Ignite Creation Date:
2025-12-24 @ 12:48 PM
Ignite Modification Date:
2025-12-28 @ 12:29 PM
Study NCT ID:
NCT04659161
Status:
COMPLETED
Last Update Posted:
2023-12-12
First Post:
2020-12-02
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-2)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2023-11-18', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D012559', 'term': 'Schizophrenia'}, {'id': 'D011618', 'term': 'Psychotic Disorders'}], 'ancestors': [{'id': 'D019967', 'term': 'Schizophrenia Spectrum and Other Psychotic Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C075257', 'term': 'xanomeline'}, {'id': 'C003330', 'term': 'trospium chloride'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'medinfo@karunatx.com', 'phone': '1-888-783-0380', 'title': 'Inder Kaul, VP Clinical Development', 'organization': 'Karuna Therapeutics, Inc.'}, 'certainAgreement': {'restrictionType': 'GT60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From the start of study drug administration up to Week 5.', 'description': 'The Safety population included all participants who received at least one dose of study medication.', 'eventGroups': [{'id': 'EG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.', 'otherNumAtRisk': 126, 'deathsNumAtRisk': 126, 'otherNumAffected': 95, 'seriousNumAtRisk': 126, 'deathsNumAffected': 0, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.', 'otherNumAtRisk': 125, 'deathsNumAtRisk': 125, 'otherNumAffected': 73, 'seriousNumAtRisk': 125, 'deathsNumAffected': 0, 'seriousNumAffected': 2}], 'otherEvents': [{'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 27}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 13}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 24}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 10}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 24}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 7}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 18}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Abdominal discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Dry mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Gastrooesophageal reflux disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Toothache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 17}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 15}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 11}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 4}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 5}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 5}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Agitation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 8}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 6}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Psychotic disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 6}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 12}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Orthostatic hypotension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Heart rate increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 5}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 3}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Vision blurred', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 0}], 'organSystem': 'Eye disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Salivary hypersecretion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Tachycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 3}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}], 'seriousEvents': [{'term': 'Appendicitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Suicidal ideation', 'notes': 'Suicidal ideation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}, {'term': 'Schizophrenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 126, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 125, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 23.1'}], 'frequencyThreshold': '2'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'OG000'}, {'value': '119', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '-21.2', 'spread': '1.652', 'groupId': 'OG000'}, {'value': '-11.6', 'spread': '1.600', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS mean difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-9.6', 'ciLowerLimit': '-13.9', 'ciUpperLimit': '-5.2', 'statisticalMethod': 'Mixed Model for Repeated Measures', 'nonInferiorityType': 'SUPERIORITY', 'otherAnalysisDescription': 'Statistics are from a mixed model for repeated measures (MMRM). The model includes the treatment group (KarXT or placebo), visit, and the interaction between the treatment group and visit as fixed factors, and baseline PANSS total score, site, age, and gender as covariates. An unstructured covariance matrix is used to model the correlation among repeated measurements and the denominator degrees of freedom are computed using the Kenward-Roger method.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The Modified Intent-to-Treat (MITT) population included all participants who were randomized, received at least one dose of study medication, and had a baseline and at least one post-baseline PANSS assessment. Here, the number of participants analyzed indicates participants who were evaluable for this measure at given time points for each group.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'OG000'}, {'value': '119', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '-6.8', 'spread': '0.526', 'groupId': 'OG000'}, {'value': '-3.9', 'spread': '0.512', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Mixed Model for Repeated Measures', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. For positive symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The Modified Intent-to-Treat (MITT) population included all participants who were randomized, received at least one dose of study medication, and had a baseline and at least one post-baseline PANSS assessment. Here, the number of participants analyzed indicates participants who were evaluable for this measure at given time points for each group.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'OG000'}, {'value': '119', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.4', 'spread': '0.479', 'groupId': 'OG000'}, {'value': '-1.6', 'spread': '0.466', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0055', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Mixed Model Repeated Measures', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. For negative symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The Modified Intent-to-Treat (MITT) population included all participants who were randomized, received at least one dose of study medication, and had a baseline and at least one post-baseline PANSS assessment. Here, the number of participants analyzed indicates participants who were evaluable for this measure at given time points for each group.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'OG000'}, {'value': '119', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '-4.2', 'spread': '0.530', 'groupId': 'OG000'}, {'value': '-2.0', 'spread': '0.517', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0022', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Mixed Model for Repeated Measures', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 5', 'description': 'The Marder Factor Negative Score is derived from the Positive and Negative Syndrome Scale (PANSS) and consists of the sum of 5 negative scales (N) and 2 general scales (G) (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance), with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'The Modified Intent-to-Treat (MITT) population included all participants who were randomized, received at least one dose of study medication, and had a baseline and at least one post-baseline PANSS assessment. Here, the number of participants analyzed indicates participants who were evaluable for this measure at given time points for each group.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline Clinical Global Impression - Severity (CGI-S) Score at Week 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'OG000'}, {'value': '119', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.2', 'spread': '0.103', 'groupId': 'OG000'}, {'value': '-0.7', 'spread': '0.099', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Mixed Model for Repeated Measures', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 5', 'description': 'The CGI-S modified asked the clinician 1 question: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician\'s answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'The Modified Intent-to-Treat (MITT) population included all participants who were randomized, received at least one dose of study medication, and had a baseline and at least one post-baseline PANSS assessment. Here, the number of participants analyzed indicates participants who were evaluable for this measure at given time points for each group.'}, {'type': 'SECONDARY', 'title': 'Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in PANSS Total Score) at Week 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '93', 'groupId': 'OG000'}, {'value': '99', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '51', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Mixed Model for Repeated Measures', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 5.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The Modified Intent-to-Treat (MITT) population included all participants who were randomized, received at least one dose of study medication, and had a baseline and at least one post-baseline PANSS assessment. Here, the number of participants analyzed indicates participants who were evaluable for this measure at given time points for each group. The overall number of participants was analyzed (N) = number of subjects with Week 5 score.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '126'}, {'groupId': 'FG001', 'numSubjects': '126'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '94'}, {'groupId': 'FG001', 'numSubjects': '100'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '32'}, {'groupId': 'FG001', 'numSubjects': '26'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'Other', 'reasons': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '8'}]}]}], 'recruitmentDetails': 'The study was conducted in 21 study centers in the United States.', 'preAssignmentDetails': 'A total of 407 participants were screened, 252 were randomized, and 251 participants were treated.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '126', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'KarXT', 'description': 'Participants received oral capsule KarXT (xanomeline/trospium chloride BID) in a treatment period of 5 weeks. Participants were started on a lead in dose of xanomeline 50 mg/trospium chloride 20 mg twice a day (BID) for the first 2 days followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the Participant was continuing to experience adverse events from the previous dose increase of xanomeline 100 mg/trospium chloride 20 mg BID. All Participants who were increased to xanomeline 125 mg/trospium chloride 30 mg BID, depending on clinical response and tolerability, had the option to return to xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of the treatment period.'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Participants received the matching placebo to KarXT orally twice daily for a treatment period of 5 weeks.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '126', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '45.6', 'spread': '10.42', 'groupId': 'BG000'}, {'value': '46.2', 'spread': '10.78', 'groupId': 'BG001'}, {'value': '45.9', 'spread': '10.58', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '126', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '31', 'groupId': 'BG000'}, {'value': '31', 'groupId': 'BG001'}, {'value': '62', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '95', 'groupId': 'BG000'}, {'value': '95', 'groupId': 'BG001'}, {'value': '190', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '126', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '111', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '225', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '126', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Black or African American', 'measurements': [{'value': '97', 'groupId': 'BG000'}, {'value': '92', 'groupId': 'BG001'}, {'value': '189', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '26', 'groupId': 'BG000'}, {'value': '31', 'groupId': 'BG001'}, {'value': '57', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Other', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '126', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '126', 'groupId': 'BG000'}, {'value': '126', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Baseline PANSS Total Score', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '125', 'groupId': 'BG001'}, {'value': '251', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '98.3', 'spread': '8.93', 'groupId': 'BG000'}, {'value': '97.9', 'spread': '9.71', 'groupId': 'BG001'}, {'value': '98.1', 'spread': '9.31', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Measure Analysis Population Description: A total of 252 subjects were randomized (126 subjects in each group) at 21 sites, and a total of 251 subjects were treated (126 \\[100.0%\\] in the KarXT group and 125 \\[99.2%\\] in the placebo group) during the study.'}, {'title': 'Baseline PANSS Positive Score', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '125', 'groupId': 'BG001'}, {'value': '251', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '26.8', 'spread': '3.74', 'groupId': 'BG000'}, {'value': '26.7', 'spread': '3.97', 'groupId': 'BG001'}, {'value': '26.7', 'spread': '3.85', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Measure Analysis Population Description: A total of 252 subjects were randomized (126 subjects in each group) at 21 sites, and a total of 251 subjects were treated (126 \\[100.0%\\] in the KarXT group and 125 \\[99.2%\\] in the placebo group) during the study.'}, {'title': 'Baseline PANSS Negative Score', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '125', 'groupId': 'BG001'}, {'value': '251', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '22.9', 'spread': '4.00', 'groupId': 'BG000'}, {'value': '22.9', 'spread': '3.82', 'groupId': 'BG001'}, {'value': '22.9', 'spread': '3.90', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Measure Analysis Population Description: A total of 252 subjects were randomized (126 subjects in each group) at 21 sites, and a total of 251 subjects were treated (126 \\[100.0%\\] in the KarXT group and 125 \\[99.2%\\] in the placebo group) during the study.'}, {'title': 'Baseline PANSS General Psychopathology Score', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '125', 'groupId': 'BG001'}, {'value': '251', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '48.6', 'spread': '5.79', 'groupId': 'BG000'}, {'value': '48.4', 'spread': '5.99', 'groupId': 'BG001'}, {'value': '48.5', 'spread': '5.88', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Measure Analysis Population Description: A total of 252 subjects were randomized (126 subjects in each group) at 21 sites, and a total of 251 subjects were treated (126 \\[100.0%\\] in the KarXT group and 125 \\[99.2%\\] in the placebo group) during the study.'}, {'title': 'Baseline PANSS Marder Factor Negative Score', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'BG000'}, {'value': '125', 'groupId': 'BG001'}, {'value': '251', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '22.9', 'spread': '4.97', 'groupId': 'BG000'}, {'value': '22.5', 'spread': '4.73', 'groupId': 'BG001'}, {'value': '22.7', 'spread': '4.85', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'The Marder Factor Negative Score is derived from the Positive and Negative Syndrome Scale (PANSS) and consists of the sum of 5 negative scales (N) and 2 general scales (G) (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance), with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Measure Analysis Population Description: A total of 252 subjects were randomized (126 subjects in each group) at 21 sites, and a total of 251 subjects were treated (126 \\[100.0%\\] in the KarXT group and 125 \\[99.2%\\] in the placebo group) during the study.'}], 'populationDescription': 'The Intent-to-Treat (ITT) population included all participants who were randomized to the study. Participants were analyzed according to randomized treatment.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-08-09', 'size': 5459114, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2023-10-27T06:36', 'hasProtocol': True}, {'date': '2022-06-28', 'size': 2209384, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2023-10-27T06:37', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 252}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-12-16', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-11', 'completionDateStruct': {'date': '2022-05-24', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-11-20', 'studyFirstSubmitDate': '2020-12-02', 'resultsFirstSubmitDate': '2023-10-27', 'studyFirstSubmitQcDate': '2020-12-02', 'lastUpdatePostDateStruct': {'date': '2023-12-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-11-20', 'studyFirstPostDateStruct': {'date': '2020-12-09', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-12-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-05-24', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.'}], 'secondaryOutcomes': [{'measure': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. For positive symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.'}, {'measure': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. For negative symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.'}, {'measure': 'Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Score', 'timeFrame': 'Baseline and Week 5', 'description': 'The Marder Factor Negative Score is derived from the Positive and Negative Syndrome Scale (PANSS) and consists of the sum of 5 negative scales (N) and 2 general scales (G) (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance), with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.'}, {'measure': 'Change From Baseline Clinical Global Impression - Severity (CGI-S) Score at Week 5', 'timeFrame': 'Baseline and Week 5', 'description': 'The CGI-S modified asked the clinician 1 question: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician\'s answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants.'}, {'measure': 'Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in PANSS Total Score) at Week 5', 'timeFrame': 'Baseline and Week 5', 'description': 'The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 5.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Schizophrenia', 'Schizophrenia; Psychosis']}, 'referencesModule': {'references': [{'pmid': '40215379', 'type': 'DERIVED', 'citation': 'Yeung PP, Breier A, Zhu H, Kaul I, Marcus RN. Xanomeline and Trospium Chloride for the Treatment of Agitation Associated With Schizophrenia: PANSS-Excited Component Results From 3 Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials. J Clin Psychiatry. 2025 Mar 24;86(2):24m15668. doi: 10.4088/JCP.24m15668.'}, {'pmid': '40212458', 'type': 'DERIVED', 'citation': 'Citrome L, Neugebauer NM, Meli AA, Kando J. Xanomeline and Trospium Chloride Versus Placebo for the Treatment of Schizophrenia: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed. Neuropsychiatr Dis Treat. 2025 Apr 5;21:761-773. doi: 10.2147/NDT.S503494. eCollection 2025.'}, {'pmid': '40047530', 'type': 'DERIVED', 'citation': 'Kaul I, Claxton A, Sawchak S, Sauder C, Brannan SK, Raj E, Ruan S, Konis G, Brown D, Cutler AJ, Marcus R. Safety and Tolerability of Xanomeline and Trospium Chloride in Schizophrenia: Pooled Results From the 5-Week, Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials. J Clin Psychiatry. 2025 Feb 26;86(1):24m15497. doi: 10.4088/JCP.24m15497.'}, {'pmid': '38104575', 'type': 'DERIVED', 'citation': 'Kaul I, Sawchak S, Correll CU, Kakar R, Breier A, Zhu H, Miller AC, Paul SM, Brannan SK. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet. 2024 Jan 13;403(10422):160-170. doi: 10.1016/S0140-6736(23)02190-6. Epub 2023 Dec 14.'}]}, 'descriptionModule': {'briefSummary': 'This is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter inpatient study to examine the efficacy and safety of KarXT in adult subjects who are acutely psychotic with a Diagnostic and Statistical Manual Fifth Edition (DSM-5) diagnosis of schizophrenia. The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily \\[BID\\]) versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a DSM-5 diagnosis of schizophrenia. The secondary objectives of the study are to evaluate improvement in disease severity and symptoms, safety and tolerability, and pharmacokinetics in adult inpatients with a DSM-5 diagnosis of schizophrenia.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Subject is aged 18 to 65 years, inclusive, at screening.\n2. Subject is capable of providing informed consent.\n\n 1. A signed informed consent form must be provided before any study assessments are performed.\n 2. Subject must be fluent (oral and written) in English to consent\n3. Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.\n4. Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 2 months before screening.\n\n 1. The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms.\n 2. If already an inpatient at screening, has been hospitalized for less than 2 weeks for the current exacerbation at the time of screening.\n5. Positive and Negative Syndrome Scale total score between 80 and 120, inclusive. Score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items:\n\n 1. Item 1 (P1; delusions)\n 2. Item 2 (P2; conceptual disorganization)\n 3. Item 3 (P3; hallucinatory behavior)\n 4. Item 6 (P6; suspiciousness/persecution)\n6. Subjects with no change (improvement) in PANSS total score between screening and baseline (Day -1) of more than 20%.\n7. Subject has a CGI-S score of ≥4 at screening and baseline (Day -1) visits.\n8. Subject will have been off lithium therapy for at least 2 weeks before baseline and free of all oral antipsychotic medications for at least 5 half-lives or 1 week, whichever is longer, before baseline (Day -1).\n9. Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for INVEGA TRINZA) before baseline visit (Day -1).\n10. Subject is willing and able to be confined to an inpatient setting for the study duration, follow instructions, and comply with the protocol requirements.\n11. BMI must be ≥18 and ≤40 kg/m2.\n12. Subject resides in a stable living situation and is anticipated to return to that same stable living situation after discharge, in the opinion of the investigator.\n13. Subject has an identified reliable informant.\n14. Women of childbearing potential, or men with sexual partners of childbearing potential, must be able and willing to use at least 1 highly effective method of contraception during the study and for 30 days after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of study drug.\n\nExclusion Criteria:\n\n1. Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening). Symptoms of mild mood dysphoria or anxiety are allowed as long as these symptoms are not the primary focus of treatment. A screening subject with mild substance abuse disorder within the 12 months before screening must be discussed and agreed upon with the medical monitor before they can be allowed into the study.\n2. Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.\n3. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.\n4. Subjects with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.\n5. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.\n6. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.\n7. Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).\n8. Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening.\n9. Subjects cannot currently (within 5 half-lives or 1 week, whichever is longer, before baseline \\[Day -1\\]) be receiving oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (eg, lamotrigine, Depakote); tricyclic antidepressants (eg, imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam, chloral hydrate).\n10. Pregnant, lactating, or less than 3 months postpartum.\n11. If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements.\n12. Positive test for coronavirus (COVID-19) within 2 weeks before screening and at screening.\n13. Subjects with extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.\n14. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening.\n15. Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) or required clozapine within the last 12 months.\n16. Subjects with prior exposure to KarXT.\n17. Subjects who experienced any adverse effects due to xanomeline or trospium.\n18. Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months before screening.\n19. Risk of violent or destructive behavior.\n20. Current involuntary hospitalization or incarceration."}, 'identificationModule': {'nctId': 'NCT04659161', 'briefTitle': 'A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-2)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Karuna Therapeutics'}, 'officialTitle': 'A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia', 'orgStudyIdInfo': {'id': 'KAR-007'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'KarXT', 'interventionNames': ['Drug: Xanomeline and Trospium Chloride Capsules']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Xanomeline and Trospium Chloride Capsules', 'type': 'DRUG', 'otherNames': ['KarXT'], 'description': 'Oral xanomeline 50 mg/trospium chloride 20 mg BID (twice a day) for the first 2 days (Days 1 and 2) followed by xanomeline 100 mg/trospium chloride 20 mg BID for the remainder of Week 1 (Days 3 to 7). At Visit 5 (Day 8), dosing was to be titrated upwards to xanomeline 125 mg/trospium chloride 30 mg BID unless the subject was continuing to experience adverse events (AEs) from the previous dose of KarXT 100/20 BID. All subjects who were increased to KarXT 125/30 BID, depending on clinical response and tolerability, had the option to return to KarXT 100/20 BID for the remainder of the treatment period.', 'armGroupLabels': ['KarXT']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['PBO'], 'description': 'Placebo Capsules twice a day (BID)', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '72211', 'city': 'Little Rock', 'state': 'Arkansas', 'country': 'United States', 'facility': 'Woodland International Research Group, LLC', 'geoPoint': {'lat': 34.74648, 'lon': -92.28959}}, {'zip': '90706', 'city': 'Bellflower', 'state': 'California', 'country': 'United States', 'facility': 'CITrials', 'geoPoint': {'lat': 33.88168, 'lon': -118.11701}}, {'zip': '90230', 'city': 'Culver City', 'state': 'California', 'country': 'United States', 'facility': 'ProScience Research Institute', 'geoPoint': {'lat': 34.02112, 'lon': -118.39647}}, {'zip': '91206', 'city': 'Glendale', 'state': 'California', 'country': 'United States', 'facility': 'California Clinical Trials Medical Group', 'geoPoint': {'lat': 34.14251, 'lon': -118.25508}}, {'zip': '91945', 'city': 'Lemon Grove', 'state': 'California', 'country': 'United States', 'facility': 'Synergy San Diego', 'geoPoint': {'lat': 32.74255, 'lon': -117.03142}}, {'zip': '90806', 'city': 'Long Beach', 'state': 'California', 'country': 'United States', 'facility': 'CNS Network', 'geoPoint': {'lat': 33.76696, 'lon': -118.18923}}, {'zip': '91763', 'city': 'Montclair', 'state': 'California', 'country': 'United States', 'facility': 'Catalina Research Institute, LLC', 'geoPoint': {'lat': 34.07751, 'lon': -117.68978}}, {'zip': '92868', 'city': 'Orange', 'state': 'California', 'country': 'United States', 'facility': 'NRC Research Institute', 'geoPoint': {'lat': 33.78779, 'lon': -117.85311}}, {'zip': '90660', 'city': 'Pico Rivera', 'state': 'California', 'country': 'United States', 'facility': 'California Neuropsychopharmacology Clinical Research Institute', 'geoPoint': {'lat': 33.98307, 'lon': -118.09673}}, {'zip': '92101', 'city': 'San Diego', 'state': 'California', 'country': 'United States', 'facility': 'California Neuropsychopharmacology Clinical Research Institute', 'geoPoint': {'lat': 32.71571, 'lon': -117.16472}}, {'zip': '91403', 'city': 'Sherman Oaks', 'state': 'California', 'country': 'United States', 'facility': 'Schuster Medical Research Institute', 'geoPoint': {'lat': 34.15112, 'lon': -118.44925}}, {'zip': '33016', 'city': 'Miami Lakes', 'state': 'Florida', 'country': 'United States', 'facility': 'Innovative Clinical Research, Inc.', 'geoPoint': {'lat': 25.90871, 'lon': -80.30866}}, {'zip': '33334', 'city': 'Oakland Park', 'state': 'Florida', 'country': 'United States', 'facility': 'Research Centers of America', 'geoPoint': {'lat': 26.17231, 'lon': -80.13199}}, {'zip': '30030', 'city': 'Decatur', 'state': 'Georgia', 'country': 'United States', 'facility': 'iResearch Atlanta, LLC', 'geoPoint': {'lat': 33.77483, 'lon': -84.29631}}, {'zip': '60640', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Uptown Research Institute', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '60712', 'city': 'Lincolnwood', 'state': 'Illinois', 'country': 'United States', 'facility': 'Pillar Clinical Research', 'geoPoint': {'lat': 42.00448, 'lon': -87.73006}}, {'zip': '63118', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Arch Clinical Trials', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '89102', 'city': 'Las Vegas', 'state': 'Nevada', 'country': 'United States', 'facility': 'Altea Research Institute', 'geoPoint': {'lat': 36.17497, 'lon': -115.13722}}, {'zip': '08053', 'city': 'Marlton', 'state': 'New Jersey', 'country': 'United States', 'facility': 'Hassman Research Institute', 'geoPoint': {'lat': 39.89122, 'lon': -74.92183}}, {'zip': '44720', 'city': 'North Canton', 'state': 'Ohio', 'country': 'United States', 'facility': 'Neuro-Behavioral Clinical Research', 'geoPoint': {'lat': 40.87589, 'lon': -81.40234}}, {'zip': '78754', 'city': 'Austin', 'state': 'Texas', 'country': 'United States', 'facility': 'Community Clinical Research', 'geoPoint': {'lat': 30.26715, 'lon': -97.74306}}, {'zip': '75080', 'city': 'Richardson', 'state': 'Texas', 'country': 'United States', 'facility': 'Pillar Clinical Research', 'geoPoint': {'lat': 32.94818, 'lon': -96.72972}}], 'overallOfficials': [{'name': 'Inder Kaul, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Karuna Therapeutics'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Karuna Therapeutics', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}