Stress Disorders, Post-Traumatic
Conditions
Brief summary
This study will evaluate the efficacy and safety of 10 mg of oral administration balovaptan once a day (QD) compared with matching placebo in adults with PTSD.
Interventions
DRUGBalovaptan
Intervention of oral administration of 10mg balovaptan QD for 12 weeks followed by two weeks of follow-up period
DRUGPlacebo
Matching placebo
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Participants who have a current diagnosis of PTSD as per DSM-5 criteria, with a score of \>/=33 on the PCL-5 at screening * The index trauma event must have occurred in adulthood, i.e., when the participant was \>/=18 years old * The index trauma event must have occurred at least 6 months prior to screening and no more than 10 years prior to screening * At baseline, either taking a stable dose of a single antidepressant (SSRI or SNRI) for management of PTSD and have been on that medication for \>/=6 weeks at that stable dosage and demonstrating residual symptoms of PTSD or prior demonstrated lack of tolerability or lack of efficacy and not taking an antidepressant medication at baseline for \>/=6 weeks * Treatment with permitted medications and/or non-pharmacological interventions at a stable dose for 6 weeks prior to screening * For women of childbearing potential: agreement to remain abstinent or use contraception
Exclusion criteria
* Participants who are experiencing ongoing exposure to traumatic events within 3 months of screening * Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 14 days after the final dose of study drug * Clinically significant psychiatric and/or neurological conditions, which may interfere with the assessment of safety or efficacy endpoints * Substance use disorders during last 12 months * Significant risk for suicidal behaviour * Epilepsy or seizure disorder considered not well controlled within the past 6 months or changes in anticonvulsive therapy within the last 6 months * Clinical diagnosis of peripheral neuropathy * Within the last 2 years, unstable or clinically significant cardiovascular disorders * Positive serology results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) 1 or 2 * Moderate or severe hepatic or renal impairment * History of coagulopathies, bleeding disorders, blood dyscrasias, hematological malignancies, myelosuppression (including iatrogenic) * Medical history of malignancy, if not considered cured * Participants who have received treatment with investigational therapy within 8 weeks prior to randomization * Known hypersensitivity to balovaptan, its components, or any of the excipients used in the formulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score | From Baseline up to Week 12 | The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) measures the severity of PTSD where smaller scores indicate less severe PTSD and higher scores suggest more severe PTSD. Possible scores for this 30 item version range from 0 to 120. Measured 3 times over 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | From Baseline up to Week 12 | The CGI-S reflects the rater's impression of the subject's current PTSD severity on a 6-point scale ranging from no symptoms (1) to very severe symptoms (6). |
| Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score | From Baseline up to Week 12 | PHQ-9 is a 9-item PRO used to assess severity of depression. Responses are rated based on frequency of symptoms on a 4-point Likert scale, ranging from 0 (not at all) to 3 (nearly every day). A total PHQ-9 total score ranging from 0 to 27 can be calculated by summing the nine items, of which a higher score corresponds to more severe depression. |
| Percentage of Participants With Adverse Events | From Baseline up to Week 12 | — |
Countries
United States
Participant flow
Pre-assignment details
More participants (29) were enrolled than initially planned (16)
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo | 16 |
| Balovaptan Intervention of oral administration of 10mg balovaptan QD for 12 weeks followed by two weeks of follow-up period | 13 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Balovaptan | Total |
|---|---|---|---|
| Age, Continuous | 36.6 Years STANDARD_DEVIATION 8.2 | 38.2 Years STANDARD_DEVIATION 13.8 | 37.3 Years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 10 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 13 |
| other Total, other adverse events | 7 / 16 | 9 / 13 |
| serious Total, serious adverse events | 0 / 16 | 0 / 13 |
Outcome results
Primary
Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) measures the severity of PTSD where smaller scores indicate less severe PTSD and higher scores suggest more severe PTSD. Possible scores for this 30 item version range from 0 to 120. Measured 3 times over 12 weeks.
Time frame: From Baseline up to Week 12
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score | Baseline | 35.5 Score on a Scale | Standard Deviation 9.3 |
| Placebo | Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score | Week 6 | -6.8 Score on a Scale | Standard Deviation 11.2 |
| Placebo | Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score | Week 12 | -15.6 Score on a Scale | Standard Deviation 10.6 |
| Balovaptan | Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score | Baseline | 33.8 Score on a Scale | Standard Deviation 7.8 |
| Balovaptan | Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score | Week 6 | -10.3 Score on a Scale | Standard Deviation 9.2 |
| Balovaptan | Change From Baseline in the Clinician-Administered PTSD Total Symptom Severity Score | Week 12 | -17.2 Score on a Scale | Standard Deviation 10.7 |
Secondary
Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score
PHQ-9 is a 9-item PRO used to assess severity of depression. Responses are rated based on frequency of symptoms on a 4-point Likert scale, ranging from 0 (not at all) to 3 (nearly every day). A total PHQ-9 total score ranging from 0 to 27 can be calculated by summing the nine items, of which a higher score corresponds to more severe depression.
Time frame: From Baseline up to Week 12
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score | Baseline | 15.2 Score on a Scale | Standard Deviation 4.8 |
| Placebo | Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score | Week 6 | -2.7 Score on a Scale | Standard Deviation 5.6 |
| Placebo | Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score | Week 12 | -6.0 Score on a Scale | Standard Deviation 5.1 |
| Balovaptan | Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score | Baseline | 12.2 Score on a Scale | Standard Deviation 5.1 |
| Balovaptan | Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score | Week 6 | -2.5 Score on a Scale | Standard Deviation 5.8 |
| Balovaptan | Change From Baseline at Week 12 in the Patient Health Questionnaire-9 (PHQ-9) Total Score | Week 12 | -3.5 Score on a Scale | Standard Deviation 5.2 |
Secondary
Percentage of Participants With Adverse Events
Time frame: From Baseline up to Week 12
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events | 7 Participants |
| Balovaptan | Percentage of Participants With Adverse Events | 9 Participants |
Secondary
Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score
The CGI-S reflects the rater's impression of the subject's current PTSD severity on a 6-point scale ranging from no symptoms (1) to very severe symptoms (6).
Time frame: From Baseline up to Week 12
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Mild | 3 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Severe | 3 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Very severe | 0 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Very mild | 0 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Mild | 1 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Moderate | 3 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Severe | 11 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Very severe | 0 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Very mild | 0 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Mild | 0 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Moderate | 4 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Severe | 8 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Very severe | 0 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 No Symptoms | 2 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Very mild | 0 Participants |
| Placebo | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Moderate | 5 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Very severe | 0 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Mild | 6 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Severe | 1 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Moderate | 5 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Severe | 1 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Very mild | 0 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Very severe | 0 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 No Symptoms | 0 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Very mild | 0 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Mild | 4 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Mild | 0 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Very severe | 0 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Moderate | 8 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 6 Moderate | 8 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Baseline Severe | 5 Participants |
| Balovaptan | Symptom Severity as Measured by Clinician-Global Impression of Severity (CGI-S) Scale Score | Week 12 Very mild | 1 Participants |