A Study to Test Whether Taking BI 1358894 for 8 Weeks Helps Adults With Post-traumatic Stress Disorder

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, 8-week-treatment, Multicenter, Randomized, Doubleblind, Placebo-controlled, Parallel Group Trial to Evaluate the Efficacy, Tolerability and Safety of Orally Administered BI 1358894 in Patients With Post-Traumatic Stress Disorder (PTSD)

Conditions
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Post-Traumatic Stress Disorder

Intervention / Treatment
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* Drug: BI 1358894
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Corresponding to DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, delusional disorder, brief psychotic disorder or any other psychotic disorder as well as Major Depressive Disorder (MDD) with psychotic features as assessed by the Mini-International Neuropsychiatric Interview (MINI) at the time of screening Any psychiatric or non-psychiatric medical condition likely to negatively impact trial participation as per the judgement of the investigator Acute stress disorder or significant traumatic event within 3 months prior to the screening visit Use of stimulant medications within 3 months prior to the screening visit (Attention Deficit Hyperactivity Disorder (ADHD) diagnosis alone is not exclusionary) Severe traumatic brain injury (life-time) or moderate traumatic brain injury within the last 2 years prior to screening visit or 3 months for mild traumatic brain injury, based on the Ohio State University Traumatic Brain Injury (TBI) Identification Method Short Form. Or history of traumatic brain injury that would impact ability to complete trial assessments or procedures according to investigator. Current treatment with trauma focused therapy (i.e. Cognitive Processing Therapy (CPT), Prolonged Exposure Therapy (PE), Eye Movement Desensitization and Reprocessing (EMDR)). A psychotherapy in type, intensity and/or frequency other than trauma focused therapy is allowed if stable within the last 8 weeks prior to screening and not anticipated to change during the entire course of the trial. Long-term psychotherapy is permitted as long as patients are not in an exposure phase during the trial. Diagnosis of a current moderate or severe alcohol use disorder according to MINI within 3 months prior to screening visit (mild alcohol use disorder (AUD) and patients in early remission = criterion not met for between 3 & 12 months are allowed) Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1358894<br> | Drug: BI 1358894<br>* BI 1358894<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Clinician-Administered Post-Traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) total severity score | CAPS-5 is a 30-item structured interview. In addition to assessing the 20 DSM-5 PTSD symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype (depersonalization and derealization). Each of the 20 symptom items is rated on a 5-point severity rating scale ranging from 0 (absent) to 4 (extreme/incapacitating) CAPS-5 total symptom severity score is yield by summing individual item scores. The total severity score ranges from 0 to 80 with higher scores indicating higher symptom severity. | At baseline and at week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Response defined as ≥30% CAPS-5 reduction from baseline | CAPS-5 is a 30-item structured interview. In addition to assessing the 20 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Post-Traumatic Stress Disorder (PTSD) symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype (depersonalization and derealization). Each of the 20 symptom items is rated on a 5-point severity rating scale ranging from 0 (absent) to 4 (extreme/incapacitating) CAPS-5 total symptom severity score is yield by summing individual item scores. The total severity score ranges from 0 to 80 with higher scores indicating higher symptom severity. | At baseline and at week 8 | 
| Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Response defined as ≥50% CAPS-5 reduction from baseline | CAPS-5 is a 30-item structured interview. In addition to assessing the 20 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Post-Traumatic Stress Disorder (PTSD) symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype (depersonalization and derealization). Each of the 20 symptom items is rated on a 5-point severity rating scale ranging from 0 (absent) to 4 (extreme/incapacitating) CAPS-5 total symptom severity score is yield by summing individual item scores. The total severity score ranges from 0 to 80 with higher scores indicating higher symptom severity. | At baseline and at week 8 | 
| Change from baseline on the PTSD Checklist for DSM-5 (PCL-5) total score | The PTSD Checklist for DSM-5 (PCL-5) is a 20-item patient-reported assessment designed to measure the presence and severity of PTSD symptoms. The PCL-5 is intended to assess patient symptoms in the past month. Each item is rated on a fivepoint Likert scale, from 0 (not at all) to 4 (extremely). A total severity score can be yield by summing up individual item scores, and ranges from 0 to 80 with higher scores indicating higher severity. | At baseline and at week 8 |