Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo- and Active Comparator-controlled Trial of Flexible-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial.
Summary
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EudraCT number |
2012-003948-67 |
Trial protocol |
DE SK FR ES |
Global end of trial date |
10 Nov 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jan 2018
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First version publication date |
26 Jan 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 |
331-12-282
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND No.: 103, 958 | ||
Sponsors
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Sponsor organisation name |
Otsuka Pharmaceutical Development & Commercialization,
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Sponsor organisation address |
2440 Research Boulevard, Rockville, Maryland , United States, 20850
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Public contact |
Regulatory Project Manager, INC Research, +34 916307400, ricardo.sanz-gadea@incresearch.com
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Scientific contact |
Regulatory Project Manager, INC Research, +34 916307400, ricardo.sanz-gadea@incresearch.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 |
10 Nov 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Nov 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Nov 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 |
To compare the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy to an assigned openlabel antidepressant therapy (ADT) in the proposed subject population with major depressive disorder (MDD).
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Protection of trial subjects |
The study was conducted in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline, and the applicable local laws and regulatory requirements of the countries in which the trial was conducted, copies of the protocol, any amendments, and the informed consent form (ICF) were reviewed and approved by the governing institutional review board (IRB) or independent ethics committee (IEC) for
each investigational site or country, as appropriate, prior to trial start or prior to implementation of the protocol or protocol amendment, if any, at that site and/or country.. Written informed consent (translated in Canadian French, German, French, Russian, Polish, and Serbian) was obtained from all subjects (or their guardian or legal representative, as applicable according to local laws) and was documented prior to initiation of any procedures that were performed solely for the purpose of determining eligibility for this trial, including withdrawal from current medication(s).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Nov 2012
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Long term follow-up planned |
No
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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 |
United States: 239
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Country: Number of subjects enrolled |
Russian Federation: 165
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Country: Number of subjects enrolled |
Serbia: 6
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Country: Number of subjects enrolled |
Poland: 53
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Country: Number of subjects enrolled |
France: 6
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Country: Number of subjects enrolled |
Germany: 34
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Worldwide total number of subjects |
503
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EEA total number of subjects |
93
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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) |
501
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Trial was conducted at 75 trial sites in 7 countries (United States, Russia, Poland, France, Serbia, Germany & Canada). Of the screened 3001 subjects (with major depressive disorder), 2182 entered Phase A, 503 (non-responders) were randomized into Phase B (brexpiprazole/Seroquel/placebo +ADT) and 1394 entered Phase A+ (continued Phase A therapy) | ||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Screening period ranged from a minimum of 7 days to a maximum of 28 days and began when informed consent was signed. The purpose was to assess eligibility criteria at 1 or more visits (as necessary to complete screening assessments) and to washout (minimum of 24 hours) prohibited concomitant pharmacotherapy, if applicable. | ||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Phase B (overall period)
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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 | ||||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Investigational medicinal product (placebo, brexpiprazole, or Seroquel XR) other than ADT was double-blind at any given visit. Personnel at trial sites were blinded to details of randomization criteria & dosing schedule. Except in cases of emergency unblinding, subjects, investigational site personnel, sponsor employees, and all other trial personnel remained blinded to the identity of the treatment assignments until every
subject had completed trial treatment and the database had been locked
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Brexpiprazole + Antidepressant therapy (ADT) | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received orally brexpiprazole 1 mg tablet per day and assigned ADT at randomization, and then the dose was increased to 2 mg/day at Day 7 (± 2 days). Subjects remained at the target dose (2 mg/day) unless the investigator requested an increase to a higher dose. Change in the dose was done based on a clinical assessment of the benefit and the subject’s tolerance of the investigational medicinal product (IMP). The choice of ADT was determined by considering each subject's antidepressant treatment history. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Brexpiprazole
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Investigational medicinal product code |
OPC-34712
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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 |
Orally brexpiprazole 1 mg tablet per day at randomization, and then the dose was increased to 2 mg/day at Day 7 (± 2 days).
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Arm title
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Quetiapine (Seroquel) extended release (XR) + ADT | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Randomized subjects received orally quetiapine XR tablets at a dose of 50 mg/day and assigned ADT therapy on Day 1 and Day 2, and then the dose was increased to 150 mg/day on Day 3 through Day 14. Subjects remained at the target dose (150 mg/day) unless the investigator requested an increase to a higher dose. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Quetiapine XR tablet
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Investigational medicinal product code |
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Other name |
Seroquel XR
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Orally quetiapine 50 mg XR tablet per day on Day 1 and Day 2, and then the dose was increased to 150 mg/day on Day 3 through Day 14.
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Arm title
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Placebo + ADT | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Randomized subjects received orally brexpiprazole or quetiapine matching placebo tablets with the open-label ADT (Phase A) at the final dose reached during the prospective treatment phase. | ||||||||||||||||||||||||||||||||||||||||||||
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 |
Orally brexpiprazole or quetiapine matching placebo tablets with the open-label ADT final dose reached during the prospective treatment phase (Phase A).
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Baseline characteristics reporting groups
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Reporting group title |
Brexpiprazole + Antidepressant therapy (ADT)
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Reporting group description |
Subjects received orally brexpiprazole 1 mg tablet per day and assigned ADT at randomization, and then the dose was increased to 2 mg/day at Day 7 (± 2 days). Subjects remained at the target dose (2 mg/day) unless the investigator requested an increase to a higher dose. Change in the dose was done based on a clinical assessment of the benefit and the subject’s tolerance of the investigational medicinal product (IMP). The choice of ADT was determined by considering each subject's antidepressant treatment history. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Quetiapine (Seroquel) extended release (XR) + ADT
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Reporting group description |
Randomized subjects received orally quetiapine XR tablets at a dose of 50 mg/day and assigned ADT therapy on Day 1 and Day 2, and then the dose was increased to 150 mg/day on Day 3 through Day 14. Subjects remained at the target dose (150 mg/day) unless the investigator requested an increase to a higher dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + ADT
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Reporting group description |
Randomized subjects received orally brexpiprazole or quetiapine matching placebo tablets with the open-label ADT (Phase A) at the final dose reached during the prospective treatment phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Brexpiprazole + Antidepressant therapy (ADT)
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Reporting group description |
Subjects received orally brexpiprazole 1 mg tablet per day and assigned ADT at randomization, and then the dose was increased to 2 mg/day at Day 7 (± 2 days). Subjects remained at the target dose (2 mg/day) unless the investigator requested an increase to a higher dose. Change in the dose was done based on a clinical assessment of the benefit and the subject’s tolerance of the investigational medicinal product (IMP). The choice of ADT was determined by considering each subject's antidepressant treatment history. | ||
Reporting group title |
Quetiapine (Seroquel) extended release (XR) + ADT
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Reporting group description |
Randomized subjects received orally quetiapine XR tablets at a dose of 50 mg/day and assigned ADT therapy on Day 1 and Day 2, and then the dose was increased to 150 mg/day on Day 3 through Day 14. Subjects remained at the target dose (150 mg/day) unless the investigator requested an increase to a higher dose. | ||
Reporting group title |
Placebo + ADT
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Reporting group description |
Randomized subjects received orally brexpiprazole or quetiapine matching placebo tablets with the open-label ADT (Phase A) at the final dose reached during the prospective treatment phase. |
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End point title |
Mean Change From Randomization (End of Phase A) to End of Phase B in montgomery asberg depression rating scale (MADRS) Total Score - Efficacy Sample | ||||||||||||||||
End point description |
To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS was used to asses the subject’s level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts) each with 7 defined grades of severity. If a subject discontinued early, every effort was made to complete the “End of Week 18/ET” evaluations.
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End point type |
Primary
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End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ early termination (ET) Visit
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Statistical analysis title |
Bbrexpiprazole+ADT Vs Placebo+ADT | ||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
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Comparison groups |
Placebo + ADT v Brexpiprazole + Antidepressant therapy (ADT)
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Number of subjects included in analysis |
396
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0078 | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-1.48
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-2.56 | ||||||||||||||||
upper limit |
-0.39 | ||||||||||||||||
Statistical analysis title |
Seroquel XR+ADT Vs Placebo+ADT | ||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
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Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
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Number of subjects included in analysis |
304
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6642 | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-0.3
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-1.63 | ||||||||||||||||
upper limit |
1.04 |
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End point title |
Mean change from randomization (End of Phase A) to end of Phase B in Sheehan Disability Scale (SDS) score | ||||||||||||||||
End point description |
The SDS is a self-rated instrument used to measure the effect of the subject’s symptoms on work/school, social life, and family/home responsibilities. It was a visual analogue scale which used spatio-visual, numeric, and verbal descriptive anchors to assess disability across 3 domains and the symptom was marked along the line from 0 (not at all) to 10 (extreme). Scores of 5 and above was associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment.
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End point type |
Secondary
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End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ ET Visit
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Statistical analysis title |
Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
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Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
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Number of subjects included in analysis |
396
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.1334 | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
-0.23
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-0.52 | ||||||||||||||||
upper limit |
0.07 | ||||||||||||||||
Statistical analysis title |
Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
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Comparison groups |
Placebo + ADT v Quetiapine (Seroquel) extended release (XR) + ADT
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Number of subjects included in analysis |
304
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.0237 | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||
Point estimate |
0.42
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
0.06 | ||||||||||||||||
upper limit |
0.78 |
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End point title |
Mean Change From Randomization (End of Phase A) to Phase B by Trial Week in MADRS Total Score at Week 2 visit and Week 4 visit | ||||||||||||||||||||||||
End point description |
To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS was used to asses the subject’s level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts) each with 7 defined grades of severity. If a subject discontinued early, every effort was made to complete the “End of Week 18/ET” evaluations.
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End point type |
Secondary
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End point timeframe |
Treatment Phase: At Week 2 visit and Week 4 visit
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Statistical analysis title |
Week 2 visit: Brexpiprazole+ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
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Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
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Number of subjects included in analysis |
396
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0001 | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-1.53
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-2.29 | ||||||||||||||||||||||||
upper limit |
-0.76 | ||||||||||||||||||||||||
Statistical analysis title |
Week 2 visit: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
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Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
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Number of subjects included in analysis |
304
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0103 | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-1.22
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-2.15 | ||||||||||||||||||||||||
upper limit |
-0.29 | ||||||||||||||||||||||||
Statistical analysis title |
Week 4 visit: Brexpiprazole+ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
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Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
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Number of subjects included in analysis |
396
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0185 | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-1.17
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-2.15 | ||||||||||||||||||||||||
upper limit |
-0.2 | ||||||||||||||||||||||||
Statistical analysis title |
Week 4 visit: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.8949 | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||
Point estimate |
-0.08
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-1.27 | ||||||||||||||||||||||||
upper limit |
1.11 |
|
|||||||||||||||||||||||||||||
End point title |
Mean Change from End of Phase A to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) Scale | ||||||||||||||||||||||||||||
End point description |
The severity of illness for each subject was rated using the CGI-S. To perform this assessment, the rater or investigator answered the following question: “Considering your total clinical experience with this particular population, how mentally ill is the patient at
this time?” Response choices include: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ ET Visit
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Statistical analysis title |
Week 2: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.0369 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
-0.11
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.21 | ||||||||||||||||||||||||||||
upper limit |
-0.01 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 2: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.2468 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
-0.07
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.19 | ||||||||||||||||||||||||||||
upper limit |
0.05 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 4: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.0764 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
-0.11
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.23 | ||||||||||||||||||||||||||||
upper limit |
0.01 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 4: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.8258 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
0.02
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.13 | ||||||||||||||||||||||||||||
upper limit |
0.17 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 6: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.035 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
-0.15
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.29 | ||||||||||||||||||||||||||||
upper limit |
-0.01 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 6: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.5601 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
-0.05
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.22 | ||||||||||||||||||||||||||||
upper limit |
0.12 |
|
|||||||||||||||||||||||||||||
End point title |
Mean Clinical Global Impression Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A | ||||||||||||||||||||||||||||
End point description |
The improvement of each subject’s condition was rated for each subject using the CGI-I. The rater or investigator rated the subject’s total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the rater or investigator answered the following question: “Compared to his/her condition at baseline, how much has the patient changed?” Response choices include: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ ET Visit
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Statistical analysis title |
Week 2: Bbrexpiprazole+ADT Vs Placebo+ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.0156 | ||||||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||
Point estimate |
-0.18
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.32 | ||||||||||||||||||||||||||||
upper limit |
-0.03 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 2: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.2053 | ||||||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||
Point estimate |
-0.11
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.27 | ||||||||||||||||||||||||||||
upper limit |
0.06 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 4: Bbrexpiprazole+ADT Vs Placebo+ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.0222 | ||||||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||
Point estimate |
-0.17
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.31 | ||||||||||||||||||||||||||||
upper limit |
-0.02 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 4: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.9403 | ||||||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||
Point estimate |
-0.01
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.18 | ||||||||||||||||||||||||||||
upper limit |
0.17 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 6: Bbrexpiprazole+ADT Vs Placebo+ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.0146 | ||||||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||
Point estimate |
-0.19
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.35 | ||||||||||||||||||||||||||||
upper limit |
-0.04 | ||||||||||||||||||||||||||||
Statistical analysis title |
Week 6: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.7127 | ||||||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||
Point estimate |
-0.04
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.23 | ||||||||||||||||||||||||||||
upper limit |
0.15 |
|
|||||||||||||||||||||||||
End point title |
MADRS Response Rate (>= 50% reduction in total score) for every trial week visit during double-blind randomized Phase B treatment | ||||||||||||||||||||||||
End point description |
The rating was based on a clinical interview moving from broadly phrased questions about symptoms to more detailed ones which allowed a precise rating of severity. The rater decided whether the rating lies on predefined scale steps (0, 2, 4, 6) or between them (1, 3, 5).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ ET Visit
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Week 2: Bbrexpiprazole+ADT Vs Placebo+ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.8396 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.19
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.22 | ||||||||||||||||||||||||
upper limit |
6.31 | ||||||||||||||||||||||||
Statistical analysis title |
Week 2: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.2413 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Statistical analysis title |
Week 4: Bbrexpiprazole+ADT Vs Placebo+ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.4131 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ration of response rate | ||||||||||||||||||||||||
Point estimate |
1.57
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.53 | ||||||||||||||||||||||||
upper limit |
4.62 | ||||||||||||||||||||||||
Statistical analysis title |
Week 4: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.6976 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.32
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.33 | ||||||||||||||||||||||||
upper limit |
5.22 | ||||||||||||||||||||||||
Statistical analysis title |
Week 6: Bbrexpiprazole+ADT Vs Placebo+ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.2242 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.49
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.78 | ||||||||||||||||||||||||
upper limit |
2.84 | ||||||||||||||||||||||||
Statistical analysis title |
Week 6: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.5998 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.26
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.53 | ||||||||||||||||||||||||
upper limit |
2.98 |
|
|||||||||||||||||||||||||
End point title |
MADRS Remission Rate(<=10 and >=50% reduction in total score) for every trial week visit during double-blind randomized Phase B treatment | ||||||||||||||||||||||||
End point description |
The rating was based on a clinical interview moving from broadly phrased questions about symptoms to more detailed ones which allowed a precise rating of severity. The rater decided whether the rating lies on predefined scale steps (0, 2, 4, 6) or between them (1, 3, 5).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ ET Visit
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Week 2: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.8711 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.33
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.04 | ||||||||||||||||||||||||
upper limit |
43.6 | ||||||||||||||||||||||||
Statistical analysis title |
Week 2: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.4795 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Statistical analysis title |
Week 4: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.8117 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.2
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.26 | ||||||||||||||||||||||||
upper limit |
5.45 | ||||||||||||||||||||||||
Statistical analysis title |
Week 4: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.2169 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Statistical analysis title |
Week 6: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.3321 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.52
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.66 | ||||||||||||||||||||||||
upper limit |
3.49 | ||||||||||||||||||||||||
Statistical analysis title |
Week 6: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.3917 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
0.51
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.11 | ||||||||||||||||||||||||
upper limit |
2.46 |
|
|||||||||||||||||||||||||
End point title |
CGI-I Response rate for every trial week visit during double-blind randomized Phase B treatment | ||||||||||||||||||||||||
End point description |
The response was defined as a CGI-I score of 1 or 2 (very much improved or much improved).
The improvement of each subject’s condition was rated for each subject using the CGI-I. The rater or investigator rated the subject’s total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the rater or investigator answered the following question: “Compared to his/her condition at baseline, how much has the patient changed?” Response choices include: 1 = very much improved and 2 = much improved.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ ET Visit
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Week 2: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0072 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.62
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
1.13 | ||||||||||||||||||||||||
upper limit |
2.31 | ||||||||||||||||||||||||
Statistical analysis title |
Week 2: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.1501 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.39
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.9 | ||||||||||||||||||||||||
upper limit |
2.15 | ||||||||||||||||||||||||
Statistical analysis title |
Week 4: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0194 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.35
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
1.04 | ||||||||||||||||||||||||
upper limit |
1.74 | ||||||||||||||||||||||||
Statistical analysis title |
Week 4: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Placebo + ADT v Quetiapine (Seroquel) extended release (XR) + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.2934 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.19
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.87 | ||||||||||||||||||||||||
upper limit |
1.63 | ||||||||||||||||||||||||
Statistical analysis title |
Week 6: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0032 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.35
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
1.1 | ||||||||||||||||||||||||
upper limit |
1.66 | ||||||||||||||||||||||||
Statistical analysis title |
Week 6: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0898 | ||||||||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||||||||
Parameter type |
Ratio of response rate | ||||||||||||||||||||||||
Point estimate |
1.24
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.98 | ||||||||||||||||||||||||
upper limit |
1.59 |
|
|||||||||||||||||||||||||||||
End point title |
The safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with major depressive disorder (MDD) | ||||||||||||||||||||||||||||
End point description |
Assessment of safety and tolerability included adverse events (AEs), clinical laboratory tests (hematology, serum chemistry [including prolactin and glycosylated hemoglobin (HbA1c)], and urinalysis), physical examinations, vital sign measurements, and ECGs. Body weight, height, and waist circumference were also measured.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
At treatment phase (Week 8 or 10 to Week 18/ET visit) and post-treatment follow-up
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Mean Change from End of Phase A to Phase B in SDS scores for all 3 individual item | ||||||||||||||||||||||||||||
End point description |
The SDS is a self-rated instrument used to measure the effect of the subject’s symptoms on work/school, social life, and family/home responsibilities. It was a visual analogue scale which used spatio-visual, numeric, and verbal descriptive anchors to assess disability across 3 domains and the symptom was marked along the line from 0 (not at all) to 10 (extreme). Scores of 5 and above was associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Treatment phase: From Week 8/10 Visit to Week 18/ ET Visit
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Notes [1] - For work/school, number of subjects analyzed was 125 [2] - For work/school, number of subjects analyzed was 67 [3] - For work/school, number of subjects analyzed was 136 |
|||||||||||||||||||||||||||||
Statistical analysis title |
Work/School: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.448 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
0.16
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.25 | ||||||||||||||||||||||||||||
upper limit |
0.56 | ||||||||||||||||||||||||||||
Statistical analysis title |
Work/School: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.038 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
0.52
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
0.03 | ||||||||||||||||||||||||||||
upper limit |
1.02 | ||||||||||||||||||||||||||||
Statistical analysis title |
Social life: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Placebo + ADT v Brexpiprazole + Antidepressant therapy (ADT)
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.0436 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
-0.34
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.66 | ||||||||||||||||||||||||||||
upper limit |
-0.01 | ||||||||||||||||||||||||||||
Statistical analysis title |
Social life: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Placebo + ADT v Quetiapine (Seroquel) extended release (XR) + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.035 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
0.43
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
0.03 | ||||||||||||||||||||||||||||
upper limit |
0.84 | ||||||||||||||||||||||||||||
Statistical analysis title |
Family life: Brexpiprazole +ADT Vs Palcebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Brexpiprazole + Antidepressant therapy (ADT) v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
396
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.0424 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
-0.35
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.69 | ||||||||||||||||||||||||||||
upper limit |
-0.01 | ||||||||||||||||||||||||||||
Statistical analysis title |
Family life: Quetiapine +ADT Vs Placebo + ADT | ||||||||||||||||||||||||||||
Statistical analysis description |
Efficacy Sample: All participants in the Safety Sample who had an end of Phase A (i.e., Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
|
||||||||||||||||||||||||||||
Comparison groups |
Quetiapine (Seroquel) extended release (XR) + ADT v Placebo + ADT
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
304
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.123 | ||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||
Parameter type |
LS mean difference | ||||||||||||||||||||||||||||
Point estimate |
0.33
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.09 | ||||||||||||||||||||||||||||
upper limit |
0.75 |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
At treatment phase (Week 8 or 10 to Week 18/ET visit) and post-treatment follow-up
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
In the safety sample (who received at least 1 dose of double-blind study drug), all AEs with an onset date on or after the start of double-blind treatment; or if the events was continuous from end of phase A and was worsening serious, study drug related, or resulted in death, discontinuation, interruption or reduction of trial therapy.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Brexpiprazole + ADT
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received orally brexpiprazole 1 mg tablet per day and assigned ADT at randomization, and then the dose was increased to 2 mg/day at Day 7 (± 2 days). Subjects remained at the target dose (2 mg/day) unless the investigator requested an increase to a higher dose. Change in the dose was done based on a clinical assessment of the benefit and the subject’s tolerance of the investigational medicinal product (IMP). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Quetiapine (Seroquel) XR + ADT
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Randomized subjects received orally quetiapine XR tablets at a dose of 50 mg/day and assigned ADT therapy on Day 1 and Day 2, and then the dose was increased to 150 mg/day on Day 3 through Day 14. Subjects remained at the target dose (150 mg/day) unless the investigator requested an increase to a higher dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + ADT
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Randomized subjects received orally brexpiprazole or quetiapine matching placebo tablets with the open-label ADT (Phase A) at the final dose reached during the prospective treatment phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
30 Jan 2014 |
Amendment 1:
Clarified necessary trial procedures, inclusion/exclusions criteria and provided updated contact information.
Updated to revise the randomization criteria in the blinded addendum, and to make minor administrative changes to the protocol. |
||
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 |