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Trial record 36 of 1923 for:    "Depressive Disorder" [DISEASE] AND Rating AND Major Depressive Disorder AND major

Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (STEP-D222)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01052077
Recruitment Status : Completed
First Posted : January 20, 2010
Results First Posted : November 2, 2015
Last Update Posted : November 2, 2015
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: OPC-34712
Drug: Placebo
Drug: ADT
Enrollment 773
Recruitment Details This trial was conducted in the United States in 773 participants at 44 centers. A total of 1226 participants were screened, 773 participants were enrolled in Phase A, and 769 were treated in Phase A. Of the 623 participants who completed Phase A, 372 participants were randomized in to Phase B.
Pre-assignment Details A 7 to 28-day Screening period, 8-Week single-blind placebo-ADT (antidepressant therapy) prospective Phase, 6-Week double-blind randomization Phase (Phase B), and 30-day follow-up after last dose of medication. Any participant randomized/completed all visits through Week 14 were allowed into an open-label rollover trial (NCT01052077).
Arm/Group Title Phase A Brexiprazole Placebo Phase A+
Hide Arm/Group Description Participants entered a single-blind prospective treatment phase during which they received single-blind placebo plus open-label commercially available ADT for 8 weeks at maximally tolerated doses. Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT. Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT. Participants who met the criteria for a response at the end of the 8 weeks prospective treatment phase received single-blind placebo + ADT for an additional 6 weeks in Phase A+ for a total of 14 weeks.
Period Title: Phase A
Started 769 0 0 0
Completed 623 0 0 0
Not Completed 146 0 0 0
Reason Not Completed
Lost to Follow-up             22             0             0             0
Adverse Event             32             0             0             0
Met Withdrawal Criteria             26             0             0             0
Physician Decision             10             0             0             0
Withdrawal by Subject             29             0             0             0
Protocol Deviation             27             0             0             0
Period Title: Phase B
Started 0 185 187 0
Completed 0 167 171 0
Not Completed 0 18 16 0
Reason Not Completed
Lost to Follow-up             0             2             3             0
Adverse Event             0             9             2             0
Met Withdrawal Criteria             0             2             1             0
Physician Decision             0             1             1             0
Withdrawal by Subject             0             0             5             0
Protocol Deviation             0             3             4             0
Lack of Efficacy             0             1             0             0
Period Title: Phase A+
Started 0 0 0 251
Completed 0 0 0 230
Not Completed 0 0 0 21
Reason Not Completed
Lost to Follow-up             0             0             0             8
Adverse Event             0             0             0             4
Met Withdrawal Criteria             0             0             0             2
Withdrawal by Subject             0             0             0             7
Arm/Group Title Brexpiprazole Placebo Total
Hide Arm/Group Description Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT. Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT. Total of all reporting groups
Overall Number of Baseline Participants 185 187 372
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 185 participants 187 participants 372 participants
44.7  (11.7) 42.4  (11.7) 43.5  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 185 participants 187 participants 372 participants
Female
123
  66.5%
130
  69.5%
253
  68.0%
Male
62
  33.5%
57
  30.5%
119
  32.0%
1.Primary Outcome
Title Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score.
Hide Description The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the Full Analysis Set (FAS) comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-8.20  (0.62) -7.02  (0.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1416
Comments ANCOVA model, with treatment and study center as main effects and Week 8 value as convariate, is used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.18
Confidence Interval (2-Sided) 95%
-2.75 to 0.39
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From End of Phase A (Week 8) to Phase B in Sheehan Disability Scale (SDS) Score.
Hide Description The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all, to 10= extremely. Scores of 5 and above are associated with significant functional impairment. The SDS total score ranges from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 174 172
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-0.91  (0.19) -0.69  (0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3778
Comments ANCOVA model, with treatment and study center as main effects and Week 8 value as covariate, is used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.69 to 0.26
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
Hide Description The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 9 (N= 181, 180) -3.30  (0.42) -1.99  (0.42)
Week 10 (N= 184, 181) -5.92  (0.50) -4.01  (0.50)
Week 11 (N= 184, 181) -7.23  (0.57) -5.22  (0.57)
Week 12 (N= 184, 181) -8.42  (0.59) -6.21  (0.59)
Week 13 (N= 184, 181) -9.00  (0.59) -7.18  (0.59)
Week 14 (N= 184, 181) -8.20  (0.62) -7.02  (0.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0162
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.31
Confidence Interval (2-Sided) 95%
-2.38 to -0.24
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.90
Confidence Interval (2-Sided) 95%
-3.15 to -0.65
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0061
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.01
Confidence Interval (2-Sided) 95%
-3.44 to -0.58
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.21
Confidence Interval (2-Sided) 95%
-3.69 to -0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 13
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0174
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.82
Confidence Interval (2-Sided) 95%
-3.32 to -0.32
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1416
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.18
Confidence Interval (2-Sided) 95%
-2.75 to 0.39
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression- Severity Illness Scale (CGI-S) Score.
Hide Description The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the investigator had to answer the following question: “Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?” Response choices included: 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 participants.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 9 (N= 181, 180) -0.29  (0.05) -0.20  (0.05)
Week 10 (N= 184, 181) -0.58  (0.06) -0.44  (0.06)
Week 11 (N= 184, 181) -0.76  (0.07) -0.59  (0.07)
Week 12 (N= 184, 181) -0.94  (0.07) -0.68  (0.07)
Week 13 (N= 184, 181) -1.00  (0.08) -0.81  (0.08)
Week 14 (N= 184, 181) -0.95  (0.08) -0.85  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1481
Comments ANCOVA model, with treatment and study center as main effects and Week 8 value as covariate, is used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.21 to 0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0691
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.28 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0457
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.35 to -0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0061
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.45 to -0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 13
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0572
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.38 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3318
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.29 to 0.10
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score.
Hide Description The IDS-SR was a 30-item self-report measure, that was used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorder (MDD). For individual items, the scores range from 0 to 3. The IDS-SR are scored by summing responses to 28 of the 30 items to obtain a total score ranging from 0 to 84, higher values indicate greater disruption in the depressive symptoms.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 9 (N= 181, 179) -1.65  (0.54) -1.99  (0.53)
Week 10 (N= 184, 181) -2.91  (0.60) -2.93  (0.60)
Week 11 (N= 184, 181) -3.92  (0.68) -3.64  (0.68)
Week 12 (N= 184, 181) -4.82  (0.74) -4.76  (0.74)
Week 13 (N= 184, 181) -5.60  (0.75) -5.59  (0.75)
Week 14 (N= 184, 181) -5.70  (0.80) -5.84  (0.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6272
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
-1.02 to 1.69
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9697
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-1.48 to 1.54
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7490
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-2.00 to 1.44
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9459
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-1.94 to 1.81
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 13
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9893
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-1.91 to 1.88
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8918
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-1.89 to 2.17
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From End of Phase A (Week 8) to End of Phase B (Week 14) in the Hamilton Depression Rating Scale 17-item Version (HAM-D17) Total Score.
Hide Description The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the “best” rating and the highest score (2 or 4) was the “worst” rating. The possible total scores were from 0 to 52.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 176 172
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-5.98  (0.45) -5.40  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3247
Comments ANCOVA model, with treatment and trial center as main effects and Week 8 value as covariate, was used for change from Week 8 comparisons.
Method ANCOVA
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-1.71 to 0.57
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
Hide Description The efficacy of study medication was rated for each participant using the CGI-I. The study physician would rate the participants total improvement whether or not it is due entirely to drug treatment. Response choices included: 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.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Week 9 (N= 181, 179) 3.33  (0.82) 3.37  (0.74)
Week 10 (N= 184, 180) 3.03  (0.97) 3.15  (0.84)
Week 11 (N= 184, 180) 3.00  (1.08) 3.02  (0.99)
Week 12 (N= 184, 180) 2.63  (1.12) 2.91  (1.02)
Week 13 (N= 184, 180) 2.60  (1.14) 2.80  (1.02)
Week 14 (N= 184, 181) 2.68  (1.18) 2.78  (1.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5616
Comments Cohran-Mantel-Haenszel (CMH) row mean scores differ test controlling for study center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean: brexpiprazole − placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1900
Comments CMH row mean scores differ test controlling for study center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0501
Comments CMH row mean scores differ test controlling for study center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0137
Comments CMH row mean scores differ test controlling for study center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 13
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0711
Comments CMH row mean scores differ test controlling for study center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3438
Comments CMH row mean scores differ test controlling for study center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
8.Secondary Outcome
Title Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
Hide Description A MADRS response was defined as >=50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Measure Type: Number
Unit of Measure: participants
Week 9 (N= 181, 180) 11 4
Week 10 (N= 184, 181) 29 16
Week 11 (N= 184, 181) 41 26
Week 12 (N= 184, 181) 56 28
Week 13 (N= 184, 181) 55 33
Week 14 (N= 184, 181) 55 36
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0679
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Response rate
Estimated Value 2.79
Confidence Interval (2-Sided) 95%
0.88 to 8.81
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0360
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.78
Confidence Interval (2-Sided) 95%
1.01 to 3.14
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0521
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.53
Confidence Interval (2-Sided) 95%
0.99 to 2.35
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.93
Confidence Interval (2-Sided) 95%
1.31 to 2.86
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 13
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
1.14 to 2.38
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0339
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
1.03 to 2.08
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
Hide Description A MADRS remission was defined as MADRS Total Score =< 10 and >= 50 percent reduction in MADRS Total Score from end of Phase A (Week 8 visit). The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The MADRS Total Score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place.
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Measure Type: Number
Unit of Measure: participants
Week 9 (N= 181, 180) 7 3
Week 10 (N= 184, 181) 15 7
Week 11 (N= 184, 181) 31 18
Week 12 (N= 184, 181) 42 19
Week 13 (N= 184, 181) 46 25
Week 14 (N= 184, 181) 48 27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2404
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Remission Rate
Estimated Value 2.27
Confidence Interval (2-Sided) 95%
0.55 to 9.30
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0983
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Remission Rate
Estimated Value 2.04
Confidence Interval (2-Sided) 95%
0.83 to 4.98
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0496
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Remission Rate
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
0.99 to 2.82
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Remission Rate
Estimated Value 2.12
Confidence Interval (2-Sided) 95%
1.31 to 3.46
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 13
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0068
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH general association test controlling for trial center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
1.17 to 2.67
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0089
Comments The CMH general association test controlling for trial center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Ratio of Remission Rate
Estimated Value 1.71
Confidence Interval (2-Sided) 95%
1.14 to 2.57
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
Hide Description CGI-I Response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).
Time Frame Baseline (end of week 8) to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy sample was the FAS comprised of participants who received 1 dose of double-blind study medication and had both end of Week 8 visit value and 1 post-randomization efficacy assessment for MADRS total score in double-blind Phase B. The LOCF method was used to impute missing data.
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description:
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT.
Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
Overall Number of Participants Analyzed 184 181
Measure Type: Number
Unit of Measure: participants
Week 9 (N= 181, 179) 23 19
Week 10 (N= 184, 180) 47 39
Week 11 (N= 184, 180) 73 51
Week 12 (N= 184, 181) 88 63
Week 13 (N= 184, 181) 90 70
Week 14 (N= 184, 181) 84 72
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4605
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.70 to 2.18
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3267
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.83 to 1.72
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 11
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0230
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.37
Confidence Interval (2-Sided) 95%
1.05 to 1.80
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0105
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
1.08 to 1.71
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 13
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0417
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for study center.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
1.01 to 1.58
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
Comments Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2345
Comments CMH general association test controlling for study center.
Method Cochran-Mantel-Haenszel
Comments Treatment difference = difference in adjusted mean change: brexpiprazole − placebo.
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.91 to 1.44
Estimation Comments [Not Specified]
Time Frame AEs were recorded from the time the participant entered Phase B, throughout the 6-week treatment period (Week 9 to Week 14) and until follow-up at 30 days after the last dose of medication.
Adverse Event Reporting Description SAE was any untoward medical occurrence resulting in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. AE was an exacerbation of an existing problem or a new problem experienced by a participant in a trial, whether or not it was drug related. One participant may have experienced multiple events.
 
Arm/Group Title Brexpiprazole Placebo
Hide Arm/Group Description Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to brexpiprazole arm 1 to 3 mg/day, plus the final dosage of the assigned open-label marketed ADT. Participants with an incomplete response at the end of treatment phase (Week 8) were randomized to placebo arm plus the final dosage of the assigned open-label marketed ADT.
All-Cause Mortality
Brexpiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/185 (0.00%)   3/187 (1.60%) 
Cardiac disorders     
Sinus bradycardia * 1  0/185 (0.00%)  1/187 (0.53%) 
Psychiatric disorders     
Depression * 1  0/185 (0.00%)  1/187 (0.53%) 
Vascular disorders     
Hypotension * 1  0/185 (0.00%)  1/187 (0.53%) 
Subclavian vein thrombosis * 1  0/185 (0.00%)  1/187 (0.53%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brexpiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   90/185 (48.65%)   63/187 (33.69%) 
Gastrointestinal disorders     
Constipation * 1  11/185 (5.95%)  4/187 (2.14%) 
Diarrhoea * 1  10/185 (5.41%)  10/187 (5.35%) 
General disorders     
Fatigue * 1  14/185 (7.57%)  8/187 (4.28%) 
Infections and infestations     
Nasopharyngitis * 1  12/185 (6.49%)  5/187 (2.67%) 
Upper respiratory tract infection * 1  9/185 (4.86%)  10/187 (5.35%) 
Investigations     
Weight increased * 1  21/185 (11.35%)  5/187 (2.67%) 
Metabolism and nutrition disorders     
Increased appetite * 1  14/185 (7.57%)  3/187 (1.60%) 
Nervous system disorders     
Akathisia * 1  22/185 (11.89%)  9/187 (4.81%) 
Headache * 1  9/185 (4.86%)  16/187 (8.56%) 
Psychiatric disorders     
Insomnia * 1  17/185 (9.19%)  6/187 (3.21%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
Phone: 800 562-3974
Layout table for additonal information
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01052077     History of Changes
Other Study ID Numbers: 331-09-222
First Submitted: January 15, 2010
First Posted: January 20, 2010
Results First Submitted: August 4, 2015
Results First Posted: November 2, 2015
Last Update Posted: November 2, 2015