Stress Disorders, Post-TraumaticPhase 2NCT03033069

A Study of Flexible Dose Brexpiprazole as Monotherapy or Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder (PTSD)

A Phase 2 study testing Brexpiprazole and Sertraline in people with Stress Disorders, Post-Traumatic, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 54 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

To evaluate the safety, efficacy and tolerability of brexpiprazole (with placebo) as monotherapy or combination therapy with Zoloft (sertraline) in adults with PTSD. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Stress Disorders, Post-Traumatic
What is being tested?: Brexpiprazole and Sertraline
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 336 participants
Where: 54 sitesUnited States
Study dates: 26 Jan 2017to 12 Nov 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female participants between the years of 18-65 with a diagnosis of PTSD (diagnosis can be made at screening)

Who cannot join

Index trauma event >15 years before screening
Index trauma event at age <16
Any traumatic event within 3 months of screening

Trial locations and contacts

54 sites in 1 country.

City, postcode or hospital

54 sites in 1 country

United States54 sites

Investigational Site
Atlanta, Georgia, 30341
Investigational Site
Bellaire, Texas, 77401
Investigational Site
Bellflower, California, 90706
Investigational Site
Berlin, New Jersey, 08009
Investigational Site
Beverly Hills, California, 90210
Investigational Site
Bradenton, Florida, 34201
Investigational Site
Brooklyn, New York, 11235
Investigational Site
Cedarhurst, New York, 11516
Investigational Site
Charleston, South Carolina, 29401
Investigational Site
Charlotte, North Carolina, 28211
Investigational Site
Chicago, Illinois, 60640
Investigational Site
Cincinnati, Ohio, 45215
Investigational Site
Colorado Springs, Colorado, 80910
Investigational Site
Decatur, Georgia, 30030
Investigational Site
Everett, Washington, 98201
Investigational Site
Fort Lauderdale, Florida, 33319
Investigational Site
Fort Myers, Florida, 33912
Investigational Site
Gainesville, Florida, 32607
Investigational Site
Glendale, California, 91206
Investigational Site
Jacksonville, Florida, 32256
Investigational Site
Las Vegas, Nevada, 89102
Investigational Site
Lincoln, Rhode Island, 02865
Investigational Site
Little Rock, Arkansas, 72211
Investigational Site
Media, Pennsylvania, 19063
Investigational Site
Memphis, Tennessee, 38119
Investigational Site
National City, California, 91950
Investigational Site
New York, New York, 10128
Investigational Site
Norristown, Pennsylvania, 19403
Investigational Site
North Miami, Florida, 33161
Investigational Site
Oceanside, California, 92054
Investigational Site
Oceanside, California, 92056
Investigational Site
Oklahoma City, Oklahoma, 73103
Investigational Site
Oklahoma City, Oklahoma, 73118
Investigational Site
Orange, California, 92868
Investigational Site
Orlando, Florida, 32801
Investigational Site
Orlando, Florida, 32806
Investigational Site
Phoenix, Arizona, 85032
Investigational Site
Portland, Oregon, 97214
Investigational Site
Princeton, New Jersey, 08540
Investigational Site
Raleigh, North Carolina, 27609
Investigational Site
Redlands, California, 92374
Investigational Site
Riverside, California, 92506
Investigational Site
Rochester, New York, 14618
Investigational Site
Rogers, Arkansas, 72758
Investigational Site
Roswell, Georgia, 30076
Investigational Site
Salem, Oregon, 97301
Investigational Site
San Antonio, Texas, 78229
Investigational Site
San Diego, California, 92103
Investigational Site
San Marcos, California, 92078
Investigational Site
St Louis, Missouri, 63141
Investigational Site
Tampa, Florida, 33614
Investigational Site
Torrance, California, 90502
Investigational Site
Tuscaloosa, Alabama, 35404
Investigational Site
Wichita Falls, Texas, 76309

Other trials in United States

About this study

Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo- and Active-controlled Trial of Brexpiprazole (1 - 3 mg/Day) as Monotherapy or as Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder

To evaluate the safety, efficacy and tolerability of brexpiprazole (with placebo) as monotherapy or combination therapy with Zoloft (sertraline) in adults with PTSD.

Read the detailed description

This trial is designed to assess the efficacy, safety and tolerability of flexible dose brexpiprazole as monotherapy or as combination therapy with Zoloft (Sertraline) in adult participants with PTSD.

This study will consist of a continuous 12-week, double-blind treatment period with a 14-day follow-up.

Conditions: Stress Disorders, Post-Traumatic
Being tested: Brexpiprazole, Sertraline, Brexpiprazole Matching Placebo, Sertraline Matching Placebo
Medical subject headings: Stress Disorders, Post-Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BrexpiprazoleDrug
Also called OPC-34712, OPC-331
Brexpiprazole oral tablets.
SertralineDrug
Also called Zoloft
Sertraline oral capsules.
Brexpiprazole Matching PlaceboDrug
Brexpiprazole matching placebo oral tablets.
Sertraline Matching PlaceboDrug
Sertraline matching placebo oral capsules.

Study groups in NCT03033069
Study group	Role	What they receive
Brexpiprazole + Sertraline	Experimental	Participants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12. Receives: Drug: Brexpiprazole; Drug: Sertraline; Drug: Sertraline Matching Placebo
Brexpiprazole	Experimental	Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12. Receives: Drug: Brexpiprazole; Drug: Sertraline Matching Placebo
Sertraline	Active comparator	Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12. Receives: Drug: Sertraline; Drug: Brexpiprazole Matching Placebo; Drug: Sertraline Matching Placebo
Placebo	Placebo comparator	Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12. Receives: Drug: Brexpiprazole Matching Placebo; Drug: Sertraline Matching Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score
CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 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 with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.
Measured: Baseline, Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Jan 201712 Nov 2018

First posted26 Jan 2017 (estimated)
Study start26 Jan 2017
Primary completion12 Nov 2018
Study completion12 Nov 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Stress Disorders, Post-TraumaticStudies of the same condition, open and under way.
More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 336 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03033069
Sponsor's protocol ID: 331-201-00061
Status last verified: Nov 2021
First submitted: 24 Jan 2017
Last updated: 8 Dec 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

Hobart M, Chang D, Hefting N, Davis LL. Brexpiprazole in Combination With Sertraline and as Monotherapy in Posttraumatic Stress Disorder: A Full-Factorial Randomized Clinical Trial. J Clin Psychiatry. 2025 Feb 19;86(1):24m15577. doi: 10.4088/JCP.24m15577.
PubMed 40009045

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Not yet recruiting
A Transdiagnostic Sleep Health Intervention for Veterans With PTSD
Stress Disorders, Post-Traumatic, Sleep Initiation and Maintenance Disorders
Not yet recruitingPhase 3
Women Who Are Victims of Violence: Treatment of PTSD Through Reactivation of Traumatic Memories Using Propranolol
Post-Traumatic Stress Disorder, PTSD
RecruitingPhase 4
The Effects of Orexin Antagonism on Fear Extinction in PTSD
Insomnia, PTSD
Recruiting
Advancing Skills Through Consultation, Education, and Novel Technologies
PTSD - Post Traumatic Stress Disorder

All Stress Disorders, Post-Traumatic trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo- and Active-controlled Trial of Brexpiprazole (1 - 3 mg/Day) as Monotherapy or as Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder
ClinicalTrials.gov ID: NCT03033069
Acronym / sponsor ID: 331-201-00061
Conditions: Stress Disorders, Post-Traumatic
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 336 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
Collaborators: H. Lundbeck A/S
Study start: 26 Jan 2017 (actual)
Primary completion: 12 Nov 2018 (actual)
Study completion: 12 Nov 2018 (actual)
First posted: 26 Jan 2017 (estimated)
Results: Posted 8 Dec 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To evaluate the safety, efficacy and tolerability of brexpiprazole (with placebo) as monotherapy or combination therapy with Zoloft (sertraline) in adults with PTSD.

Detailed description

This study will consist of a continuous 12-week, double-blind treatment period with a 14-day follow-up.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Brexpiprazole + Sertraline	Experimental	Drug: Brexpiprazole, Drug: Sertraline, Drug: Sertraline Matching PlaceboParticipants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.
Brexpiprazole	Experimental	Drug: Brexpiprazole, Drug: Sertraline Matching PlaceboParticipants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.
Sertraline	Active comparator	Drug: Sertraline, Drug: Brexpiprazole Matching Placebo, Drug: Sertraline Matching PlaceboParticipants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.
Placebo	Placebo comparator	Drug: Brexpiprazole Matching Placebo, Drug: Sertraline Matching PlaceboParticipants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Male and female participants between the years of 18-65 with a diagnosis of PTSD (diagnosis can be made at screening)

Key exclusion criteria (3 listed)

Index trauma event >15 years before screening
Index trauma event at age <16
Any traumatic event within 3 months of screening

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BrexpiprazoleAlso: OPC-34712, OPC-331Brexpiprazole oral tablets.	Drug	Brexpiprazole, Brexpiprazole + Sertraline
SertralineAlso: ZoloftSertraline oral capsules.	Drug	Brexpiprazole + Sertraline, Sertraline
Brexpiprazole Matching PlaceboBrexpiprazole matching placebo oral tablets.	Drug	Placebo, Sertraline
Sertraline Matching PlaceboSertraline matching placebo oral capsules.	Drug	Brexpiprazole, Brexpiprazole + Sertraline, Placebo, Sertraline

Primary outcome

Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score
Time frame: Baseline, Week 12
CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 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 with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.

Results and safety

Results posted to the registry on 8 Dec 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Brexpiprazole + Sertraline	82	58
Brexpiprazole	75	50
Sertraline	81	59
Placebo	83	64

Primary outcome: Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score

Time frame: Baseline, Week 12. Least squares mean (Standard Error). Unit: score on a scale

Measure	Brexpiprazole + Sertraline n = 59	Brexpiprazole n = 48	Sertraline n = 58	Placebo n = 62
Value	-16.4 (1.43)	-12.2 (1.57)	-11.4 (1.46)	-10.5 (1.40)

Brexpiprazole + Sertraline vs Placebo: Least Squares (LS ) Mean Difference: -5.99 (95% CI -9.79 to -2.19), p =0.0021, Mixed Model Repeated Measures (MMRM)
Brexpiprazole vs Placebo: LS Mean Difference: -1.74 (95% CI -5.70 to 2.22), p =0.3868, MMRM
Sertraline vs Placebo: LS Mean Difference: -0.91 (95% CI -4.74 to 2.92), p =0.6399, MMRM

Population analysed: ITT Sample included all participants who were randomized in the trial and took at least one dose of double-blind investigational medicinal product (IMP) and have a Baseline and at least one post Baseline evaluation for the CAPS-5 total score. Overall number of participants analyzed are the number of participants with data available for analyses.

Adverse events

Time frame: From the first dose of the study drug up to 14 days after the last dose (Up to Week 14). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Brexpiprazole + Sertraline	2 of 80 (2.5%)	47 of 80 (58.8%)	0 of 80
Brexpiprazole	1 of 75 (1.3%)	42 of 75 (56%)	0 of 75
Sertraline	0 of 79 (0%)	46 of 79 (58.2%)	0 of 79
Placebo	4 of 82 (4.9%)	43 of 82 (52.4%)	1 of 82

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40009045Hobart M, Chang D, Hefting N, Davis LL. Brexpiprazole in Combination With Sertraline and as Monotherapy in Posttraumatic Stress Disorder: A Full-Factorial Randomized Clinical Trial. J Clin Psychiatry. 2025 Feb 19;86(1):24m15577. doi: 10.4088/JCP.24m15577.
Individual participant dataSharing planned: Yes. 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.

Related trials for Stress Disorders, Post-Traumatic

Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Not yet recruiting
A Transdiagnostic Sleep Health Intervention for Veterans With PTSD
Stress Disorders, Post-Traumatic, Sleep Initiation and Maintenance Disorders
Not yet recruitingPhase 3
Women Who Are Victims of Violence: Treatment of PTSD Through Reactivation of Traumatic Memories Using Propranolol
Post-Traumatic Stress Disorder, PTSD
RecruitingPhase 4
The Effects of Orexin Antagonism on Fear Extinction in PTSD
Insomnia, PTSD
Recruiting
Advancing Skills Through Consultation, Education, and Novel Technologies
PTSD - Post Traumatic Stress Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

54 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brexpiprazole and Sertraline in people with Stress Disorders, Post-Traumatic, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 54 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score (time frame: Baseline, Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03033069, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2021.