8', 'groupId': 'BG003'}]}, {'title': 'White', 'measurements': [{'value': '19', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}, {'value': '55', 'groupId': 'BG003'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'CSF total tau/Aβ42 ratio', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '1.20', 'spread': '0.55', 'groupId': 'BG000'}, {'value': '1.08', 'spread': '0.50', 'groupId': 'BG001'}, {'value': '1.17', 'spread': '0.58', 'groupId': 'BG002'}, {'value': '1.15', 'spread': '0.54', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ratio', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Mini-Mental State Exam (MMSE)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '23.1', 'spread': '2.78', 'groupId': 'BG000'}, {'value': '23.0', 'spread': '2.66', 'groupId': 'BG001'}, {'value': '22.7', 'spread': '2.67', 'groupId': 'BG002'}, {'value': '22.9', 'spread': '2.70', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': "The MMSE is a is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language and visual-spatial skills. It is often used to stage Alzheimer's disease. The scale ranges from 0 to 30. No errors = 30.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Taking cholinesterase inhibitor or memantine', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}, {'value': '20', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Heterozygous APOE4', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '35', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Homozygous APOE4', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '5', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Paired Associates Learning total errors', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}, {'value': '37', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '35.5', 'spread': '19.65', 'groupId': 'BG000'}, {'value': '31.0', 'spread': '20.74', 'groupId': 'BG001'}, {'value': '36.1', 'spread': '18.76', 'groupId': 'BG002'}, {'value': '34.2', 'spread': '19.7', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': 'Boxes are displayed on the screen and are "opened" in a randomized order. One or more of them contains a pattern. The patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. The number of boxes increases progressively to a total of 8.', 'unitOfMeasure': 'errors', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.'}, {'title': 'Spatial Working Memory total errors', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}, {'value': '57', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '19.0', 'spread': '7.49', 'groupId': 'BG000'}, {'value': '22.1', 'spread': '5.88', 'groupId': 'BG001'}, {'value': '22.3', 'spread': '6.64', 'groupId': 'BG002'}, {'value': '21.1', 'spread': '6.67', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': "A number of colored squares (boxes) are shown on the screen. By selecting the boxes and using a process of elimination, the subject should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The number of boxes is gradually increased to a total of 8 for the subjects to search. The colors and positions of the boxes are changed from trial to trial to discourage stereotyped search strategies.", 'unitOfMeasure': 'errors', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Removed from analysis were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes'}, {'title': 'CSF Aβ42', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '125', 'spread': '152', 'groupId': 'BG000'}, {'value': '117', 'spread': '51.4', 'groupId': 'BG001'}, {'value': '108', 'spread': '54.8', 'groupId': 'BG002'}, {'value': '111', 'spread': '86.1', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF total tau', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '104', 'spread': '32', 'groupId': 'BG000'}, {'value': '106', 'spread': '27.9', 'groupId': 'BG001'}, {'value': '101', 'spread': '17.6', 'groupId': 'BG002'}, {'value': '103.7', 'spread': '25.8', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF P-tau181', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '28.5', 'spread': '0.73', 'groupId': 'BG000'}, {'value': '29.7', 'spread': '1.5', 'groupId': 'BG001'}, {'value': '29.0', 'spread': '1.0', 'groupId': 'BG002'}, {'value': '29.1', 'spread': '1.3', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF neurogranin', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '1200', 'spread': '365', 'groupId': 'BG000'}, {'value': '1551', 'spread': '751', 'groupId': 'BG001'}, {'value': '1352', 'spread': '614', 'groupId': 'BG002'}, {'value': '1368', 'spread': '577', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF Neurofilament Light Chain', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '161', 'spread': '42.8', 'groupId': 'BG000'}, {'value': '219', 'spread': '95.3', 'groupId': 'BG001'}, {'value': '181', 'spread': '64.4', 'groupId': 'BG002'}, {'value': '187', 'spread': '67.5', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF YKL-40', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '206', 'spread': '29.5', 'groupId': 'BG000'}, {'value': '203', 'spread': '22.7', 'groupId': 'BG001'}, {'value': '194', 'spread': '26.0', 'groupId': 'BG002'}, {'value': '201', 'spread': '26.1', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF IL-6', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '32.5', 'spread': '1.2', 'groupId': 'BG000'}, {'value': '33.6', 'spread': '1.8', 'groupId': 'BG001'}, {'value': '33.6', 'spread': '1.7', 'groupId': 'BG002'}, {'value': '33.2', 'spread': '1.6', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF sTREM2', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '878', 'spread': '435', 'groupId': 'BG000'}, {'value': '861', 'spread': '421', 'groupId': 'BG001'}, {'value': '882', 'spread': '476', 'groupId': 'BG002'}, {'value': '874', 'spread': '444', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF HMGB1', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '424', 'spread': '48.0', 'groupId': 'BG000'}, {'value': '446', 'spread': '67.3', 'groupId': 'BG001'}, {'value': '454', 'spread': '70.6', 'groupId': 'BG002'}, {'value': '441', 'spread': '62.0', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF/plasma albumin ratio', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0.24', 'spread': '0.03', 'groupId': 'BG000'}, {'value': '0.25', 'spread': '0.08', 'groupId': 'BG001'}, {'value': '0.25', 'spread': '0.05', 'groupId': 'BG002'}, {'value': '0.25', 'spread': '0.05', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ratio', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'CSF/plasma IgG ratio', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0.200', 'spread': '0.07', 'groupId': 'BG000'}, {'value': '0.217', 'spread': '0.11', 'groupId': 'BG001'}, {'value': '0.227', 'spread': '0.07', 'groupId': 'BG002'}, {'value': '0.215', 'spread': '0.08', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ratio', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'Lymphocyte filamin A - α7nAChR, Ratio to total filamin A', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0.59', 'spread': '0.10', 'groupId': 'BG000'}, {'value': '0.69', 'spread': '0.11', 'groupId': 'BG001'}, {'value': '0.66', 'spread': '0.12', 'groupId': 'BG002'}, {'value': '0.65', 'spread': '0.11', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ratio', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}, {'title': 'Lymphocyte filamin A - TLR4, Ratio to total filamin A', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0.55', 'spread': '0.10', 'groupId': 'BG000'}, {'value': '0.60', 'spread': '0.07', 'groupId': 'BG001'}, {'value': '0.58', 'spread': '0.11', 'groupId': 'BG002'}, {'value': '0.58', 'spread': '0.09', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ratio', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-06-28', 'size': 922764, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2021-03-30T14:49', 'hasProtocol': True}, {'date': '2020-02-12', 'size': 797246, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_003.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2021-05-06T10:10', 'hasProtocol': False}, {'date': '2019-07-10', 'size': 292711, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_002.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2021-03-30T14:56', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'The sponsor, participant, care provider, investigator including sub-investigators and outcomes assessors will be blinded to throughout the study which includes using an Integrated Web Response System (IWRS) and electronic data capture (EDC) to ensure blinding during the study.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Approximately sixty (60) patients will be enrolled into the study and randomized to one of three cohorts. Cohorts will receive placebo or PTI-125 at 50 or 100 mg b.i.d. (n=20 per group)'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 64}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-09-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-09', 'completionDateStruct': {'date': '2020-03-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-09-07', 'studyFirstSubmitDate': '2019-08-26', 'resultsFirstSubmitDate': '2021-04-12', 'studyFirstSubmitQcDate': '2019-09-04', 'lastUpdatePostDateStruct': {'date': '2021-09-29', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-05-06', 'studyFirstPostDateStruct': {'date': '2019-09-06', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2021-06-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-03-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Target Engagement Assays: Change From Baseline in Filamin A (FLNA) Linkages to alpha7 Nicotinic Acetylcholine Receptor (alpha7nAChR) and Toll-like Receptor 4 (TLR4) in Subject Lymphocytes', 'timeFrame': 'Day 1 to Day 28', 'description': 'FLNA linkages to these two receptors were assessed by densitometric quantitation of immunoblot bands of each receptor (detected by a specific antibody) in anti-FLNA precipitates. The measure is noted as a ratio to total FLNA.'}, {'measure': 'Plasma P-tau181', 'timeFrame': 'Day 1 to Day 28', 'description': 'Percent change in plasma P-tau181'}, {'measure': 'Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker', 'timeFrame': 'Day 1 to Day 28', 'description': 'SavaDx is a novel plasma biomarker'}], 'primaryOutcomes': [{'measure': 'Change From Baseline in CSF Abeta42', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42'}, {'measure': 'Change From Baseline in CSF Total Tau.', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.'}, {'measure': 'Change From Baseline in CSF P-tau181', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181'}, {'measure': 'Change From Baseline in CSF Neurogranin', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin'}, {'measure': 'Change From Baseline in CSF Neurofilament Light Chain', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain'}, {'measure': 'Change From Baseline in CSF YKL-40', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening) in cerebrospinal fluid YKL-40'}], 'secondaryOutcomes': [{'measure': 'Paired Associates Learning Test', 'timeFrame': 'Day 1 to Day 28', 'description': 'Cognitive test assessing episodic memory. Boxes are displayed on the screen and are "opened" in a randomized order. One or more of them contains a pattern. The patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. The number of boxes increases progressively to a total of 8.'}, {'measure': 'Spatial Working Memory Test', 'timeFrame': 'Day 1 to Day 28', 'description': "Cognitive assessment of spatial working memory: A number of colored squares (boxes) are shown on the screen. By selecting the boxes and using a process of elimination, the subject should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The number of boxes is gradually increased to a total of 8 for the subjects to search. The colors and positions of the boxes are changed from trial to trial to discourage stereotyped search strategies."}, {'measure': 'CSF IL-6, sTREM2, HMGB1, Albumin, IgG', 'timeFrame': 'Screening to Day 28', 'description': 'Change from Baseline (screening sample) to Day 28 in secondary CSF biomarkers of neuroinflammation and blood-brain barrier integrity'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Alzheimer Disease']}, 'referencesModule': {'references': [{'pmid': '33188449', 'type': 'DERIVED', 'citation': 'Sever S. Role of actin cytoskeleton in podocytes. Pediatr Nephrol. 2021 Sep;36(9):2607-2614. doi: 10.1007/s00467-020-04812-z. Epub 2020 Nov 13.'}], 'seeAlsoLinks': [{'url': 'http://nnjournal.net/article/view/2313', 'label': "Altered filamin A enables amyloid beta-induced tau hyperphosphorylation and neuroinflammation in Alzheimer's disease"}]}, 'descriptionModule': {'briefSummary': "This is a Phase 2b, Randomized, Double-blind, Placebo-controlled, multiple dose study of PTI-125 in mild-to-moderate Alzheimer's disease patients.", 'detailedDescription': "This is a Phase 2b, Randomized, Double-blind, Placebo-controlled, multiple dose study of PTI-125 in mild-to-moderate Alzheimer's disease patients. A total of sixty (60) patients will be enrolled in the study. Patients will receive Placebo, 50 mg or 100 mg b.i.d. of PTI-125. The objective of this study are to investigate the safety, and biomarkers of PTI-125 following 28-day repeat oral administration."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '50 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Ages \\>= 50 and \\<= 85 years\n* Informed consent form (ICF) signed by the subject or legally acceptable representative.\n* Clinical diagnosis of dementia due to possible or probable Alzheimer's disease\n* Mini-Mental State Examination score \\>= 16 and \\<= 26 at screening\n* If female, postmenopausal for at least 1 year\n* Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-h) nursing care\n* General health status acceptable for participation in the study\n* Fluency (oral and written) in English or Spanish\n* If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months. If receiving donepezil, any dose lower than 23 mg once daily.\n* The patient is a non-smoker for at least 3 years.\n* The patient or legal representative must agree to comply with the drawing of blood samples and with a lumbar puncture and the drawing of cerebrospinal fluid samples.\n* The patient has a ratio of total tau/Aβ42 in cerebrospinal fluid \\>= 0.28.\n* Patient has a caregiver or legal representative responsible for administering the drug and recording the time.\n\nExclusion Criteria:\n\n* Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening\n* Enrollment in the previous PTI-125 trial\n* A medical condition that would interfere with a lumbar puncture\n* Residence in a skilled nursing facility and requiring 24 h care.\n* Clinically significant laboratory test results\n* Clinically significant untreated hypothyroidism\n* Insufficiently controlled diabetes mellitus\n* Renal insufficiency (serum creatinine \\> ULN)\n* Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer or localized stage 1 bladder cancer)\n* History of ischemic colitis or ischemic enterocolitis\n* Unstable medical condition that is clinically significant in the judgment of the investigator\n* Alanine transaminase (ALT) or aspartate transaminase (AST) \\> ULN or total bilirubin \\> ULN.\n* History of myocardial infarction or unstable angina within 6 months before screening\n* History of more than 1 myocardial infarction within 5 years before screening\n* Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)\n* Symptomatic hypotension, or uncontrolled hypertension\n* Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT interval value \\>= 450 msec for males or \\>= 470 msec for females.\n* Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia\n* History of brain tumor or other clinically significant space-occupying lesion on CT or MRI\n* Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia\n* Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation\n* Specific degenerative Central Nervous System disease diagnosis other than Alzheimer's disease (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)\n* Wernicke's encephalopathy\n* Active acute or chronic Central Nervous System infection\n* Donepezil 23 mg quaque die currently or within 3 months prior to randomization\n* Discontinued AChEI \\< 30 days prior to randomization\n* Antipsychotics; low doses are allowed only if the subject has received a stable dose for at least 3 months before randomization\n* Tricyclic antidepressants and monoamine oxidase inhibitors\n* Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed\n* Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)\n* Antiepileptic medications if taken for control of seizures\n* Chronic intake of opioid-containing analgesics\n* Sedating H1 antihistamines\n* Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening\n* Clinically significant illness within 30 days of enrollment\n* History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease\n* Positive serum hepatitis B surface antigen (HBsAg) or positive hepatitis C virus HCV antibody test at screening\n* Positive HIV test at screening\n* Positive urine drug test at screening\n* Loss of a significant volume of blood (\\> 450 mL) within 4 weeks prior to the study\n* Suicidality on C-SSRS at screening"}, 'identificationModule': {'nctId': 'NCT04079803', 'briefTitle': "PTI-125 for Mild-to-moderate Alzheimer's Disease Patients", 'organization': {'class': 'INDUSTRY', 'fullName': 'Cassava Sciences, Inc.'}, 'officialTitle': "A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multiple Dose, Biomarker and Safety Study of PTI-125 in Mild-to-moderate Alzheimer's Disease Patients", 'orgStudyIdInfo': {'id': 'PTI-125-02'}, 'secondaryIdInfos': [{'id': 'R44AG060878', 'link': 'https://reporter.nih.gov/quickSearch/R44AG060878', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo Cohort', 'description': 'Subjects administered placebo oral tablets twice daily (BID)', 'interventionNames': ['Drug: Placebo oral tablet']}, {'type': 'EXPERIMENTAL', 'label': 'Simufilam (PTI-125) 100 mg tablets Cohort', 'description': 'Subjects administered simufilam (PTI-125) 100 mg oral tablets twice daily (BID)', 'interventionNames': ['Drug: Simufilam 50 mg oral tablet']}, {'type': 'EXPERIMENTAL', 'label': 'Simufilam (PTI-125) 50 mg tablets Cohort', 'description': 'Subjects administered simufilam (PTI-125) 50 mg oral tablets twice daily (BID)', 'interventionNames': ['Drug: Simufilam 100 mg tablet']}], 'interventions': [{'name': 'Placebo oral tablet', 'type': 'DRUG', 'description': 'Oral placebo tablet', 'armGroupLabels': ['Placebo Cohort']}, {'name': 'Simufilam 100 mg tablet', 'type': 'DRUG', 'otherNames': ['PTI-125'], 'description': 'Simufilam 100 mg oral tablet', 'armGroupLabels': ['Simufilam (PTI-125) 50 mg tablets Cohort']}, {'name': 'Simufilam 50 mg oral tablet', 'type': 'DRUG', 'otherNames': ['PTI-125'], 'description': 'Simufilam 50 mg oral tablet', 'armGroupLabels': ['Simufilam (PTI-125) 100 mg tablets Cohort']}]}, 'contactsLocationsModule': {'locations': [{'zip': '85296', 'city': 'Gilbert', 'state': 'Arizona', 'country': 'United States', 'facility': 'Cognitive Clinical Trials', 'geoPoint': {'lat': 33.35283, 'lon': -111.78903}}, {'zip': '85374', 'city': 'Surprise', 'state': 'Arizona', 'country': 'United States', 'facility': 'Cognitive Clinical Trials', 'geoPoint': {'lat': 33.63059, 'lon': -112.33322}}, {'zip': '33125', 'city': 'Miami', 'state': 'Florida', 'country': 'United States', 'facility': 'Optimus U', 'geoPoint': {'lat': 25.77427, 'lon': -80.19366}}, {'zip': '33157', 'city': 'Palmetto Bay', 'state': 'Florida', 'country': 'United States', 'facility': 'IMIC, Inc.', 'geoPoint': {'lat': 25.62177, 'lon': -80.32477}}, {'zip': '68005', 'city': 'Bellevue', 'state': 'Nebraska', 'country': 'United States', 'facility': 'Cognitive Clinical Trials', 'geoPoint': {'lat': 41.13667, 'lon': -95.89084}}, {'zip': '68116', 'city': 'Omaha', 'state': 'Nebraska', 'country': 'United States', 'facility': 'Cognitive Clinical Trials', 'geoPoint': {'lat': 41.25626, 'lon': -95.94043}}, {'zip': '08755', 'city': 'Toms River', 'state': 'New Jersey', 'country': 'United States', 'facility': 'Advanced Memory Research Institute', 'geoPoint': {'lat': 39.95373, 'lon': -74.19792}}, {'zip': '77058', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Centex Studies, Inc.', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '78504', 'city': 'McAllen', 'state': 'Texas', 'country': 'United States', 'facility': 'Centex Studies, Inc.', 'geoPoint': {'lat': 26.20341, 'lon': -98.23001}}], 'overallOfficials': [{'name': 'Lindsay Burns, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Cassava Sciences, Inc.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Cassava Sciences, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'National Institute on Aging (NIA)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}