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This will be a 12-week, multicenter, randomized, double-blind trial evaluating the efficacy, safety, and tolerability of brexpiprazole + sertraline combination treatment in adult participants with Post-Traumatic Stress Disorder.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Other | All enrolled participants received brexpiprazole-matched placebo tablets and sertraline-matched placebo tablets during the 1-week placebo run-in period. |
|
| Brexpiprazole + Sertraline | Experimental | 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 double-blind treatment (DBT) period. |
|
| Sertraline + Placebo | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brexpiprazole | Drug | 3 mg pill |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Score | 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. | Baseline (Week 1), Week 10 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Clinical Global Impression - Severity (CGI-S) Score | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding sites, contact 844-687-8522 | San Diego | California | 92103 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39693081 | Derived | Davis LL, Behl S, Lee D, Zeng H, Skubiak T, Weaver S, Hefting N, Larsen KG, Hobart M. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial. JAMA Psychiatry. 2025 Mar 1;82(3):218-227. doi: 10.1001/jamapsychiatry.2024.3996. |
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Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | All enrolled participants received brexpiprazole-matched placebo tablets and sertraline-matched placebo tablets during the 1-week placebo run-in period. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Placebo Run-in Period |
|
| ||||||||||||||||||
| Double Blind Treatment Period |
|
Randomized Sample included all participants randomized into this trial (DBT period).
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| ID | Title | Description |
|---|---|---|
| BG000 | Brexpiprazole + Sertraline | 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. |
| BG001 | Sertraline + Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Score | 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Week 1), Week 10 |
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Brexpiprazole + Sertraline | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diverticulitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Development | Otsuka Pharmaceutical Development & Commercialization, Inc | 1-609-524-6788 | clinicaltransparency@otsuka-us.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 4, 2023 | May 8, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 22, 2023 | May 8, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000591922 | brexpiprazole |
| D020280 | Sertraline |
| ID | Term |
|---|---|
| D015057 | 1-Naphthylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009281 | Naphthalenes |
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| Sertraline | Drug | 150 mg pill |
|
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| Placebo | Other | Pill |
|
| Baseline (Week 1), Week 10 |
| Change in Brief Inventory or Psychosocial Functions (B-IPF) Score | 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. | Baseline (Day 1), Week 12 |
| Enriched Randomized Sample | Enriched Randomized Sample included all participants, randomized satisfying Enriched Participants Criteria, where Enriched Participants Criteria: Clinician-Administered PTSD Scale for Diagnostic & Statistical Manual of Mental Disorders,5th edition [DSM-5] (CAPS-5) total score of at least 27 at randomization visit (Week 1), & an improvement (reduction in CAPS-5 total score) in CAPS-5 total score of less than 50% at end of placebo run-in phase (from baseline to randomization visit [Week 1]). |
|
| FAS Enriched Sample | 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. |
|
| Safety Sample | Safety Sample included all participants in the randomized sample who were administered at least one dose of double-blind investigational medicinal product (IMP). |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| CAPS-5 Total Severity Score | CAPS-5=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). Each symptom was scored 0=Absent to 4=Extreme/incapacitating, yielding a score range of 0-80. Higher scores indicate worse outcome. | 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. | Mean | Standard Deviation | score on a scale |
|
| Clinical Global Impression - Severity (CGI-S) Score | CGI-S=standardized clinician-administered global rating scale measuring disease severity. To assess CGI-S, rater/investigator answered following question:"Considering your total clinical experience with this particular population,how mentally ill is 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; & 7=among most extremely ill participants. Score 0 (not assessed) was to be set to missing. CGI-S is a 7-point scale from 1-7. Higher score =higher disease severity. | 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. | Mean | Standard Deviation | score on a scale |
|
| Brief Inventory of Psychosocial Functions (B-IPF) Score | 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. | 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. | Mean | Standard Deviation | score on a scale |
|
|
|
|
|
| Secondary | Change in Clinical Global Impression - Severity (CGI-S) Score | 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Week 1), Week 10 |
|
|
|
|
| Secondary | Change in Brief Inventory or Psychosocial Functions (B-IPF) Score | 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Day 1), Week 12 |
|
|
|
|
| 0 |
| 205 |
| 1 |
| 205 |
| 68 |
| 205 |
| EG001 | 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. | 1 | 196 | 4 | 196 | 58 | 196 |
| Gastroenteritis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Toxicity To Various Agents | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
|
| Hepatic Enzyme Increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Cerebrovascular Accident | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Weight Increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
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| D011084 |
| Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |