Clinical Trial Results:
A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of MIN-101 in Patients With Negative Symptoms of Schizophrenia, Followed by a 24-Week, Open-Label Extension.
Summary
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EudraCT number |
2014-004878-42 |
Trial protocol |
LV EE RO BG |
Global end of trial date |
02 Sep 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Sep 2018
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First version publication date |
27 Sep 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MIN-101C03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Minerva Neurosciences, Inc.
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Sponsor organisation address |
1601 Trapelo Road, Suite 286, Waltham, United States, 02451
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Public contact |
Joseph Reilly, Minerva Neurosciences, Inc., 1 6176007380, jreilly@minervaneurosciences.com
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Scientific contact |
Jay Saoud, Minerva Neurosciences, Inc., 1 6176007375, jsaoud@minervaneurosciences.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Dec 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Sep 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Sep 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to evaluate the efficacy of MIN-101 compared to placebo in improving the negative symptoms of schizophrenia as measured by the change from Baseline in the Positive and Negative Syndrome Scale (PANSS) negative subscale score of the pentagonal model over 12 weeks of treatment.
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Protection of trial subjects |
Prior to initiation of the study, the study protocol and associated documentation were reviewed and approved by an Independent Ethics Committee (IEC). This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practices (GCP) and applicable regulatory requirements. Subjects or their legally acceptable representatives provided their written consent to participate in the study after having been informed about the nature and purpose of the study, participation/termination conditions, and risks and benefits of treatment.
Personal data from subjects enrolled in this study was limited to those data necessary to investigate the efficacy, safety, quality, and utility of the investigational study agent(s) used in this study, and were collected and processed with adequate precautions to ensure confidentiality and compliance with applicable data privacy protection laws and regulations. Moreover, safety evaluations were performed during the study to ensure patient safety.
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Background therapy |
The most commonly taken concomitant medications (by >4% of subjects) were the benzodiazepines lorazepam (11 subjects, 4.5%) and phenazepam (10 subjects, 4.1%); both were used as rescue medications allowed by the study protocol. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Mar 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Romania: 56
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Country: Number of subjects enrolled |
Bulgaria: 37
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Country: Number of subjects enrolled |
Estonia: 1
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Country: Number of subjects enrolled |
Latvia: 11
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Country: Number of subjects enrolled |
Russian Federation: 36
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Country: Number of subjects enrolled |
Ukraine: 103
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Worldwide total number of subjects |
244
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EEA total number of subjects |
105
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
244
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Enrolled subjects were recruited for this study at 44 study centers in 6 countries (Bulgaria, Estonia, Latvia, Romania, Russia, and Ukraine). | ||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Subjects were screened for eligibility to participate in the study within 28 days before dosing. | ||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
342 [1] | ||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects completed |
244 | ||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Lost to follow-up: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Adverse event, non-fatal: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Physician decision: 2 | ||||||||||||||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Screening failure: 82 | ||||||||||||||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Subject moved out of area: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Consent withdrawn by subject: 6 | ||||||||||||||||||||||||||||||||||||||||||||||||
Reason: Number of subjects |
Other: 5 | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The number of subjects reported to have started the pre-assignment period include screened subjects (N=342); however, the worldwide number only includes the number of subjects enrolled (i.e., randomized) (N=244). |
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Period 1
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Period 1 title |
12-Week Double-Blind Study Phase
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | ||||||||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Study drug was packaged using a double-dummy, double-blind design.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Arm title
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MIN-101 32 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets identically matched in appearance (one MIN-101 32 mg tablet and one Placebo tablet). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Arm title
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MIN-101 64 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets (two MIN-101 32 mg tablets). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Period 2
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Period 2 title |
Whole Study Period
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | ||||||||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Whole study period includes 12 week randomized double-blind phase and 24-week open-label phase.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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MIN-101 32 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets identically matched in appearance (one MIN-101 32 mg tablet and one Placebo tablet). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets identically matched in appearance (one MIN-101 32 mg tablet and one Placebo tablet). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Arm title
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MIN-101 64 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets (two MIN-101 32 mg tablets). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets (two MIN-101 32 mg tablets). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Arm title
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Placebo to MIN-101 | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets identically matched in appearance (one MIN-101 32 mg tablet and one Placebo tablet). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Investigational medicinal product name |
MIN-101
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Investigational medicinal product code |
MIN-101
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose consisted of 2 tablets (two MIN-101 32 mg tablets). The study drug was to be administered in a single dose in the morning at approximately the same time each day, in fasting condition, and 2 hours before a light breakfast. Tablets were to be swallowed whole with water and not divided, crushed, chewed, or placed in water.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MIN-101 32 mg
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MIN-101 64 mg
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
- | ||
Reporting group title |
MIN-101 32 mg
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Reporting group description |
- | ||
Reporting group title |
MIN-101 64 mg
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Reporting group description |
- | ||
Reporting group title |
MIN-101 32 mg
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Reporting group description |
- | ||
Reporting group title |
MIN-101 64 mg
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Reporting group description |
- | ||
Reporting group title |
Placebo to MIN-101
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Reporting group description |
- |
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End point title |
Change from Baseline to Week 12 in PANSS Negative Symptoms Subscale (Pentagonal Structure Model) | ||||||||||||||||
End point description |
Change from Baseline to Week 12 in PANSS negative subscale score of the pentagonal structure model using mixed model repeated measures (MMRM) analysis, intent-to-treat population.
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End point type |
Primary
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End point timeframe |
Positive and Negative Syndrome Scale (PANSS) negative subscale score of the pentagonal structure model assessment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
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Statistical analysis title |
Change from Baseline to Week 12 in PANSS | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
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Comparison groups |
MIN-101 32 mg v MIN-101 64 mg v Placebo
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||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.024 [1] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [1] - MIN-101 32 mg vs Placebo: p ≤ 0.0240 MIN-101 64 mg vs Placebo p ≤ 0.0036 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in CGI-S | ||||||||||||||||
End point description |
Change from Baseline to Week 12 in Clinical Global Impression - Severity Scale Score (CGI-S), intent-to-treat (ITT) population. Least-squares mean are from an analysis of covariance (ANCOVA) of ranked data with treatment (Placebo, MIN-101 32 mg, MIN-101 64 mg) as a factor, and Baseline value as covariate.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Clinical Global Impression - Severity (CGI-S) assessment data were collected at Screening, Baseline, Weeks 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in CGI-S | ||||||||||||||||
Statistical analysis description |
Change from Baseline to Week 12 in Clinical Global Impression - Severity (CGI-S) Score using analysis of covariance (ANCOVA) of ranked data, with treatment (Placebo, MIN-101 32 mg, MIN-101 64 mg), as a factor and Baseline value as covariate.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.0982 [2] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [2] - MIN-101 32 mg vs Placebo: p ≤ 0.0982 MIN-101 64 mg vs Placebo: p ≤ 0.0234 |
|
|||||||||||||||||
End point title |
Clinical Global Impression - Global Improvement Scale Scores | ||||||||||||||||
End point description |
Change in Clinical Global Impression - Improvement Scale Score (CGI-I) with CGI-S as Baseline value, intent-to-treat (ITT) population. Least-squares mean are from an analysis of covariance (ANCOVA) of ranked data with treatment (Placebo, MIN-101 32 mg, MIN-101 64 mg) as a factor, and Baseline value as covariate.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Clinical Global Impression - Global Improvement assessment data were collected at Weeks 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Clinical Global Impression - Improvement Scores | ||||||||||||||||
Statistical analysis description |
Clinical Global Impression - Improvement Scores using analysis of covariance (ANCOVA) of ranked data, with treatment (Placebo, MIN-101 32 mg, MIN-101 64 mg), as a factor and Baseline value as covariate.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.2378 [3] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [3] - MIN-101 32 mg vs Placebo: p ≤ 0.2378 MIN-101 64 mg vs Placebo: p ≤ 0.0032 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in BACS Total Verbal Fluency Score | ||||||||||||||||
End point description |
Change from Baseline to Week 12 BACS using mixed model repeated measures (MMRM) analysis, intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Brief Assessment of Cognition in Schizophrenia (BACS) assessment data were collected at Baseline, Week 4, and Week 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in BACS Total | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
240
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.292 [4] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [4] - MIN-101 32 mg vs Placebo: p ≤ 0.292 MIN-101 64 mg vs Placebo: p ≤ 0.5446 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PANSS Total Score | ||||||||||||||||
End point description |
Change from Baseline to Week 12 in PANSS total score analysis using model from mixed-model repeated measures (MMRM) analysis, ITT population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) total score assessment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS Total | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.0819 [5] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [5] - MIN-101 32 mg vs Placebo: p ≤ 0.0819 MIN-101 64 mg vs Placebo: p ≤ 0.0031 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PANSS General Psychopathology Subscore | ||||||||||||||||
End point description |
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) General Psychopathology Scale Total Score of the 3 factors analysis using mixed model repeated measures (MMRM), intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) General Psychopathology Scale Total Score assessment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS GP Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.2359 [6] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [6] - MIN-101 32 mg vs Placebo: p ≤ 0.2359 MIN-101 64 mg vs Placebo: p ≤ 0.0034 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PANSS Negative Scale Total Score | ||||||||||||||||
End point description |
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Scale Total Score of the 3 factor analysis using mixed model repeated measures (MMRM), intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) Negative Scale Total Score assessment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS NS Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.0064 [7] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [7] - MIN-101 32 mg vs Placebo: p ≤ 0.0064 MIN-101 64 mg vs Placebo: p ≤ 0.0004 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PANSS Positive Scale Total Score | ||||||||||||||||
End point description |
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Scale Total Score of the 3 factors analysis using mixed model repeated measures (MMRM), intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) Positive Scale Total Score assessment data were collected at Screening, Baseline, Weeks 2, 4, 8 and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS PS Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.4018 [8] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [8] - MIN-101 32 mg vs Placebo: p ≤ 0.4018 MIN-101 64 mg vs Placebo: p ≤ 0.3067 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PANSS Positive Factor | ||||||||||||||||
End point description |
Change from Baseline in PANSS Positive Factor of the pentagonal model using mixed model repeated measures (MMRM) analysis, intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) Positive Factor assessment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS PF Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
MIN-101 32 mg v MIN-101 64 mg v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.5045 [9] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [9] - MIN-101 32 mg vs Placebo: p ≤ 0.5045 MIN-101 64 mg vs Placebo: p ≤ 0.2146 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PANSS Activation Factor | ||||||||||||||||
End point description |
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Activation Score of the pentagonal model using mixed model repeated measures (MMRM), intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) Activation Factor assesment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS AF Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.024 [10] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [10] - MIN-101 32 mg vs Placebo: p ≤ 0.0240 MIN-101 64 mg vs Placebo: p ≤ 0.0118 |
|
|||||||||||||||||
End point title |
Change from Baseline in PANSS Dysphoric Mood Factor | ||||||||||||||||
End point description |
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Dysphoric Mood Factor of the pentagonal model using mixed model repeated measures (MMRM), intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) Dysphoric Mood Factor assessment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS DM Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.5644 [11] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [11] - MIN-101 32 mg vs Placebo: p ≤ 0.5644 MIN-101 64 mg vs Placebo: p ≤ 0.0266 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PANSS Autistic Preoccupation Factor | ||||||||||||||||
End point description |
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Autistic Preoccupation Factor of the pentagonal model using mixed model repeated measures (MMRM), intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Positive and Negative Syndrome Scale (PANSS) Autistic Preoccupation Factor assessment data were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PANSS AP Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.67 [12] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [12] - MIN-101 32 mg vs Placebo: p ≤ 0.6700 MIN-101 64 mg vs Placebo: p ≤ 0.2408 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in BNSS Total Score | ||||||||||||||||
End point description |
Change from Baseline in Brief Negative Symptom Scale (BNSS) Total Score using mixed model repeated measures (MMRM) analysis, intent-to-treat population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Brief Negative Symptom Scale (BNSS) Total Score assessment data were collected at Baseline, Weeks 2, 4, 8, and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in BNSS Total | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.0869 [13] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [13] - MIN-101 32 mg vs Placebo: p ≤ 0.0869 MIN-101 64 mg vs Placebo: p ≤ 0.0040 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in PSP Total Score | ||||||||||||||||
End point description |
Change from Baseline in Personal and Social Performance (PSP) Total Score using mixed model repeated measures (MMRM), intent-to-treat population.
|
||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Personal and Social Performance (PSP) Total Score assessment data were collected at Baseline, and Weeks 4 and 12.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Change from Baseline to Week 12 in PSP Total Score | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
|
||||||||||||||||
Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
|
||||||||||||||||
Number of subjects included in analysis |
234
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
> 0.201 [14] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [14] - MIN-101 32 mg vs Placebo: p ≤ 0.2010 MIN-101 64 mg vs Placebo: p ≤ 0.0016 |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in Sheehan-STS Total Score | ||||||||||||||||
End point description |
The SSTS was adapted from the Suicidality Module of the MINI Structured Diagnostic Interview for DMS-IV. SSTS is an 8-item scale that can be administered by the clinician or the subject through self-report. Each item was scored on a 5-point Likert scale (0=not at all, 1=a little, 2=moderately, 3=very, and 4=extremely). Data from SSTS was analyzed as individual item scores, suicidal ideation subscale score (sum of scores from items 2, 3, and 4, plus score from item 5 if ≤1), suicidal behavior subscale score (sum of scores from items 6, 7a, and 8, plus score from item 5 if >1), and total score. On the basis of data collected using SSTS, potential suicide-related events were categorized by the investigator.
|
||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Sheehan Suicidality Tracking Scale (SSTS) scores were collected at Screening, Baseline, Day 2, and Weeks 2, 4, 8, 12, 12 ± 1-2 days, 14, 18, 24, 30, 36, and 37. SSTS scores are presented here for Week 12.
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in AIMS Score - Upper Extremities | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
|
||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in AIMS Score - Lower Extremities | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
|
||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in AIMS Score - Muscles of Facial Expression | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
|
||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in AIMS Score - Lips and Perioral Area | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
|
||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline to Week 12 in AIMS Score - Jaw | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
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End point type |
Other pre-specified
|
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End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
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No statistical analyses for this end point |
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End point title |
Change from Baseline to Week 12 in AIMS Score - Tongue | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
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End point type |
Other pre-specified
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End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
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No statistical analyses for this end point |
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End point title |
Change from Baseline to Week 12 in AIMS Score - Severity of Abnormal Movements | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
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End point type |
Other pre-specified
|
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End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
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No statistical analyses for this end point |
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End point title |
Change from Baseline to Week 12 in AIMS Score - Incapacitation due to Abnormal Movements | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
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End point type |
Other pre-specified
|
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End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
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No statistical analyses for this end point |
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End point title |
Change from Baseline to Week 12 in AIMS Score - Patient Awareness of Abnormal Movements | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
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End point type |
Other pre-specified
|
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End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
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No statistical analyses for this end point |
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End point title |
Change from Baseline to Week 12 in AIMS Score - Neck, Shoulders, Hips | ||||||||||||||||
End point description |
The AIMS was used as a safety assessment in this study to detect involuntary movements as potential adverse effects. Items were scored on a 5-point scale (0=none, 1=minimal, may be extreme normal, 2=mild, 3=moderate, 4=severe).
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End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Abnormal Involuntary Movement Scale (AIMS) scores were collected at Screening, Baseline, and Weeks 4, 8, 12, 18, 24, 30, 36, and 37. AIMS scores are presented here for Week 12.
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No statistical analyses for this end point |
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End point title |
Change from Baseline to Week 12 in CDSS Total Score | ||||||||||||||||
End point description |
Change from Baseline to Week 12 in Calgary Depression Scale for Schizophrenia (CDSS) scores, intent-to-treat population. Least-squares mean are from a mixed model repeated measures (MMRM) with treatment (Placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subjects nested in treatment as a random effect with Baseline value as covariates. An unstructured covariance matrix was used.
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End point type |
Other pre-specified
|
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End point timeframe |
Calgary Depression Scale for Schizophrenia scores for exploratory endpoint were collected at Screening, Baseline, Weeks 2, 4, 8, and 12.
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Statistical analysis title |
Change from Baseline to Week 12 in CDSS Total | ||||||||||||||||
Statistical analysis description |
MMRM with treatment (placebo, MIN-101 32 mg, MIN-101 64 mg), visit, pooled study center, and treatment-by-visit interaction terms as fixed effects, subject nested in treatment as a random effect with Baseline value as covariate. An unstructured covariance matrix was used.
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Comparison groups |
Placebo v MIN-101 32 mg v MIN-101 64 mg
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Number of subjects included in analysis |
234
|
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Analysis specification |
Pre-specified
|
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Analysis type |
superiority | ||||||||||||||||
P-value |
≤ 0.1756 [15] | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Confidence interval |
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Notes [15] - MIN-101 32 mg vs Placebo: p ≤ 0.1756 MIN-101 64 mg vs Placebo p ≤ 0.0091 |
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Adverse events information
|
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected from time of signed informed consent until completion of last study-related procedure.
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Adverse event reporting additional description |
Adverse events (AEs) were classified as treatment-emergent AEs (TEAEs) if the AEs were not present before the first dose or were present before first dose by increased in severity on or after first dose.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Placebo - Whole Study Period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MIN-101 32 mg - Whole Study Period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MIN-101 64 mg Whole Study Period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 3.5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |