Post-traumatic Stress Disorder, PTSD
Conditions
Brief summary
To evaluate the efficacy of brexpiprazole as adjunctive treatment to paroxetine (PAR) or sertraline (SER) on PTSD symptoms.
Interventions
DRUGPlacebo
Once daily, tablets, orally
DRUGBrexpiprazole
1 to 3 mg/day, once daily dose, tablets, orally
Sponsors
Otsuka Pharmaceutical Co., Ltd.
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The patient has PTSD, diagnosed according to DSM-IV-TR™ and confirmed by the Mini International Neuropsychiatric Interview (MINI). * The patient has a Clinician-Administered PTSD Scale Part 2 (CAPS-2) total score ≥70 at Screening and Baseline Visits. * The reported duration of the PTSD is at least 3 months.
Exclusion criteria
* The index traumatic event that led to development of PTSD took place more than 15 years before screening. * The patient has a severe personality disorder that in the investigator's opinion may interfere with the conduct of the study. * The patient is at significant suicidal risk. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PTSD Symptoms Using CAPS-2 Total Score | Period 2: Baseline to Week 12 (of randomized period) | Clinician-Administered PTSD Scale Part 2 (CAPS-2): 17 items in criteria B, C and D (Corresponding to CAPS-2) will be administered to provide a total score. They are rated on a 5 point scale for frequency from 0 (never or none) to 4 (daily or almost every day), and intensity from 0 (none) to 4 (extreme). The sum of the 17 items gives a toal score ranging from 0 to 136, with a higher score indicating greater symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global Clinical Impression Severity of Illness (CGI-S) Score | Period 2: Baseline to Week 12 (of randomized period) | Clinical Global Impression - Severity of Illness (CGI-S) The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). |
Countries
Estonia, Finland, France, Italy, Poland, Serbia, South Africa, Sweden, United States
Participant flow
Recruitment details
417 patients were enrolled to the study and 413 patients received open-label treatment with a commercially available treatment for PTSD (PAR/SER) in Period 1. Only 40 patients were randomized to Period 2, the randomized period, before the study was terminated; 190 patients entered Period 3. Data are only reported for the randomized period.
Participants by arm
| Arm | Count |
|---|---|
| Period 2 Placebo and PAR/SER (Randomized Period) Randomized placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER); randomized period.
Placebo: Once daily, tablets, orally | 17 |
| Period 2 Brexpiprazole and PAR/SER (Randomized Period) Randomized brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day; randomized period.
Brexpiprazole: 1 to 3 mg/day, once daily dose, tablets, orally | 23 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | administrative or other reason | 75 | 0 | 0 | 0 |
| Period 1 | Adverse Event | 24 | 0 | 0 | 0 |
| Period 1 | Lack of Efficacy | 4 | 0 | 0 | 0 |
| Period 1 | Lost to Follow-up | 40 | 0 | 0 | 0 |
| Period 1 | Non-compliance with IMP | 6 | 0 | 0 | 0 |
| Period 1 | Protocol Violation | 12 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 21 | 0 | 0 | 0 |
| Period 1 | Withdrawal of consent before treatment | 4 | 0 | 0 | 0 |
| Period 2 | Administrative or other reason | 0 | 5 | 7 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 1 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Period 3 | Administrative or other reason | 0 | 0 | 0 | 43 |
| Period 3 | Adverse Event | 0 | 0 | 0 | 7 |
| Period 3 | Lost to Follow-up | 0 | 0 | 0 | 5 |
| Period 3 | Non-compliance with IMP | 0 | 0 | 0 | 1 |
| Period 3 | Protocol Violation | 0 | 0 | 0 | 6 |
| Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 9 |
Baseline characteristics
| Characteristic | Period 2 Placebo and PAR/SER (Randomized Period) | Period 2 Brexpiprazole and PAR/SER (Randomized Period) | Total |
|---|---|---|---|
| Age, Continuous | 42.9 years STANDARD_DEVIATION 11.8 | 47.6 years STANDARD_DEVIATION 10.4 | 45.6 years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 23 | 8 / 17 |
| serious Total, serious adverse events | 0 / 23 | 0 / 17 |
Outcome results
Primary
PTSD Symptoms Using CAPS-2 Total Score
Clinician-Administered PTSD Scale Part 2 (CAPS-2): 17 items in criteria B, C and D (Corresponding to CAPS-2) will be administered to provide a total score. They are rated on a 5 point scale for frequency from 0 (never or none) to 4 (daily or almost every day), and intensity from 0 (none) to 4 (extreme). The sum of the 17 items gives a toal score ranging from 0 to 136, with a higher score indicating greater symptom severity.
Time frame: Period 2: Baseline to Week 12 (of randomized period)
Population: Due to the low number of enrolled patients eligible for randomization and the sponsor's early termination of the study, the data presented are descriptive i.e. the primary and key secondary efficacy analyses were not done
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period 2 Absolute Mean at Baseline; Placebo and PAR/SER | PTSD Symptoms Using CAPS-2 Total Score | 82.82 Score | Standard Deviation 12.94 |
| Period 2 Absolute Mean at Baseline; Brexpiprazole and PAR/SER | PTSD Symptoms Using CAPS-2 Total Score | 83.43 Score | Standard Deviation 13.12 |
| Period 2 Absolute Mean at Week 12; Placebo and PAR/SER | PTSD Symptoms Using CAPS-2 Total Score | 69.67 Score | Standard Deviation 20.26 |
| Period 2 Absolute Mean at Week 12; Brexpiprazole and PAR/SER | PTSD Symptoms Using CAPS-2 Total Score | 69.18 Score | Standard Deviation 18.17 |
Secondary
Global Clinical Impression Severity of Illness (CGI-S) Score
Clinical Global Impression - Severity of Illness (CGI-S) The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients).
Time frame: Period 2: Baseline to Week 12 (of randomized period)
Population: Due to the low number of enrolled patients eligible for randomization and the sponsor's early termination of the study, the data presented are descriptive i.e. the primary and key secondary efficacy analyses were not done.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period 2 Absolute Mean at Baseline; Placebo and PAR/SER | Global Clinical Impression Severity of Illness (CGI-S) Score | 4.24 Score | Standard Deviation 0.83 |
| Period 2 Absolute Mean at Baseline; Brexpiprazole and PAR/SER | Global Clinical Impression Severity of Illness (CGI-S) Score | 4.54 Score | Standard Deviation 0.73 |
| Period 2 Absolute Mean at Week 12; Placebo and PAR/SER | Global Clinical Impression Severity of Illness (CGI-S) Score | 3.73 Score | Standard Deviation 1.1 |
| Period 2 Absolute Mean at Week 12; Brexpiprazole and PAR/SER | Global Clinical Impression Severity of Illness (CGI-S) Score | 3.94 Score | Standard Deviation 0.83 |