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

Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03033069
Collaborator
H. Lundbeck A/S (Industry)
336
54
4
21.5
6.2
0.3

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
336 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 26, 2017
Actual Primary Completion Date :
Nov 12, 2018
Actual Study Completion Date :
Nov 12, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Brexpiprazole + Sertraline

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.

Drug: Brexpiprazole
Brexpiprazole oral tablets.
Other Names:
  • OPC-34712
  • OPC-331
  • Drug: Sertraline
    Sertraline oral capsules.
    Other Names:
  • Zoloft
  • Drug: Sertraline Matching Placebo
    Sertraline matching placebo oral capsules.

    Experimental: Brexpiprazole

    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.

    Drug: Brexpiprazole
    Brexpiprazole oral tablets.
    Other Names:
  • OPC-34712
  • OPC-331
  • Drug: Sertraline Matching Placebo
    Sertraline matching placebo oral capsules.

    Active Comparator: Sertraline

    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.

    Drug: Sertraline
    Sertraline oral capsules.
    Other Names:
  • Zoloft
  • Drug: Brexpiprazole Matching Placebo
    Brexpiprazole matching placebo oral tablets.

    Drug: Sertraline Matching Placebo
    Sertraline matching placebo oral capsules.

    Placebo Comparator: Placebo

    Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.

    Drug: Brexpiprazole Matching Placebo
    Brexpiprazole matching placebo oral tablets.

    Drug: Sertraline Matching Placebo
    Sertraline matching placebo oral capsules.

    Outcome Measures

    Primary Outcome Measures

    1. 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 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male and female participants between the years of 18-65 with a diagnosis of PTSD (diagnosis can be made at screening)
    Exclusion Criteria:
    • Index trauma event >15 years before screening

    • Index trauma event at age <16

    • Any traumatic event within 3 months of screening

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Investigational Site Tuscaloosa Alabama United States 35404
    2 Investigational Site Phoenix Arizona United States 85032
    3 Investigational Site Little Rock Arkansas United States 72211
    4 Investigational Site Rogers Arkansas United States 72758
    5 Investigational Site Bellflower California United States 90706
    6 Investigational Site Beverly Hills California United States 90210
    7 Investigational Site Glendale California United States 91206
    8 Investigational Site National City California United States 91950
    9 Investigational Site Oceanside California United States 92054
    10 Investigational Site Oceanside California United States 92056
    11 Investigational Site Orange California United States 92868
    12 Investigational Site Redlands California United States 92374
    13 Investigational Site Riverside California United States 92506
    14 Investigational Site San Diego California United States 92103
    15 Investigational Site San Marcos California United States 92078
    16 Investigational Site Torrance California United States 90502
    17 Investigational Site Colorado Springs Colorado United States 80910
    18 Investigational Site Bradenton Florida United States 34201
    19 Investigational Site Fort Lauderdale Florida United States 33319
    20 Investigational Site Fort Myers Florida United States 33912
    21 Investigational Site Gainesville Florida United States 32607
    22 Investigational Site Jacksonville Florida United States 32256
    23 Investigational Site North Miami Florida United States 33161
    24 Investigational Site Orlando Florida United States 32801
    25 Investigational Site Orlando Florida United States 32806
    26 Investigational Site Tampa Florida United States 33614
    27 Investigational Site Atlanta Georgia United States 30341
    28 Investigational Site Decatur Georgia United States 30030
    29 Investigational Site Roswell Georgia United States 30076
    30 Investigational Site Chicago Illinois United States 60640
    31 Investigational Site Saint Louis Missouri United States 63141
    32 Investigational Site Las Vegas Nevada United States 89102
    33 Investigational Site Berlin New Jersey United States 08009
    34 Investigational Site Princeton New Jersey United States 08540
    35 Investigational Site Brooklyn New York United States 11235
    36 Investigational Site Cedarhurst New York United States 11516
    37 Investigational Site New York New York United States 10128
    38 Investigational Site Rochester New York United States 14618
    39 Investigational Site Charlotte North Carolina United States 28211
    40 Investigational Site Raleigh North Carolina United States 27609
    41 Investigational Site Cincinnati Ohio United States 45215
    42 Investigational Site Oklahoma City Oklahoma United States 73103
    43 Investigational Site Oklahoma City Oklahoma United States 73118
    44 Investigational Site Portland Oregon United States 97214
    45 Investigational Site Salem Oregon United States 97301
    46 Investigational Site Media Pennsylvania United States 19063
    47 Investigational Site Norristown Pennsylvania United States 19403
    48 Investigational Site Lincoln Rhode Island United States 02865
    49 Investigational Site Charleston South Carolina United States 29401
    50 Investigational Site Memphis Tennessee United States 38119
    51 Investigational Site Bellaire Texas United States 77401
    52 Investigational Site San Antonio Texas United States 78229
    53 Investigational Site Wichita Falls Texas United States 76309
    54 Investigational Site Everett Washington United States 98201

    Sponsors and Collaborators

    • Otsuka Pharmaceutical Development & Commercialization, Inc.
    • H. Lundbeck A/S

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Otsuka Pharmaceutical Development & Commercialization, Inc.
    ClinicalTrials.gov Identifier:
    NCT03033069
    Other Study ID Numbers:
    • 331-201-00061
    First Posted:
    Jan 26, 2017
    Last Update Posted:
    Dec 8, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants took part in the study at 48 investigative sites in the United States from 26 January 2017 to 12 November 2018.
    Pre-assignment Detail Of the 336 participants enrolled in the study, 321 participants diagnosed with post-traumatic stress disorder (PTSD) were randomized in 1:1:1:1 ratio to receive brexpiprazole monotherapy, brexpiprazole plus sertraline combination therapy, sertraline monotherapy or placebo up to Week 12.
    Arm/Group Title Brexpiprazole + Sertraline Brexpiprazole Sertraline Placebo
    Arm/Group Description 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. 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. 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. Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
    Period Title: Overall Study
    STARTED 82 75 81 83
    Safety Sample 80 75 79 82
    Intent to Treat (ITT) Sample 79 72 77 80
    COMPLETED 58 50 59 64
    NOT COMPLETED 24 25 22 19

    Baseline Characteristics

    Arm/Group Title Brexpiprazole + Sertraline Brexpiprazole Sertraline Placebo Total
    Arm/Group Description Participants were administered oral brexpiprazole initial dose of 0.5 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. 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. 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. Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week12. Total of all reporting groups
    Overall Participants 82 75 81 83 321
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38.4
    (11.9)
    39.3
    (10.6)
    38.6
    (10.9)
    40.3
    (11.0)
    39.2
    (11.1)
    Sex: Female, Male (Count of Participants)
    Female
    51
    62.2%
    49
    65.3%
    51
    63%
    48
    57.8%
    199
    62%
    Male
    31
    37.8%
    26
    34.7%
    30
    37%
    35
    42.2%
    122
    38%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    1
    1.2%
    1
    1.3%
    0
    0%
    2
    2.4%
    4
    1.2%
    Asian
    1
    1.2%
    2
    2.7%
    0
    0%
    1
    1.2%
    4
    1.2%
    Native Hawaiian or Other Pacific Islander
    1
    1.2%
    1
    1.3%
    0
    0%
    0
    0%
    2
    0.6%
    Black or African American
    21
    25.6%
    23
    30.7%
    22
    27.2%
    26
    31.3%
    92
    28.7%
    White
    55
    67.1%
    43
    57.3%
    53
    65.4%
    46
    55.4%
    197
    61.4%
    Other
    3
    3.7%
    5
    6.7%
    6
    7.4%
    8
    9.6%
    22
    6.9%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    13
    15.9%
    11
    14.7%
    11
    13.6%
    14
    16.9%
    49
    15.3%
    Not Hispanic or Latino
    68
    82.9%
    64
    85.3%
    70
    86.4%
    69
    83.1%
    271
    84.4%
    Other
    1
    1.2%
    0
    0%
    0
    0%
    0
    0%
    1
    0.3%
    Region of Enrollment (Count of Participants)
    United States
    82
    100%
    75
    100%
    81
    100%
    83
    100%
    321
    100%

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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.
    Time Frame Baseline, Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Brexpiprazole + Sertraline Brexpiprazole Sertraline Placebo
    Arm/Group Description Participants were administered oral brexpiprazole initial dose of 0.5 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. 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. 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. Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
    Measure Participants 59 48 58 62
    Least Squares Mean (Standard Error) [score on a scale]
    -16.4
    (1.43)
    -12.2
    (1.57)
    -11.4
    (1.46)
    -10.5
    (1.40)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Brexpiprazole + Sertraline, Placebo
    Comments MMRM analysis with an unstructured (UN) variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value =0.0021
    Comments
    Method Mixed Model Repeated Measures (MMRM)
    Comments
    Method of Estimation Estimation Parameter Least Squares (LS ) Mean Difference
    Estimated Value -5.99
    Confidence Interval (2-Sided) 95%
    -9.79 to -2.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Brexpiprazole, Placebo
    Comments MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value =0.3868
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.74
    Confidence Interval (2-Sided) 95%
    -5.70 to 2.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sertraline, Placebo
    Comments MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value =0.6399
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.91
    Confidence Interval (2-Sided) 95%
    -4.74 to 2.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Brexpiprazole + Sertraline, Sertraline
    Comments MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value =0.0106
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -5.08
    Confidence Interval (2-Sided) 95%
    -8.96 to -1.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Brexpiprazole + Sertraline, Brexpiprazole
    Comments MMRM analysis with an UN variance covariance structure was performed. The model included fixed class-effect terms for treatment, trial site, type of trauma (combat related Yes/No), visit week, and an interaction term of treatment by visit week and included the interaction term of baseline values of CAPS-5 total score by visit week as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value =0.0384
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -4.24
    Confidence Interval (2-Sided) 95%
    -8.26 to -0.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame From the first dose of the study drug up to 14 days after the last dose (Up to Week 14)
    Adverse Event Reporting Description Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
    Arm/Group Title Brexpiprazole + Sertraline Brexpiprazole Sertraline Placebo
    Arm/Group Description Participants were administered oral brexpiprazole initial dose of 0.5 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. 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. 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. Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
    All Cause Mortality
    Brexpiprazole + Sertraline Brexpiprazole Sertraline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/80 (0%) 0/75 (0%) 0/79 (0%) 1/82 (1.2%)
    Serious Adverse Events
    Brexpiprazole + Sertraline Brexpiprazole Sertraline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/80 (2.5%) 1/75 (1.3%) 0/79 (0%) 4/82 (4.9%)
    General disorders
    Chest pain 0/80 (0%) 0/75 (0%) 0/79 (0%) 1/82 (1.2%)
    Hepatobiliary disorders
    Bile duct stone 0/80 (0%) 0/75 (0%) 0/79 (0%) 1/82 (1.2%)
    Injury, poisoning and procedural complications
    Animal bite 0/80 (0%) 1/75 (1.3%) 0/79 (0%) 0/82 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/80 (1.3%) 0/75 (0%) 0/79 (0%) 1/82 (1.2%)
    Osteonecrosis 0/80 (0%) 0/75 (0%) 0/79 (0%) 1/82 (1.2%)
    Psychiatric disorders
    Suicide attempt 1/80 (1.3%) 0/75 (0%) 0/79 (0%) 0/82 (0%)
    Other (Not Including Serious) Adverse Events
    Brexpiprazole + Sertraline Brexpiprazole Sertraline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 47/80 (58.8%) 42/75 (56%) 46/79 (58.2%) 43/82 (52.4%)
    Gastrointestinal disorders
    Constipation 4/80 (5%) 2/75 (2.7%) 4/79 (5.1%) 4/82 (4.9%)
    Diarrhoea 5/80 (6.3%) 3/75 (4%) 7/79 (8.9%) 5/82 (6.1%)
    Dry mouth 5/80 (6.3%) 6/75 (8%) 10/79 (12.7%) 7/82 (8.5%)
    Nausea 4/80 (5%) 1/75 (1.3%) 16/79 (20.3%) 4/82 (4.9%)
    Vomiting 1/80 (1.3%) 0/75 (0%) 4/79 (5.1%) 0/82 (0%)
    General disorders
    Fatigue 2/80 (2.5%) 6/75 (8%) 4/79 (5.1%) 0/82 (0%)
    Infections and infestations
    Upper respiratory tract infection 3/80 (3.8%) 7/75 (9.3%) 7/79 (8.9%) 7/82 (8.5%)
    Investigations
    Weight increase 10/80 (12.5%) 6/75 (8%) 1/79 (1.3%) 7/82 (8.5%)
    Metabolism and nutrition disorders
    Decreased appetite 6/80 (7.5%) 5/75 (6.7%) 1/79 (1.3%) 1/82 (1.2%)
    Nervous system disorders
    Akathisia 5/80 (6.3%) 10/75 (13.3%) 3/79 (3.8%) 2/82 (2.4%)
    Dizziness 2/80 (2.5%) 2/75 (2.7%) 5/79 (6.3%) 5/82 (6.1%)
    Headache 6/80 (7.5%) 4/75 (5.3%) 7/79 (8.9%) 7/82 (8.5%)
    Sedation 3/80 (3.8%) 5/75 (6.7%) 0/79 (0%) 0/82 (0%)
    Somnolence 8/80 (10%) 5/75 (6.7%) 3/79 (3.8%) 7/82 (8.5%)
    Psychiatric disorders
    Anorgasmia 4/80 (5%) 1/75 (1.3%) 1/79 (1.3%) 0/82 (0%)
    Anxiety 3/80 (3.8%) 4/75 (5.3%) 0/79 (0%) 4/82 (4.9%)
    Insomnia 2/80 (2.5%) 5/75 (6.7%) 4/79 (5.1%) 3/82 (3.7%)
    Irritability 3/80 (3.8%) 1/75 (1.3%) 4/79 (5.1%) 3/82 (3.7%)
    Reproductive system and breast disorders
    Delayed ejaculation 4/80 (5%) 0/75 (0%) 1/79 (1.3%) 0/82 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis Contact 4/80 (5%) 0/75 (0%) 1/79 (1.3%) 1/82 (1.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.

    Results Point of Contact

    Name/Title Global Clinical Development
    Organization Otsuka Pharmaceutical Development & Commercialization, Inc.
    Phone 1-609-524-6788
    Email clinicaltransparency@otsuka-us.com
    Responsible Party:
    Otsuka Pharmaceutical Development & Commercialization, Inc.
    ClinicalTrials.gov Identifier:
    NCT03033069
    Other Study ID Numbers:
    • 331-201-00061
    First Posted:
    Jan 26, 2017
    Last Update Posted:
    Dec 8, 2021
    Last Verified:
    Nov 1, 2021