Post-Traumatic Stress Disorder
Conditions
Brief summary
This study is open to people aged 18 to 65 who have post-traumatic stress disorder. The purpose of this study is to find out whether a medicine called BI 1358894 improves symptoms in people with post-traumatic stress disorder. Participants are put into 2 groups randomly, which means by chance. Participants take BI 1358894 or placebo as tablets every day for 2 months. Placebo tablets look like BI 1358894 tablets but do not contain any medicine. Participants are in the study for about 3 months. During this time, they visit the study site about 8 times and get about 4 phone calls from the trial staff. During the study, participants answer questions in interviews and complete questionnaires so the doctors can check whether their symptoms change. The doctors also regularly check participants' health and take note of any unwanted effects.
Interventions
DRUGBI 1358894
BI 1358894
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Established diagnosis of Post-Traumatic Stress Disorder (PTSD) corresponding to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria * Time since index event according to Life Events Checklist / Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Criterion A at least 3 months before screening visit * PTSD must be the clinically pre-dominant disorder, as per investigator´s judgement. Other comorbid psychiatric disorders are allowed, unless specifically excluded in the
Exclusion criteria
* A total severity score of ≥ 33 on the PTSD Checklist for DSM-5 (PCL-5) at the screening visit * Moderate to severe PTSD confirmed by CAPS-5 range ≥ 30 confirmed at screening visit * Male or female patients, 18 to 65 years of age, both inclusively at the time of informed consent * Women who are of child-bearing potential (WOCBP) must be able and willing to use two methods of contraception, as confirmed by the investigator, which include one highly effective method of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1%, plus one additional barrier method * Signed and dated written informed consent in accordance with International Council on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinician-Administered Post Traumatic Stress Disorder (PTSD) Scale for DSM-5 (CAPS-5) Total Severity Score at Week 8 | The MMRM model is a longitudinal analysis and it incorporated CAPS-5 measurements from baseline, Week 4, and Week 8. MMRM estimates of change from baseline to Week 8 is reported. | CAPS-5 is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Least Squares (LS) means and confidence intervals were estimated by restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAPS-5 Response, Defined as ≥30% CAPS-5 Reduction From Baseline at Week 8 | At baseline and at 8 weeks after start of treatment. | Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Number of participants with ≥30% CAPS-5 reduction from baseline at Week 8 is reported. |
| CAPS-5 Response, Defined as ≥50% CAPS-5 Reduction From Baseline at Week 8 | At baseline and at 8 weeks after start of treatment. | Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Number of participants with ≥50% CAPS-5 reduction from baseline at Week 8 is reported. |
| Change From Baseline on the PTSD Checklist for DSM-5 (PCL-5) Total Score at Week 8 | The MMRM model is a longitudinal analysis and it incorporated PCL-5 measurements from baseline, Week 4, and Week 8. MMRM estimates of change from baseline to Week 8 is reported. | The PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5) is a 20-item patient-reported assessment designed to measure the presence and severity of PTSD symptoms in the past month. Items on the PCL-5 correspond with DSM-5 criteria for PTSD. Each item is rated on a five point Likert scale, from 0 (not at all) to 4 (extremely) yielding a total score from 0-80 with higher scores indicating higher severity of the symptoms. Least Square (LS) means and confidence intervals were estimated by restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used. |
Countries
Croatia, Finland, Germany, Israel, Mexico, Poland, Sweden, United States
Participant flow
Recruitment details
This was a Phase II, 8-week-treatment, multicentre, randomised, double blind, placebocontrolled, parallel-group trial in patients with Post-Traumatic Stress Disorder (PTSD).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time. | 159 |
| BI 1358894 125 mg Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time. | 157 |
| Total | 316 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 14 |
| Overall Study | Burden of study procedures | 3 | 1 |
| Overall Study | No reason available | 5 | 4 |
| Overall Study | Not Treated | 1 | 1 |
| Overall Study | Other reasons than listed | 9 | 8 |
| Overall Study | Perceived lack of efficacy | 1 | 1 |
| Overall Study | Protocol deviation | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | BI 1358894 125 mg | Total |
|---|---|---|---|
| Age, Continuous | 44.0 Years STANDARD_DEVIATION 12.9 | 42.8 Years STANDARD_DEVIATION 12.4 | 43.4 Years STANDARD_DEVIATION 12.6 |
| CAPS-5 total severity score at baseline | 41.3 score on a scale STANDARD_DEVIATION 9.9 | 42.0 score on a scale STANDARD_DEVIATION 9.6 | 41.6 score on a scale STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 35 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 130 Participants | 122 Participants | 252 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 10 Participants | 16 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 46 Participants | 26 Participants | 72 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 102 Participants | 119 Participants | 221 Participants |
| Sex: Female, Male Female | 101 Participants | 111 Participants | 212 Participants |
| Sex: Female, Male Male | 58 Participants | 46 Participants | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 159 | 0 / 157 |
| other Total, other adverse events | 38 / 159 | 56 / 157 |
| serious Total, serious adverse events | 10 / 159 | 12 / 157 |
Outcome results
Primary
Change From Baseline in Clinician-Administered Post Traumatic Stress Disorder (PTSD) Scale for DSM-5 (CAPS-5) Total Severity Score at Week 8
CAPS-5 is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Least Squares (LS) means and confidence intervals were estimated by restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used.
Time frame: The MMRM model is a longitudinal analysis and it incorporated CAPS-5 measurements from baseline, Week 4, and Week 8. MMRM estimates of change from baseline to Week 8 is reported.
Population: Full analysis set (FAS): consisted of all patients in the treated set (TS) that had a baseline and at least one evaluable post-baseline measurement for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Clinician-Administered Post Traumatic Stress Disorder (PTSD) Scale for DSM-5 (CAPS-5) Total Severity Score at Week 8 | -17.19 units on a scale |
| BI 1358894 125 mg | Change From Baseline in Clinician-Administered Post Traumatic Stress Disorder (PTSD) Scale for DSM-5 (CAPS-5) Total Severity Score at Week 8 | -17.13 units on a scale |
Comparison: Least Squares (LS) means differences and confidence intervals were estimated by REML-based MMRM including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used.p-value: 0.972695% CI: [-3.31, 3.43]Mixed Models for repeated measures
Secondary
CAPS-5 Response, Defined as ≥30% CAPS-5 Reduction From Baseline at Week 8
Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Number of participants with ≥30% CAPS-5 reduction from baseline at Week 8 is reported.
Time frame: At baseline and at 8 weeks after start of treatment.
Population: Full analysis set (FAS): consisted of all patients in the treated set (TS) that had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Only participants with data from baseline and from Week 8 were included in the analysis of this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | CAPS-5 Response, Defined as ≥30% CAPS-5 Reduction From Baseline at Week 8 | 77 Participants |
| BI 1358894 125 mg | CAPS-5 Response, Defined as ≥30% CAPS-5 Reduction From Baseline at Week 8 | 77 Participants |
Comparison: Logistic regression was adjusted for fixed factors of treatment and presence of significant childhood trauma (yes vs. no).p-value: 0.994595% CI: [0.608, 1.65]Regression, Logistic
Secondary
CAPS-5 Response, Defined as ≥50% CAPS-5 Reduction From Baseline at Week 8
Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Number of participants with ≥50% CAPS-5 reduction from baseline at Week 8 is reported.
Time frame: At baseline and at 8 weeks after start of treatment.
Population: Full analysis set (FAS): consisted of all patients in the treated set (TS) that had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Only participants with data from baseline and from Week 8 were included in the analysis of this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | CAPS-5 Response, Defined as ≥50% CAPS-5 Reduction From Baseline at Week 8 | 53 Participants |
| BI 1358894 125 mg | CAPS-5 Response, Defined as ≥50% CAPS-5 Reduction From Baseline at Week 8 | 50 Participants |
Comparison: Logistic regression was adjusted for fixed factors of treatment and presence of significant childhood trauma (yes vs. no).p-value: 0.716795% CI: [0.552, 1.504]Regression, Logistic
Secondary
Change From Baseline on the PTSD Checklist for DSM-5 (PCL-5) Total Score at Week 8
The PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5) is a 20-item patient-reported assessment designed to measure the presence and severity of PTSD symptoms in the past month. Items on the PCL-5 correspond with DSM-5 criteria for PTSD. Each item is rated on a five point Likert scale, from 0 (not at all) to 4 (extremely) yielding a total score from 0-80 with higher scores indicating higher severity of the symptoms. Least Square (LS) means and confidence intervals were estimated by restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used.
Time frame: The MMRM model is a longitudinal analysis and it incorporated PCL-5 measurements from baseline, Week 4, and Week 8. MMRM estimates of change from baseline to Week 8 is reported.
Population: Full analysis set (FAS): consisted of all patients in the TS that had a baseline and at least one evaluable post-baseline measurement for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline on the PTSD Checklist for DSM-5 (PCL-5) Total Score at Week 8 | -19.21 units on a scale |
| BI 1358894 125 mg | Change From Baseline on the PTSD Checklist for DSM-5 (PCL-5) Total Score at Week 8 | -18.55 units on a scale |
Comparison: Least Square (LS) means differences and confidence intervals were estimated by REML-based MMRM including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used.p-value: 0.72395% CI: [-3, 4.32]Mixed Models for Repeated Measures