Trial Outcomes & Findings for Brexpiprazole as Combination Therapy With Sertraline in the Treatment of Adults With Post-traumatic Stress Disorder (NCT NCT04174170)

Last Updated: 2025-05-30

Results Overview

CAPS-5 was a structured interview designed to assess PTSD diagnostic status and 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 categories: Category B: Intrusion symptoms (5 items); Category C: Avoidance symptoms (2 items); Category D: Cognition and mood symptoms (7 items); Category E: Arousal and 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, to yield 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 effect of treatment, trial site, visit week, and an interaction term of treatment by visit week, and included the interaction term of baseline values by visit week as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

591 participants

Primary outcome timeframe

Baseline (Week 1), Week 10

Results posted on

2025-05-30

Participant Flow

A total of 591 participants took part in the study at 75 investigative sites in the United States from 30 October 2019 to 15 August 2023.

Participants with a diagnosis of post-traumatic stress disorder (PTSD) were first enrolled in a 1-week placebo run-in period. At the end of placebo run-in period, participants were randomized in a 1:1:1 ratio to receive a combination of Brexpiprazole (2 \[milligrams\]mg/day) + Sertraline, Brexpiprazole (3 mg/day) + Sertraline or Sertraline + Placebo in the double-blind treatment (DBT) period.

Participant milestones

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 (2 mg) + Sertraline Randomized participants received brexpiprazole 2 mg, orally, once daily (QD) in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo Randomized participants received sertraline 150 mg, orally, QD, in combination with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
Placebo Run-in Period STARTED	591	0	0	0
Placebo Run-in Period COMPLETED	553	0	0	0
Placebo Run-in Period NOT COMPLETED	38	0	0	0
Double Blind Treatment Period STARTED	0	191	185	177
Double Blind Treatment Period Randomized Sample	0	191	185	177
Double Blind Treatment Period Enriched Randomized Sample	0	143	136	138
Double Blind Treatment Period Full Analysis Set (FAS) Enriched Sample	0	132	126	130
Double Blind Treatment Period Safety Sample	0	185	180	172
Double Blind Treatment Period COMPLETED	0	126	123	116
Double Blind Treatment Period NOT COMPLETED	0	65	62	61

Reasons for withdrawal

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 (2 mg) + Sertraline Randomized participants received brexpiprazole 2 mg, orally, once daily (QD) in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo Randomized participants received sertraline 150 mg, orally, QD, in combination with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
Placebo Run-in Period Not Randomized	38	0	0	0
Double Blind Treatment Period Adverse Event	0	9	9	8
Double Blind Treatment Period Death	0	1	0	0
Double Blind Treatment Period Lost to Follow-up	0	22	11	25
Double Blind Treatment Period Non-Compliance With Study Drug	0	4	4	2
Double Blind Treatment Period Physician Decision	0	1	0	1
Double Blind Treatment Period Pregnancy	0	1	0	1
Double Blind Treatment Period Protocol Deviation	0	7	6	4
Double Blind Treatment Period Withdrawal by Subject	0	19	29	14
Double Blind Treatment Period Reason Not Specified	0	1	3	6

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

Baseline characteristics by cohort
Measure	Brexpiprazole (2 mg) + Sertraline n=191 Participants Randomized participants received brexpiprazole 2 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline n=185 Participants Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo n=177 Participants Randomized participants received sertraline 150 mg, orally, QD, in combination with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.	Total n=553 Participants Total of all reporting groups
Age, Continuous	37.1 years STANDARD_DEVIATION 12.1 • n=191 Participants	36.3 years STANDARD_DEVIATION 11.7 • n=185 Participants	37.7 years STANDARD_DEVIATION 12.3 • n=177 Participants	37.0 years STANDARD_DEVIATION 12.1 • n=553 Participants
Sex: Female, Male Female	142 Participants n=191 Participants	141 Participants n=185 Participants	126 Participants n=177 Participants	409 Participants n=553 Participants
Sex: Female, Male Male	49 Participants n=191 Participants	44 Participants n=185 Participants	51 Participants n=177 Participants	144 Participants n=553 Participants
Race/Ethnicity, Customized Hispanic or Latino	48 Participants n=191 Participants	37 Participants n=185 Participants	37 Participants n=177 Participants	122 Participants n=553 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	143 Participants n=191 Participants	146 Participants n=185 Participants	140 Participants n=177 Participants	429 Participants n=553 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=191 Participants	1 Participants n=185 Participants	0 Participants n=177 Participants	1 Participants n=553 Participants
Race/Ethnicity, Customized Other	4 Participants n=191 Participants	6 Participants n=185 Participants	5 Participants n=177 Participants	15 Participants n=553 Participants
Race/Ethnicity, Customized White	130 Participants n=191 Participants	124 Participants n=185 Participants	121 Participants n=177 Participants	375 Participants n=553 Participants
Race/Ethnicity, Customized Black or African American	46 Participants n=191 Participants	45 Participants n=185 Participants	44 Participants n=177 Participants	135 Participants n=553 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=191 Participants	1 Participants n=185 Participants	2 Participants n=177 Participants	6 Participants n=553 Participants
Race/Ethnicity, Customized Asian	6 Participants n=191 Participants	8 Participants n=185 Participants	5 Participants n=177 Participants	19 Participants n=553 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=191 Participants	1 Participants n=185 Participants	0 Participants n=177 Participants	3 Participants n=553 Participants
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Score	38.8 score on a scale STANDARD_DEVIATION 8.3 • n=132 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.	37.8 score on a scale STANDARD_DEVIATION 7.3 • n=126 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.	39.3 score on a scale STANDARD_DEVIATION 7.8 • n=130 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.	38.7 score on a scale STANDARD_DEVIATION 7.8 • n=388 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 0.7 • n=132 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.	4.5 score on a scale STANDARD_DEVIATION 0.7 • n=124 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.	4.7 score on a scale STANDARD_DEVIATION 0.7 • 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 CGI-S score at the Baseline.	4.6 score on a scale STANDARD_DEVIATION 0.7 • n=385 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	63.3 score on a scale STANDARD_DEVIATION 20.1 • n=125 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.	62.5 score on a scale STANDARD_DEVIATION 22.4 • n=118 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.	59.9 score on a scale STANDARD_DEVIATION 20.5 • n=124 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.	61.9 score on a scale STANDARD_DEVIATION 21.0 • n=367 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 10

Population: 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.

Outcome measures

Outcome measures
Measure	Brexpiprazole (2 mg) + Sertraline n=132 Participants Randomized participants received brexpiprazole 2 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline n=124 Participants Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo n=130 Participants Randomized participants received sertraline 150 mg, orally, QD, in combination 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	-16.53 score on a scale Standard Error 1.19	-18.28 score on a scale Standard Error 1.23	-17.57 score on a scale Standard Error 1.19

SECONDARY outcome

Timeframe: Baseline (Week 1), Week 10

Population: 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 CGI-S, 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 to 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 effect of treatment, trial site, visit week, and an interaction term of treatment by visit week, and included the interaction term of baseline values by visit week as a covariate.

Outcome measures

Outcome measures
Measure	Brexpiprazole (2 mg) + Sertraline n=132 Participants Randomized participants received brexpiprazole 2 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline n=124 Participants Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo n=129 Participants Randomized participants received sertraline 150 mg, orally, QD, in combination 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	-1.26 score on a scale Standard Error 0.10	-1.31 score on a scale Standard Error 0.11	-1.29 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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. The B-IPF 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 effect of treatment, trial site, visit week, and an interaction term of treatment by visit week, and included the interaction term of baseline values by visit week as a covariate.

Outcome measures

Outcome measures
Measure	Brexpiprazole (2 mg) + Sertraline n=98 Participants Randomized participants received brexpiprazole 2 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline n=94 Participants Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo n=96 Participants Randomized participants received sertraline 150 mg, orally, QD, in combination with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
Change in Brief Inventory of Psychosocial Functions (B-IPF) Score	-27.12 score on a scale Standard Error 2.67	-31.79 score on a scale Standard Error 2.86	-22.96 score on a scale Standard Error 2.71

Adverse Events

Brexpiprazole (2 mg) + Sertraline

Serious events: 1 serious events

Other events: 31 other events

Deaths: 1 deaths

Brexpiprazole (3 mg) + Sertraline

Serious events: 1 serious events

Other events: 35 other events

Deaths: 0 deaths

Sertraline + Placebo

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brexpiprazole (2 mg) + Sertraline n=185 participants at risk Randomized participants received brexpiprazole 2 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline n=180 participants at risk Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo n=172 participants at risk Randomized participants received sertraline 150 mg, orally, QD, in combination with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
General disorders Cyst Rupture	0.00% 0/185 • 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.	0.56% 1/180 • 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% 0/172 • 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 Drowning	0.54% 1/185 • 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% 0/180 • 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% 0/172 • 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.
Psychiatric disorders Mania	0.00% 0/185 • 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% 0/180 • 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.	0.58% 1/172 • 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.
Psychiatric disorders Suicidal Ideation	0.00% 0/185 • 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% 0/180 • 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.	0.58% 1/172 • 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.
Vascular disorders Hypertension	0.00% 0/185 • 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% 0/180 • 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.	0.58% 1/172 • 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

Other adverse events
Measure	Brexpiprazole (2 mg) + Sertraline n=185 participants at risk Randomized participants received brexpiprazole 2 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Brexpiprazole (3 mg) + Sertraline n=180 participants at risk Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.	Sertraline + Placebo n=172 participants at risk Randomized participants received sertraline 150 mg, orally, QD, in combination with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.
Gastrointestinal disorders Diarrhoea	3.8% 7/185 • 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.	6.1% 11/180 • 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.	6.4% 11/172 • 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	4.9% 9/185 • 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.	8.3% 15/180 • 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% 15/172 • 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	7.0% 13/185 • 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.	5.6% 10/180 • 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.	7.6% 13/172 • 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.
Psychiatric disorders Insomnia	3.8% 7/185 • 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.	3.9% 7/180 • 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.	5.2% 9/172 • 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

Phone: +1-609-524-6788

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place