Trial Outcomes & Findings for Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (NCT NCT01052077)
NCT ID: NCT01052077
Last Updated: 2015-11-02
Results Overview
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.
COMPLETED
PHASE2
773 participants
Baseline (end of week 8) to Week 14
2015-11-02
Participant Flow
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.
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).
Participant milestones
| Measure |
Phase A
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.
|
Brexiprazole
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.
|
Placebo
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.
|
Phase A+
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.
|
|---|---|---|---|---|
|
Phase A
STARTED
|
769
|
0
|
0
|
0
|
|
Phase A
COMPLETED
|
623
|
0
|
0
|
0
|
|
Phase A
NOT COMPLETED
|
146
|
0
|
0
|
0
|
|
Phase B
STARTED
|
0
|
185
|
187
|
0
|
|
Phase B
COMPLETED
|
0
|
167
|
171
|
0
|
|
Phase B
NOT COMPLETED
|
0
|
18
|
16
|
0
|
|
Phase A+
STARTED
|
0
|
0
|
0
|
251
|
|
Phase A+
COMPLETED
|
0
|
0
|
0
|
230
|
|
Phase A+
NOT COMPLETED
|
0
|
0
|
0
|
21
|
Reasons for withdrawal
| Measure |
Phase A
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.
|
Brexiprazole
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.
|
Placebo
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.
|
Phase A+
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.
|
|---|---|---|---|---|
|
Phase A
Lost to Follow-up
|
22
|
0
|
0
|
0
|
|
Phase A
Adverse Event
|
32
|
0
|
0
|
0
|
|
Phase A
Met Withdrawal Criteria
|
26
|
0
|
0
|
0
|
|
Phase A
Physician Decision
|
10
|
0
|
0
|
0
|
|
Phase A
Withdrawal by Subject
|
29
|
0
|
0
|
0
|
|
Phase A
Protocol Deviation
|
27
|
0
|
0
|
0
|
|
Phase B
Lost to Follow-up
|
0
|
2
|
3
|
0
|
|
Phase B
Adverse Event
|
0
|
9
|
2
|
0
|
|
Phase B
Met Withdrawal Criteria
|
0
|
2
|
1
|
0
|
|
Phase B
Physician Decision
|
0
|
1
|
1
|
0
|
|
Phase B
Withdrawal by Subject
|
0
|
0
|
5
|
0
|
|
Phase B
Protocol Deviation
|
0
|
3
|
4
|
0
|
|
Phase B
Lack of Efficacy
|
0
|
1
|
0
|
0
|
|
Phase A+
Lost to Follow-up
|
0
|
0
|
0
|
8
|
|
Phase A+
Adverse Event
|
0
|
0
|
0
|
4
|
|
Phase A+
Met Withdrawal Criteria
|
0
|
0
|
0
|
2
|
|
Phase A+
Withdrawal by Subject
|
0
|
0
|
0
|
7
|
Baseline Characteristics
Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
Brexpiprazole
n=185 Participants
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.
|
Placebo
n=187 Participants
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
n=372 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44.7 Years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
42.4 Years
STANDARD_DEVIATION 11.7 • n=7 Participants
|
43.5 Years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
123 Participants
n=5 Participants
|
130 Participants
n=7 Participants
|
253 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
62 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
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.
|
-8.20 Units on a scale
Standard Error 0.62
|
-7.02 Units on a scale
Standard Error 0.62
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=174 Participants
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.
|
Placebo
n=172 Participants
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.
|
|---|---|---|
|
Change From End of Phase A (Week 8) to Phase B in Sheehan Disability Scale (SDS) Score.
|
-0.91 Units on a scale
Standard Error 0.19
|
-0.69 Units on a scale
Standard Error 0.19
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
Week 9 (N= 181, 180)
|
-3.30 Units on a scale
Standard Error 0.42
|
-1.99 Units on a scale
Standard Error 0.42
|
|
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
Week 10 (N= 184, 181)
|
-5.92 Units on a scale
Standard Error 0.50
|
-4.01 Units on a scale
Standard Error 0.50
|
|
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
Week 11 (N= 184, 181)
|
-7.23 Units on a scale
Standard Error 0.57
|
-5.22 Units on a scale
Standard Error 0.57
|
|
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
Week 12 (N= 184, 181)
|
-8.42 Units on a scale
Standard Error 0.59
|
-6.21 Units on a scale
Standard Error 0.59
|
|
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
Week 13 (N= 184, 181)
|
-9.00 Units on a scale
Standard Error 0.59
|
-7.18 Units on a scale
Standard Error 0.59
|
|
Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Trial Week Visit in Phase B.
Week 14 (N= 184, 181)
|
-8.20 Units on a scale
Standard Error 0.62
|
-7.02 Units on a scale
Standard Error 0.62
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
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.
Week 9 (N= 181, 180)
|
-0.29 Units on a scale
Standard Error 0.05
|
-0.20 Units on a scale
Standard Error 0.05
|
|
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.
Week 10 (N= 184, 181)
|
-0.58 Units on a scale
Standard Error 0.06
|
-0.44 Units on a scale
Standard Error 0.06
|
|
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.
Week 11 (N= 184, 181)
|
-0.76 Units on a scale
Standard Error 0.07
|
-0.59 Units on a scale
Standard Error 0.07
|
|
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.
Week 12 (N= 184, 181)
|
-0.94 Units on a scale
Standard Error 0.07
|
-0.68 Units on a scale
Standard Error 0.07
|
|
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.
Week 13 (N= 184, 181)
|
-1.00 Units on a scale
Standard Error 0.08
|
-0.81 Units on a scale
Standard Error 0.08
|
|
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.
Week 14 (N= 184, 181)
|
-0.95 Units on a scale
Standard Error 0.08
|
-0.85 Units on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
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.
Week 11 (N= 184, 181)
|
-3.92 Units on a scale
Standard Error 0.68
|
-3.64 Units on a scale
Standard Error 0.68
|
|
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.
Week 12 (N= 184, 181)
|
-4.82 Units on a scale
Standard Error 0.74
|
-4.76 Units on a scale
Standard Error 0.74
|
|
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.
Week 13 (N= 184, 181)
|
-5.60 Units on a scale
Standard Error 0.75
|
-5.59 Units on a scale
Standard Error 0.75
|
|
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.
Week 14 (N= 184, 181)
|
-5.70 Units on a scale
Standard Error 0.80
|
-5.84 Units on a scale
Standard Error 0.80
|
|
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.
Week 9 (N= 181, 179)
|
-1.65 Units on a scale
Standard Error 0.54
|
-1.99 Units on a scale
Standard Error 0.53
|
|
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.
Week 10 (N= 184, 181)
|
-2.91 Units on a scale
Standard Error 0.60
|
-2.93 Units on a scale
Standard Error 0.60
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=176 Participants
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.
|
Placebo
n=172 Participants
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.
|
|---|---|---|
|
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.
|
-5.98 Units on a scale
Standard Error 0.45
|
-5.40 Units on a scale
Standard Error 0.45
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
Week 9 (N= 181, 179)
|
3.33 Units on a scale
Standard Deviation 0.82
|
3.37 Units on a scale
Standard Deviation 0.74
|
|
Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
Week 10 (N= 184, 180)
|
3.03 Units on a scale
Standard Deviation 0.97
|
3.15 Units on a scale
Standard Deviation 0.84
|
|
Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
Week 11 (N= 184, 180)
|
3.00 Units on a scale
Standard Deviation 1.08
|
3.02 Units on a scale
Standard Deviation 0.99
|
|
Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
Week 12 (N= 184, 180)
|
2.63 Units on a scale
Standard Deviation 1.12
|
2.91 Units on a scale
Standard Deviation 1.02
|
|
Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
Week 13 (N= 184, 180)
|
2.60 Units on a scale
Standard Deviation 1.14
|
2.80 Units on a scale
Standard Deviation 1.02
|
|
Clinical Global Impression- Improvement Scale (CGI-I) Score by Study Week in Phase B Relative to End of Phase A.
Week 14 (N= 184, 181)
|
2.68 Units on a scale
Standard Deviation 1.18
|
2.78 Units on a scale
Standard Deviation 1.07
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 9 (N= 181, 180)
|
11 participants
|
4 participants
|
|
Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 10 (N= 184, 181)
|
29 participants
|
16 participants
|
|
Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 11 (N= 184, 181)
|
41 participants
|
26 participants
|
|
Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 12 (N= 184, 181)
|
56 participants
|
28 participants
|
|
Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 13 (N= 184, 181)
|
55 participants
|
33 participants
|
|
Number of Participants With MADRS Response During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 14 (N= 184, 181)
|
55 participants
|
36 participants
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
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.
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 9 (N= 181, 180)
|
7 participants
|
3 participants
|
|
Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 10 (N= 184, 181)
|
15 participants
|
7 participants
|
|
Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 11 (N= 184, 181)
|
31 participants
|
18 participants
|
|
Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 12 (N= 184, 181)
|
42 participants
|
19 participants
|
|
Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 13 (N= 184, 181)
|
46 participants
|
25 participants
|
|
Number of Participants With MADRS Remission During Phase B Relative to the End of Phase A (Week 8) Visit.
Week 14 (N= 184, 181)
|
48 participants
|
27 participants
|
SECONDARY outcome
Timeframe: Baseline (end of week 8) to Week 14Population: 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.
CGI-I Response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).
Outcome measures
| Measure |
Brexpiprazole
n=184 Participants
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.
|
Placebo
n=181 Participants
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.
|
|---|---|---|
|
Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
Week 9 (N= 181, 179)
|
23 participants
|
19 participants
|
|
Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
Week 10 (N= 184, 180)
|
47 participants
|
39 participants
|
|
Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
Week 11 (N= 184, 180)
|
73 participants
|
51 participants
|
|
Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
Week 12 (N= 184, 181)
|
88 participants
|
63 participants
|
|
Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
Week 13 (N= 184, 181)
|
90 participants
|
70 participants
|
|
Number of Participants With CGI-Improvement Response During Phase B Relative to the End of Phase A (Week 8).
Week 14 (N= 184, 181)
|
84 participants
|
72 participants
|
Adverse Events
Brexpiprazole
Placebo
Serious adverse events
| Measure |
Brexpiprazole
n=185 participants at risk
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.
|
Placebo
n=187 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/185 • 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.
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.
|
0.53%
1/187 • 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.
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.
|
|
Psychiatric disorders
Depression
|
0.00%
0/185 • 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.
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.
|
0.53%
1/187 • 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.
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.
|
|
Vascular disorders
Hypotension
|
0.00%
0/185 • 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.
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.
|
0.53%
1/187 • 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.
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.
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.00%
0/185 • 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.
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.
|
0.53%
1/187 • 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.
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.
|
Other adverse events
| Measure |
Brexpiprazole
n=185 participants at risk
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.
|
Placebo
n=187 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
5.9%
11/185 • 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.
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.
|
2.1%
4/187 • 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.
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.4%
10/185 • 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.
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.
|
5.3%
10/187 • 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.
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.
|
|
General disorders
Fatigue
|
7.6%
14/185 • 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.
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.
|
4.3%
8/187 • 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.
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.
|
|
Infections and infestations
Nasopharyngitis
|
6.5%
12/185 • 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.
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.
|
2.7%
5/187 • 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.
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.
|
|
Investigations
Weight increased
|
11.4%
21/185 • 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.
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.
|
2.7%
5/187 • 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.
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.
|
|
Metabolism and nutrition disorders
Increased appetite
|
7.6%
14/185 • 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.
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.
|
1.6%
3/187 • 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.
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.
|
|
Nervous system disorders
Akathisia
|
11.9%
22/185 • 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.
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.
|
4.8%
9/187 • 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.
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.
|
|
Psychiatric disorders
Insomnia
|
9.2%
17/185 • 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.
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.
|
3.2%
6/187 • 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.
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.
|
|
Infections and infestations
Upper respiratory tract infection
|
4.9%
9/185 • 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.
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.
|
5.3%
10/187 • 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.
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.
|
|
Nervous system disorders
Headache
|
4.9%
9/185 • 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.
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.
|
8.6%
16/187 • 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.
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.
|
Additional Information
Global Medical Affairs
Otsuka Pharmaceutical Development and Commercialization, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place