Trial Outcomes & Findings for Brexpiprazole as Combination Therapy With Sertraline in Treatment of Adults With PTSD (NCT NCT04124614)
NCT ID: NCT04124614
Last Updated: 2025-06-13
Results Overview
CAPS-5 is a structured interview designed to assess PTSD diagnostic status \& symptoms severity as defined by DSM-5. CAPS-5 total score was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from following categories: Category B: Intrusion symptoms (5 items); Category C: Avoidance symptoms (2 items); Category D: Cognition \& mood symptoms (7 items); Category E: Arousal \& reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B, C, D, E. Each symptom was scored 0= Absent to 4= Extreme/incapacitating, yielding a score range of 0-80. Higher scores indicate worse outcome. Least squares (LS) mean was determined by Mixed-effect model repeated measures (MMRM) method with fixed class effect terms for treatment, trial site, visit, previous treatment intervention for PTSD (Yes/No), \& an interaction term of treatment by visit, \& include the interaction term of baseline values of CAPS-5 total score by visit as a covariate.
COMPLETED
PHASE3
450 participants
Baseline (Week 1), Week 10
2025-06-13
Participant Flow
A total of 450 participants took part in the study at 61 investigative sites in the United States from 17 October 2019 to 08 August 2023.
Participants with a diagnosis of post-traumatic stress disorder (PTSD) were first enrolled in a placebo run-in period. At the end of placebo run-in period, participants were randomized in a 1:1 ratio to receive either Brexpiprazole + Sertraline or Sertraline + Placebo in the double-blind treatment (DBT) period.
Participant milestones
| Measure |
Placebo
All enrolled participants received brexpiprazole-matched placebo tablets and sertraline-matched placebo tablets during the 1-week placebo run-in period.
|
Brexpiprazole + Sertraline
Randomized participants received brexpiprazole as a flexible dose 2 milligrams (mg) to 3 mg, orally, once daily (QD) along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
|---|---|---|---|
|
Placebo Run-in Period
STARTED
|
450
|
0
|
0
|
|
Placebo Run-in Period
COMPLETED
|
416
|
0
|
0
|
|
Placebo Run-in Period
NOT COMPLETED
|
34
|
0
|
0
|
|
Double Blind Treatment Period
STARTED
|
0
|
214
|
202
|
|
Double Blind Treatment Period
Randomized Sample
|
0
|
214
|
202
|
|
Double Blind Treatment Period
Enriched Randomized Sample
|
0
|
160
|
150
|
|
Double Blind Treatment Period
FAS Enriched Sample
|
0
|
149
|
137
|
|
Double Blind Treatment Period
Safety Sample
|
0
|
205
|
196
|
|
Double Blind Treatment Period
COMPLETED
|
0
|
137
|
113
|
|
Double Blind Treatment Period
NOT COMPLETED
|
0
|
77
|
89
|
Reasons for withdrawal
| Measure |
Placebo
All enrolled participants received brexpiprazole-matched placebo tablets and sertraline-matched placebo tablets during the 1-week placebo run-in period.
|
Brexpiprazole + Sertraline
Randomized participants received brexpiprazole as a flexible dose 2 milligrams (mg) to 3 mg, orally, once daily (QD) along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
|---|---|---|---|
|
Placebo Run-in Period
Not Randomized
|
34
|
0
|
0
|
|
Double Blind Treatment Period
Adverse Event
|
0
|
7
|
22
|
|
Double Blind Treatment Period
Death
|
0
|
0
|
1
|
|
Double Blind Treatment Period
Lost to Follow-up
|
0
|
18
|
25
|
|
Double Blind Treatment Period
Non-Compliance With Study Drug
|
0
|
5
|
5
|
|
Double Blind Treatment Period
Physician Decision
|
0
|
0
|
3
|
|
Double Blind Treatment Period
Protocol Deviation
|
0
|
10
|
4
|
|
Double Blind Treatment Period
Withdrawal by Subject
|
0
|
26
|
22
|
|
Double Blind Treatment Period
Reason Not Specified
|
0
|
11
|
7
|
Baseline Characteristics
FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score.
Baseline characteristics by cohort
| Measure |
Brexpiprazole + Sertraline
n=214 Participants
Randomized participants received brexpiprazole as a flexible dose 2 mg to 3 mg, orally, QD along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
n=202 Participants
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
Total
n=416 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.8 years
STANDARD_DEVIATION 11.7 • n=214 Participants
|
36.8 years
STANDARD_DEVIATION 12.1 • n=202 Participants
|
37.4 years
STANDARD_DEVIATION 11.9 • n=416 Participants
|
|
Sex: Female, Male
Female
|
158 Participants
n=214 Participants
|
152 Participants
n=202 Participants
|
310 Participants
n=416 Participants
|
|
Sex: Female, Male
Male
|
56 Participants
n=214 Participants
|
50 Participants
n=202 Participants
|
106 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
White
|
147 Participants
n=214 Participants
|
144 Participants
n=202 Participants
|
291 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
50 Participants
n=214 Participants
|
38 Participants
n=202 Participants
|
88 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
7 Participants
n=214 Participants
|
2 Participants
n=202 Participants
|
9 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Participants
n=214 Participants
|
9 Participants
n=202 Participants
|
13 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=214 Participants
|
0 Participants
n=202 Participants
|
1 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=214 Participants
|
2 Participants
n=202 Participants
|
4 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
29 Participants
n=214 Participants
|
32 Participants
n=202 Participants
|
61 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
183 Participants
n=214 Participants
|
167 Participants
n=202 Participants
|
350 Participants
n=416 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 Participants
n=214 Participants
|
1 Participants
n=202 Participants
|
1 Participants
n=416 Participants
|
|
CAPS-5 Total Severity Score
|
38.3 score on a scale
STANDARD_DEVIATION 7.2 • n=149 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score.
|
38.8 score on a scale
STANDARD_DEVIATION 8.0 • n=137 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score.
|
38.6 score on a scale
STANDARD_DEVIATION 7.6 • n=286 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score.
|
|
Clinical Global Impression - Severity (CGI-S) Score
|
4.6 score on a scale
STANDARD_DEVIATION 0.6 • n=148 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Number of participants analyzed is the number of participants with data available for CGI-S score at the Baseline.
|
4.6 score on a scale
STANDARD_DEVIATION 0.6 • n=137 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Number of participants analyzed is the number of participants with data available for CGI-S score at the Baseline.
|
4.6 score on a scale
STANDARD_DEVIATION 0.6 • n=285 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Number of participants analyzed is the number of participants with data available for CGI-S score at the Baseline.
|
|
Brief Inventory of Psychosocial Functions (B-IPF) Score
|
65.2 score on a scale
STANDARD_DEVIATION 21.1 • n=142 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Number of participants analyzed is the number of participants with data available for B-IPF score at the Baseline.
|
64.3 score on a scale
STANDARD_DEVIATION 22.9 • n=129 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Number of participants analyzed is the number of participants with data available for B-IPF score at the Baseline.
|
64.8 score on a scale
STANDARD_DEVIATION 21.9 • n=271 Participants • FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Number of participants analyzed is the number of participants with data available for B-IPF score at the Baseline.
|
PRIMARY outcome
Timeframe: Baseline (Week 1), Week 10Population: FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Overall number analyzed is the number of participants with data available for analysis.
CAPS-5 is a structured interview designed to assess PTSD diagnostic status \& symptoms severity as defined by DSM-5. CAPS-5 total score was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from following categories: Category B: Intrusion symptoms (5 items); Category C: Avoidance symptoms (2 items); Category D: Cognition \& mood symptoms (7 items); Category E: Arousal \& reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B, C, D, E. Each symptom was scored 0= Absent to 4= Extreme/incapacitating, yielding a score range of 0-80. Higher scores indicate worse outcome. Least squares (LS) mean was determined by Mixed-effect model repeated measures (MMRM) method with fixed class effect terms for treatment, trial site, visit, previous treatment intervention for PTSD (Yes/No), \& an interaction term of treatment by visit, \& include the interaction term of baseline values of CAPS-5 total score by visit as a covariate.
Outcome measures
| Measure |
Brexpiprazole + Sertraline
n=148 Participants
Randomized participants received brexpiprazole as a flexible dose 2 mg to 3 mg, orally, QD along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
n=134 Participants
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
|---|---|---|
|
Change From Baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Score
|
-19.19 score on a scale
Standard Error 1.17
|
-13.61 score on a scale
Standard Error 1.24
|
SECONDARY outcome
Timeframe: Baseline (Week 1), Week 10Population: FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Overall number of participants analyzed is the number of participants with data available for analysis.
The CGI-S is a standardized, clinician-administered global rating scale that measures disease severity. To assess it, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices include: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. The score 0 (not assessed) was be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7. A higher score on the CGI-S represents a higher severity of disease. LS mean was determined by MMRM method with fixed class effect terms for treatment, trial site, visit, previous treatment intervention for PTSD (Yes/No), \& an interaction term of treatment by visit, \& include the interaction term of baseline values of CAPS-5 total score by visit as a covariate.
Outcome measures
| Measure |
Brexpiprazole + Sertraline
n=148 Participants
Randomized participants received brexpiprazole as a flexible dose 2 mg to 3 mg, orally, QD along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
n=137 Participants
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
|---|---|---|
|
Change in Clinical Global Impression - Severity (CGI-S) Score
|
-1.54 score on a scale
Standard Error 0.10
|
-1.08 score on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Week 12Population: FAS for Enriched participants included those participants in the Enriched Randomized Sample who received at least 1 dose of double-blind IMP, had a baseline value (Week 1) and at least 1 post baseline efficacy evaluation for CAPS-5 total score. Overall number of participants analyzed is the number of participants with data available for analysis.
The B-IPF is a short patient-reported questionnaire consisting of 7 questions which measure PTSD-specific psychosocial function on a 7-point Likert scale (0 = not at all to 6 = very much, and a not applicable option) with a recall period of 30 days. It measures the concepts of romantic relationships, parenting, family, friendships and socializing, work, education, and self-care. Total score ranges from 0-100 and is calculated by summing the completed scale items, dividing by the maximum possible score of all items and multiplying by 100. Higher scores indicate greater impairment. LS mean was determined by MMRM method with fixed class effect terms for treatment, trial site, visit, previous treatment intervention for PTSD (Yes/No), \& an interaction term of treatment by visit, \& include the interaction term of baseline values of CAPS-5 total score by visit as a covariate.
Outcome measures
| Measure |
Brexpiprazole + Sertraline
n=104 Participants
Randomized participants received brexpiprazole as a flexible dose 2 mg to 3 mg, orally, QD along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
n=97 Participants
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
|---|---|---|
|
Change in Brief Inventory or Psychosocial Functions (B-IPF) Score
|
-33.80 score on a scale
Standard Error 2.84
|
-21.77 score on a scale
Standard Error 2.97
|
Adverse Events
Brexpiprazole + Sertraline
Sertraline + Placebo
Serious adverse events
| Measure |
Brexpiprazole + Sertraline
n=205 participants at risk
Randomized participants received brexpiprazole as a flexible dose 2 mg to 3 mg, orally, QD along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
n=196 participants at risk
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
|---|---|---|
|
Infections and infestations
Diverticulitis
|
0.00%
0/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
0.51%
1/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Infections and infestations
Gastroenteritis
|
0.49%
1/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
0.00%
0/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Injury, poisoning and procedural complications
Toxicity To Various Agents
|
0.00%
0/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
0.51%
1/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Investigations
Hepatic Enzyme Increased
|
0.00%
0/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
0.51%
1/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.00%
0/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
0.51%
1/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
Other adverse events
| Measure |
Brexpiprazole + Sertraline
n=205 participants at risk
Randomized participants received brexpiprazole as a flexible dose 2 mg to 3 mg, orally, QD along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.
|
Sertraline + Placebo
n=196 participants at risk
Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.4%
9/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
6.6%
13/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Gastrointestinal disorders
Nausea
|
12.2%
25/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
11.7%
23/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
General disorders
Fatigue
|
6.8%
14/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
4.1%
8/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Investigations
Weight Increased
|
5.9%
12/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
1.5%
3/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Nervous system disorders
Headache
|
4.9%
10/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
8.7%
17/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Nervous system disorders
Somnolence
|
5.4%
11/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
2.6%
5/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
|
Nervous system disorders
Tremor
|
3.9%
8/205 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
5.1%
10/196 • From the first dose of the study drug up to 21 days after the last dose (Up to Week 15)
Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind IMP.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place