Ignite Creation Date:
2025-12-25 @ 2:28 AM
Ignite Modification Date:
2026-03-09 @ 3:29 AM
Study NCT ID:
NCT02790034
Status:
TERMINATED
Last Update Posted:
2021-12-21
First Post:
2016-05-24
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015518', 'term': 'Rett Syndrome'}], 'ancestors': [{'id': 'D038901', 'term': 'X-Linked Intellectual Disability'}, {'id': 'D008607', 'term': 'Intellectual Disability'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D040181', 'term': 'Genetic Diseases, X-Linked'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C443959', 'term': 'sarizotan'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'regulatoryaffairs@newron.com', 'phone': '+41 793741364', 'title': 'Ravi Anand MD, Chief Medical Officer', 'organization': 'Newron Pharmaceuticals S.p.A.'}, 'certainAgreement': {'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'No efficacy evaluation was performed for the open label extension, as the study was terminated prematurely by the Sponsor based on lack of demonstrated efficacy in the double-blind period.'}}, 'adverseEventsModule': {'timeFrame': 'AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks.', 'description': 'Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39).\n\nClassification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP', 'eventGroups': [{'id': 'EG000', 'title': 'Sarizotan Low Dose', 'description': '2 mg or 5 mg bid based on age and weight criteria for 24 wks DB\n\n2 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n5 mg bid (≥13 years of age and weighing ≥25 kg)\n\nAssessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.', 'otherNumAtRisk': 33, 'deathsNumAtRisk': 33, 'otherNumAffected': 25, 'seriousNumAtRisk': 33, 'deathsNumAffected': 0, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Sarizotan High Dose', 'description': '5 mg or 10 mg bid based on age and weight criteria for 24 wks DB\n\n5 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n10 mg bid (≥13 years of age and weighing ≥25 kg)\n\nAssessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.', 'otherNumAtRisk': 56, 'deathsNumAtRisk': 56, 'otherNumAffected': 46, 'seriousNumAtRisk': 56, 'deathsNumAffected': 0, 'seriousNumAffected': 10}, {'id': 'EG002', 'title': 'Placebo', 'description': 'Placebo bid respectively\n\nPlacebo: placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.', 'otherNumAtRisk': 39, 'deathsNumAtRisk': 39, 'otherNumAffected': 30, 'seriousNumAtRisk': 39, 'deathsNumAffected': 0, 'seriousNumAffected': 5}], 'otherEvents': [{'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Seizure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 8, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 15, 'numAffected': 15}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Psychomotor hyperactivity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Dystonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Sleep Disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Urinary Tract Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}], 'seriousEvents': [{'term': 'Seizure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Gingival Hypertrophy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Lower respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Gingivitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Medication error', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Electrocardiogram QT prolonged', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Acute respiratory Failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Asthma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Change in seizure presentation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Generalised tonic-clonic seizure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Hyponatraemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Hypophagia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Lower respiratory tract infection bacterial', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Accidental Overdose', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}, {'term': 'Femur Fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 22.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Reduction in Respiratory Abnormality in Patients With Rett Syndrome', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}, {'value': '56', 'groupId': 'OG001'}, {'value': '40', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Sarizotan Low Dose', 'description': '2 mg or 5 mg bid based on age and weight criteria for 24 wks DB\n\n2 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n5 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'OG001', 'title': 'Sarizotan High Dose', 'description': '5 mg or 10 mg bid based on age and weight criteria for 24 wks DB\n\n5 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n10 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Placebo BID'}], 'classes': [{'categories': [{'measurements': [{'value': '1.54', 'spread': '10.1228', 'groupId': 'OG000'}, {'value': '13.211', 'spread': '7.5075', 'groupId': 'OG001'}, {'value': '18.503', 'spread': '8.441', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.6411', 'groupIds': ['OG001', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-5.292', 'ciLowerLimit': '-27.741', 'ciUpperLimit': '17.157', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '11.3184', 'groupDescription': 'Primary inferential comparison between treatment groups used a restricted maximum likelihood (REML)-based, mixed-effects repeated measures model approach (MMRM) with 95% CI for the difference between treatment groups for % change from baseline in the number of apnea episodes. Model included % change from baseline as response, the fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, and the continuous terms age and baseline value as covariate.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.2011', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-16.966', 'ciLowerLimit': '-43.119', 'ciUpperLimit': '9.186', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '13.1869', 'groupDescription': 'Primary inferential comparison between treatment groups used a restricted maximum likelihood (REML)-based, mixed-effects repeated measures model approach (MMRM) with 95% CI for the difference between treatment groups for % change from baseline in the number of apnea episodes. Model included % change from baseline as response, the fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, and the continuous terms age and baseline value as covariate.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline up to week 24', 'description': 'Measured as the percent change in the number of apnea episodes per hour during awake time, calculated using an ambulatory data acquisition system (BioRadioTM) as part of home monitoring procedure. BioRadioTM record specific respiratory and cardiac parameters.', 'unitOfMeasure': '% of change in mean counts per hr', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'The ITT population included all patients who were randomized to treatment. This population was used for all efficacy analysis.'}, {'type': 'SECONDARY', 'title': 'Efficacy of Sarizotan Assessed by the Caregiver-rated Impression of Change', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}, {'value': '56', 'groupId': 'OG001'}, {'value': '40', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Sarizotan Low Dose', 'description': '2 mg or 5 mg bid based on age and weight criteria for 24 wks DB\n\n2 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n5 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'OG001', 'title': 'Sarizotan High Dose', 'description': '5 mg or 10 mg bid based on age and weight criteria for 24 wks DB\n\n5 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n10 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'OG002', 'title': 'Placebo', 'description': 'Placebo BID'}], 'classes': [{'categories': [{'measurements': [{'value': '3.6', 'spread': '0.67', 'groupId': 'OG000'}, {'value': '3.5', 'spread': '1.12', 'groupId': 'OG001'}, {'value': '3.4', 'spread': '0.79', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': '24 weeks', 'description': "Caregiver-rated Impression of Change (CIC): 7-point scale requiring the caregiver to rate how much the patient's illness has improved or worsened relative to the baseline state.\n\n7-point Likert-type scale for which ratings range from 1 = very much improved to 7 = very much worse, with 4 = no change. This caregiver-rated measure considered activities, behavior, mood and functioning. This rating was performed in consultation with the study Investigator but was based largely on the caregivers' evaluation during the reporting period. The single rating of the CIC was to be based on changes in the following domains: • Activities (watching TV, interest in conversations around her, cooperation during toileting, dressing/bathing, etc.), • Communication (verbal or by eye movements, hand movements, or head movements), • Behavior (agitation, refusal to feed, scratching, social avoidance), • Participation in family/outdoor/social events)", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The ITT population included all patients who were randomized to treatment. This population was used for all efficacy analysis.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Sarizotan Low Dose', 'description': '2 mg or 5 mg bid based on age and weight criteria for 24 wks DB\n\n2 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n5 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'FG001', 'title': 'Sarizotan High Dose', 'description': '5 mg or 10 mg bid based on age and weight criteria for 24 wks DB\n\n5 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n10 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'FG002', 'title': 'Placebo', 'description': 'Placebo bid for 24 wks DB'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '33'}, {'groupId': 'FG001', 'numSubjects': '56'}, {'groupId': 'FG002', 'numSubjects': '40'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '27'}, {'groupId': 'FG001', 'numSubjects': '46'}, {'groupId': 'FG002', 'numSubjects': '36'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '10'}, {'groupId': 'FG002', 'numSubjects': '4'}]}]}], 'recruitmentDetails': 'The study was conducted at 14 sites in 5 countries. Enrollment occurred from 26-Oct-2016 through February 2019 . An analysis was planned when the primary efficacy data at Week 24 were available for all patients (06 August 2019 - last patient last visit for double-blind part of the study). Patients without safety and tolerability issues continued in the open label with sarizotan for an additional 24 weeks and then another 48 weeks if no safety issues were present.', 'preAssignmentDetails': 'A total of 198 patients were screened, of which 69 (34.8%) patients were screen failures.\n\nA total of 129 patients were randomized in the study. A total of 128 patients were exposed to at least one dose of IMP, with placebo ITT group (40) vs safety pop (39).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'BG000'}, {'value': '56', 'groupId': 'BG001'}, {'value': '40', 'groupId': 'BG002'}, {'value': '129', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Sarizotan Low Dose', 'description': '2 mg or 5 mg bid based on age and weight criteria for 24 wks DB\n\n2 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n5 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'BG001', 'title': 'Sarizotan High Dose', 'description': '5 mg or 10 mg bid based on age and weight criteria for 24 wks DB\n\n5 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg\n\n10 mg bid (≥13 years of age and weighing ≥25 kg)'}, {'id': 'BG002', 'title': 'Placebo', 'description': 'Placebo BID'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '35', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}, {'value': '85', 'groupId': 'BG003'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}, {'value': '44', 'groupId': 'BG003'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '13.23', 'spread': '7.195', 'groupId': 'BG000'}, {'value': '15.55', 'spread': '9.362', 'groupId': 'BG001'}, {'value': '14.13', 'spread': '9.155', 'groupId': 'BG002'}, {'value': '14.51', 'spread': '8.780', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '33', 'groupId': 'BG000'}, {'value': '56', 'groupId': 'BG001'}, {'value': '40', 'groupId': 'BG002'}, {'value': '129', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}, {'value': '13', 'groupId': 'BG003'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '29', 'groupId': 'BG000'}, {'value': '51', 'groupId': 'BG001'}, {'value': '36', 'groupId': 'BG002'}, {'value': '116', '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': [{'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': '8', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}, {'value': '37', 'groupId': 'BG003'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '5', 'groupId': 'BG003'}]}, {'title': 'White', 'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}, {'value': '82', 'groupId': 'BG003'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}, {'value': '41', 'groupId': 'BG003'}]}]}, {'title': 'Italy', 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}, {'value': '30', 'groupId': 'BG003'}]}]}, {'title': 'United Kingdom', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}, {'value': '21', 'groupId': 'BG003'}]}]}, {'title': 'Australia', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '3', 'groupId': 'BG003'}]}]}, {'title': 'India', 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}, {'value': '34', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Duration of Rett syndrome', 'classes': [{'categories': [{'measurements': [{'value': '87.90', 'spread': '72.536', 'groupId': 'BG000'}, {'value': '97.18', 'spread': '72.922', 'groupId': 'BG001'}, {'value': '73.94', 'spread': '65.800', 'groupId': 'BG002'}, {'value': '87.94', 'spread': '70.696', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'months', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-03-17', 'size': 2877120, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2021-10-08T16:09', 'hasProtocol': True}, {'date': '2020-03-30', 'size': 1289014, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2021-10-08T16:10', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 129}}, 'statusModule': {'whyStopped': 'The study did not demonstrate evidence of efficacy on the primary or secondary efficacy variables', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2016-10-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-11', 'completionDateStruct': {'date': '2020-05-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-11-22', 'studyFirstSubmitDate': '2016-05-24', 'resultsFirstSubmitDate': '2021-10-12', 'studyFirstSubmitQcDate': '2016-05-30', 'lastUpdatePostDateStruct': {'date': '2021-12-21', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-11-22', 'studyFirstPostDateStruct': {'date': '2016-06-03', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-12-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-08-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Reduction in Respiratory Abnormality in Patients With Rett Syndrome', 'timeFrame': 'Baseline up to week 24', 'description': 'Measured as the percent change in the number of apnea episodes per hour during awake time, calculated using an ambulatory data acquisition system (BioRadioTM) as part of home monitoring procedure. BioRadioTM record specific respiratory and cardiac parameters.'}], 'secondaryOutcomes': [{'measure': 'Efficacy of Sarizotan Assessed by the Caregiver-rated Impression of Change', 'timeFrame': '24 weeks', 'description': "Caregiver-rated Impression of Change (CIC): 7-point scale requiring the caregiver to rate how much the patient's illness has improved or worsened relative to the baseline state.\n\n7-point Likert-type scale for which ratings range from 1 = very much improved to 7 = very much worse, with 4 = no change. This caregiver-rated measure considered activities, behavior, mood and functioning. This rating was performed in consultation with the study Investigator but was based largely on the caregivers' evaluation during the reporting period. The single rating of the CIC was to be based on changes in the following domains: • Activities (watching TV, interest in conversations around her, cooperation during toileting, dressing/bathing, etc.), • Communication (verbal or by eye movements, hand movements, or head movements), • Behavior (agitation, refusal to feed, scratching, social avoidance), • Participation in family/outdoor/social events)"}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Rett Syndrome']}, 'referencesModule': {'references': [{'pmid': '20921395', 'type': 'BACKGROUND', 'citation': 'Abdala AP, Dutschmann M, Bissonnette JM, Paton JF. Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18208-13. doi: 10.1073/pnas.1012104107. Epub 2010 Oct 4.'}, {'pmid': '24910619', 'type': 'BACKGROUND', 'citation': 'Abdala AP, Bissonnette JM, Newman-Tancredi A. Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists. Front Physiol. 2014 May 30;5:205. doi: 10.3389/fphys.2014.00205. eCollection 2014.'}, {'pmid': '24351104', 'type': 'BACKGROUND', 'citation': 'Abdala AP, Lioy DT, Garg SK, Knopp SJ, Paton JF, Bissonnette JM. Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in three mouse models of Rett syndrome. Am J Respir Cell Mol Biol. 2014 Jun;50(6):1031-9. doi: 10.1165/rcmb.2013-0372OC.'}, {'pmid': '8265274', 'type': 'BACKGROUND', 'citation': 'Adams JA, Zabaleta IA, Stroh D, Sackner MA. Measurement of breath amplitudes: comparison of three noninvasive respiratory monitors to integrated pneumotachograph. Pediatr Pulmonol. 1993 Oct;16(4):254-8. doi: 10.1002/ppul.1950160408.'}, {'pmid': '9072988', 'type': 'BACKGROUND', 'citation': 'Bloch KE, Li Y, Sackner MA, Russi EW. Breathing pattern during sleep disruptive snoring. Eur Respir J. 1997 Mar;10(3):576-86.'}, {'pmid': '3625404', 'type': 'BACKGROUND', 'citation': 'Brouillette RT, Morrow AS, Weese-Mayer DE, Hunt CE. Comparison of respiratory inductive plethysmography and thoracic impedance for apnea monitoring. J Pediatr. 1987 Sep;111(3):377-83. doi: 10.1016/s0022-3476(87)80457-2.'}, {'pmid': '16263320', 'type': 'BACKGROUND', 'citation': 'Byard RW. Forensic issues and possible mechanisms of sudden death in Rett syndrome. J Clin Forensic Med. 2006 Feb;13(2):96-9. doi: 10.1016/j.jcfm.2005.08.013. Epub 2005 Nov 2.'}, {'pmid': '1395758', 'type': 'BACKGROUND', 'citation': 'Cantineau JP, Escourrou P, Sartene R, Gaultier C, Goldman M. Accuracy of respiratory inductive plethysmography during wakefulness and sleep in patients with obstructive sleep apnea. Chest. 1992 Oct;102(4):1145-51. doi: 10.1378/chest.102.4.1145.'}, {'pmid': '16162719', 'type': 'BACKGROUND', 'citation': 'Clarenbach CF, Senn O, Brack T, Kohler M, Bloch KE. Monitoring of ventilation during exercise by a portable respiratory inductive plethysmograph. Chest. 2005 Sep;128(3):1282-90. doi: 10.1378/chest.128.3.1282.'}, {'pmid': '18198809', 'type': 'BACKGROUND', 'citation': 'Collop NA, Anderson WM, Boehlecke B, Claman D, Goldberg R, Gottlieb DJ, Hudgel D, Sateia M, Schwab R; Portable Monitoring Task Force of the American Academy of Sleep Medicine. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2007 Dec 15;3(7):737-47.'}, {'type': 'BACKGROUND', 'citation': 'Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, May 28, 2009 (v4.03 June 14, 2010), U.S. Department of Health and Human Services.'}, {'pmid': '2388636', 'type': 'BACKGROUND', 'citation': 'FitzGerald PM, Jankovic J, Percy AK. Rett syndrome and associated movement disorders. Mov Disord. 1990;5(3):195-202. doi: 10.1002/mds.870050303.'}, {'type': 'BACKGROUND', 'citation': 'Guy W (Ed). Clinical Global Impressions. In ECDEU Assessment Manual for Psychopharmacology, revised, U.S. Department of Health, Education and Welfare Pub. No. (ADM) 76-338. Rockville, MD: NIMH, 1976, 217-222.'}, {'pmid': '7792119', 'type': 'BACKGROUND', 'citation': 'Hammer J, Newth CJ, Deakers TW. Validation of the phase angle technique as an objective measure of upper airway obstruction. Pediatr Pulmonol. 1995 Mar;19(3):167-73. doi: 10.1002/ppul.1950190305.'}, {'pmid': '9487980', 'type': 'BACKGROUND', 'citation': "Julu PO, Kerr AM, Hansen S, Apartopoulos F, Jamal GA. Immaturity of medullary cardiorespiratory neurones leading to inappropriate autonomic reactions as a likely cause of sudden death in Rett's syndrome. Arch Dis Child. 1997 Nov;77(5):464-5. doi: 10.1136/adc.77.5.463c. No abstract available."}, {'pmid': '11420195', 'type': 'BACKGROUND', 'citation': 'Julu PO, Kerr AM, Apartopoulos F, Al-Rawas S, Engerstrom IW, Engerstrom L, Jamal GA, Hansen S. Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder. Arch Dis Child. 2001 Jul;85(1):29-37. doi: 10.1136/adc.85.1.29.'}, {'pmid': '18555901', 'type': 'BACKGROUND', 'citation': "Julu PO, Engerstrom IW, Hansen S, Apartopoulos F, Engerstrom B, Pini G, Delamont RS, Smeets EE. Cardiorespiratory challenges in Rett's syndrome. Lancet. 2008 Jun 14;371(9629):1981-3. doi: 10.1016/S0140-6736(08)60849-1. No abstract available."}, {'pmid': '19394452', 'type': 'BACKGROUND', 'citation': 'Katz DM, Dutschmann M, Ramirez JM, Hilaire G. Breathing disorders in Rett syndrome: progressive neurochemical dysfunction in the respiratory network after birth. Respir Physiol Neurobiol. 2009 Aug 31;168(1-2):101-8. doi: 10.1016/j.resp.2009.04.017. Epub 2009 Apr 24.'}, {'pmid': '9452925', 'type': 'BACKGROUND', 'citation': 'Kerr AM, Armstrong DD, Prescott RJ, Doyle D, Kearney DL. Rett syndrome: analysis of deaths in the British survey. Eur Child Adolesc Psychiatry. 1997;6 Suppl 1:71-4.'}, {'pmid': '24623853', 'type': 'BACKGROUND', 'citation': "Khwaja OS, Ho E, Barnes KV, O'Leary HM, Pereira LM, Finkelstein Y, Nelson CA 3rd, Vogel-Farley V, DeGregorio G, Holm IA, Khatwa U, Kapur K, Alexander ME, Finnegan DM, Cantwell NG, Walco AC, Rappaport L, Gregas M, Fichorova RN, Shannon MW, Sur M, Kaufmann WE. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4596-601. doi: 10.1073/pnas.1311141111. Epub 2014 Mar 12."}, {'pmid': '4225383', 'type': 'BACKGROUND', 'citation': 'Konno K, Mead J. Measurement of the separate volume changes of rib cage and abdomen during breathing. J Appl Physiol. 1967 Mar;22(3):407-22. doi: 10.1152/jappl.1967.22.3.407. No abstract available.'}, {'type': 'BACKGROUND', 'citation': 'Landon C. Respiratory monitoring: Advantages of inductive plethysmography over impedance pneumograpy. VivoMetrics, VMLA-039-02, 2003.'}, {'pmid': '11152021', 'type': 'BACKGROUND', 'citation': 'Leino K, Nunes S, Valta P, Takala J. Validation of a new respiratory inductive plethysmograph. Acta Anaesthesiol Scand. 2001 Jan;45(1):104-11. doi: 10.1034/j.1399-6576.2001.450116.x.'}, {'pmid': '10334149', 'type': 'BACKGROUND', 'citation': 'Loube DI, Andrada T, Howard RS. Accuracy of respiratory inductive plethysmography for the diagnosis of upper airway resistance syndrome. Chest. 1999 May;115(5):1333-7. doi: 10.1378/chest.115.5.1333.'}, {'pmid': '18337588', 'type': 'BACKGROUND', 'citation': 'Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, Zoghbi H, Percy A, Glaze DG. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008 Apr 15;70(16):1313-21. doi: 10.1212/01.wnl.0000291011.54508.aa. Epub 2008 Mar 12.'}, {'pmid': '21154482', 'type': 'BACKGROUND', 'citation': 'Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010 Dec;68(6):944-50. doi: 10.1002/ana.22124.'}, {'pmid': '25895911', 'type': 'BACKGROUND', 'citation': 'Neul JL, Glaze DG, Percy AK, Feyma T, Beisang A, Dinh T, Suter B, Anagnostou E, Snape M, Horrigan J, Jones NE. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale. J Child Neurol. 2015 Nov;30(13):1743-8. doi: 10.1177/0883073815579707. Epub 2015 Apr 20.'}, {'pmid': '2917945', 'type': 'BACKGROUND', 'citation': 'Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky F, Krieger B. Calibration of respiratory inductive plethysmograph during natural breathing. J Appl Physiol (1985). 1989 Jan;66(1):410-20. doi: 10.1152/jappl.1989.66.1.410.'}, {'pmid': '22192257', 'type': 'BACKGROUND', 'citation': 'Weng SM, Bailey ME, Cobb SR. Rett syndrome: from bed to bench. Pediatr Neonatol. 2011 Dec;52(6):309-16. doi: 10.1016/j.pedneo.2011.08.002. Epub 2011 Nov 6.'}, {'pmid': '33862302', 'type': 'DERIVED', 'citation': 'Gualniera L, Singh J, Fiori F, Santosh P. Emotional Behavioural and Autonomic Dysregulation (EBAD) in Rett Syndrome - EDA and HRV monitoring using wearable sensor technology. J Psychiatr Res. 2021 Jun;138:186-193. doi: 10.1016/j.jpsychires.2021.03.052. Epub 2021 Apr 7.'}]}, 'descriptionModule': {'briefSummary': 'This study evaluates the safety, tolerability and efficacy of Sarizotan in reducing respiratory abnormalities in Rett Syndrome in an initial double blind 24 week period followed by an open label treatment phase of up to 168 weeks (the latter for patients with no safety and tolerability issues).', 'detailedDescription': 'This is a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and efficacy of multiple doses of sarizotan in patients with Rett syndrome with respiratory abnormalities. The study participants will be randomized to either sarizotan between 2 and 10 mg bid or placebo bid, based on age and weight criteria.\n\nAll patients who have completed the final evaluations at Week 24 (Day 168) and have no safety or tolerability issues that would preclude continuing on the study medication and have been compliant with the trial requirements will have the option of continuing open-label treatment with Sarizotan for up to 168 weeks.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '4 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Body weight ≥ 10 kg\n* Age ≥ 4 years\n* Diagnosis of Rett syndrome based on consensus clinical criteria and patients with MECP2 duplications will not be eligible.\n* Has at least 10 episodes of breathing dysrhythmia, defined by episodes ≥10 seconds of breath holding (apnea), per hour during cardiorespiratory monitoring\n* Ability to take study medication provided either as capsules or combined with food/drink.\n* Patient is cooperative, willing to complete all aspects of the study, and capable of doing so with assistance of a caregiver.\n\nExclusion Criteria:\n\n* Meets any of the diagnostic exclusion criteria for Rett syndrome, Typical (Neul et al, 2010);\n* Patient is participating in a clinical trial with another investigational drug\n* Hypersensitivity to sarizotan or other 5-HT1a agonists;\n* Current clinically significant (as determined by Investigator) cardiovascular, respiratory (e.g. severe asthma), gastrointestinal, renal, hepatic, hematologic or other medical disorders, in addition to those directly related to the patient's Rett syndrome;\n* QTcF interval on the ECG is greater than 450 msec.\n* Surgery planned during the study (except for insertion of gastrostomy tube);\n* Severe diabetes mellitus or fatty acid oxidation disorder.\n* Ophthalmologic history including any of the following conditions: albino patients, family history of hereditary retinal disease, retinitis pigmentosa, any active retinopathy or severe diabetic retinopathy.\n* Females who are pregnant, breastfeeding, or of childbearing potential and not using a hormonal contraceptive."}, 'identificationModule': {'nctId': 'NCT02790034', 'acronym': 'STARS', 'briefTitle': 'Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms', 'organization': {'class': 'INDUSTRY', 'fullName': 'Newron Pharmaceuticals SPA'}, 'officialTitle': 'A Randomised, Double-Blind, Placebo-Controlled 6-month Study to Evaluate the Efficacy, Safety, and Tolerability of Sarizotan in Patients With Rett Syndrome With Respiratory Symptoms', 'orgStudyIdInfo': {'id': 'Sarizotan/001/II/2015'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sarizotan low dose', 'description': '2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)', 'interventionNames': ['Drug: Sarizotan low dose']}, {'type': 'EXPERIMENTAL', 'label': 'Sarizotan high dose', 'description': '5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)', 'interventionNames': ['Drug: Sarizotan high dose']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo bid for 24 wks DB age 4 and above', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Sarizotan low dose', 'type': 'DRUG', 'description': '2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg; 5 mg bid (≥13 years of age and weighing ≥25 kg). Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.', 'armGroupLabels': ['Sarizotan low dose']}, {'name': 'Sarizotan high dose', 'type': 'DRUG', 'description': '5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to \\<13 years; ≥13 years of age and weighing \\<25 kg; 10 mg bid (≥13 years of age and weighing ≥25 kg) Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients', 'armGroupLabels': ['Sarizotan high dose']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35233', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'University of Alabama', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '92093', 'city': 'San Diego', 'state': 'California', 'country': 'United States', 'facility': 'University of California', 'geoPoint': {'lat': 32.71571, 'lon': -117.16472}}, {'zip': '60612', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Rush University Medical Center', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '55101', 'city': 'Saint Paul', 'state': 'Minnesota', 'country': 'United States', 'facility': "Gillette Children's Specialty Healthcare", 'geoPoint': {'lat': 44.94441, 'lon': -93.09327}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Baylor College of Medicine', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '6961', 'city': 'Murdoch', 'state': 'Western Australia', 'country': 'Australia', 'facility': 'South Metropolitan Health Service Fiona Stanley Hospital', 'geoPoint': {'lat': -32.06987, 'lon': 115.83757}}, {'zip': '682041', 'city': 'Kochi', 'state': 'Kerala', 'country': 'India', 'facility': 'Amrita Institute of Medical Sciences', 'geoPoint': {'lat': 9.93988, 'lon': 76.26022}}, {'zip': '600 026', 'city': 'Chennai', 'state': 'Tamil Nadu', 'country': 'India', 'facility': 'Vijaya Health Centre', 'geoPoint': {'lat': 13.08784, 'lon': 80.27847}}, {'zip': '400 016', 'city': 'Mumbai', 'country': 'India', 'facility': 'P.D. Hinduja National Hospital and Medical Research Centre', 'geoPoint': {'lat': 19.07283, 'lon': 72.88261}}, {'zip': '400 026', 'city': 'Mumbai', 'country': 'India', 'facility': 'Jaslok Hospital and Research centre', 'geoPoint': {'lat': 19.07283, 'lon': 72.88261}}, {'zip': '110 029', 'city': 'New Delhi', 'country': 'India', 'facility': 'All India Institute of Medical Sciences', 'geoPoint': {'lat': 28.62137, 'lon': 77.2148}}, {'zip': '53100', 'city': 'Siena', 'state': 'Tuscany', 'country': 'Italy', 'facility': 'A.O.U. Senese Policlinico Santa Maria alle Scotte', 'geoPoint': {'lat': 43.31822, 'lon': 11.33064}}, {'zip': '20142', 'city': 'Milan', 'country': 'Italy', 'facility': 'U.O. Neuropsichiatria Infantile', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}, {'zip': 'SE5 8AF', 'city': 'London', 'country': 'United Kingdom', 'facility': "King's College Hospital", 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Ravi Anand, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Newron Pharmaceuticals'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Newron Pharmaceuticals SPA', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}