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

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)

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.

Study Overview

• Status: Completed
• Conditions: Post-Traumatic Stress Disorder
• Intervention / Treatment: Drug: Placebo; Drug: BI 1358894

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 2

Contacts and Locations

Study Locations

• Croatia
  • Rijeka, Croatia, 51 000
    • Clincal Hospital Centre Rijeka
  • Zagreb, Croatia, 10000
    • Polyclinic Neuron
  • Zagreb, Croatia, 10090
    • University Psychiatric Hospital Vrapce
  • Zagreb, Croatia, 10090
    • Psychiatric Hospital 'Sveti Ivan'
  • Zagreb, Croatia, 10000
    • Solmed Polyclinic
• Finland
  • Helsinki, Finland, 00150
    • Eira Medical Centre
  • Oulu, Finland, 90100
    • Oulu Mentalcare Oy
  • Tampere, Finland, FI-33210
    • Mehiläinen Tampere
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen, AöR
  • Mannheim, Germany, 68159
    • Zentralinstitut für Seelische Gesundheit
  • München, Germany, 80336
    • Klinikum der Universität München - Campus Innenstadt
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
• Israel
  • Tel Hashomer, Israel, 52621
    • The Chaim Sheba Medical Center Tel HaShomer
• Mexico
  • Culiacan, Mexico, 80230
    • Centro Para El Desarrollo de La Medicina Y de Asistencia Medica Especializada S.C.
  • Leon, Mexico, 37000
    • Hospital Aranda de La Parra
  • Monterrey, Mexico, 64610
    • CIT-Neuropsique S.C
  • San Luis Potosi, Mexico, 78213
    • BIND Investigaciones S.C.
• Poland
  • Bialystok, Poland, 15-404
    • MlynowaMed
  • Bydgoszcz, Poland, 85-048
    • In-Vivo Sp. z o.o.
  • Warszawa, Poland, 02-172
    • MTZ Clinical Research Powered by Pratia
• Sweden
  • Enskede, Sweden, 122 31
    • Psykiatri Södra Stockholm
  • Gothenburg, Sweden, 416 50
    • Psykiatri Affektiva sjukdomar
  • Huddinge/Stockholm, Sweden, 141 86
    • Psykiatri Sydväst Stockholm
  • Uppsala, Sweden, 751 85
    • Akademiska Sjukhuset
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, Inc.
  • California
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • Long Beach, California, United States, 90807
      • ASCLEPES Research Centers, P.C. dba Alliance Research
    • Los Angeles, California, United States, 90025
      • CalNeuro Research Group Inc.
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research, LLC
    • Santa Ana, California, United States, 92705
      • Clinical Innovations Inc.
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research
    • Torrance, California, United States, 90504
      • Collaborative Neuroscience Research, LLC
  • Colorado
    • Denver, Colorado, United States, 80202
      • Mountain Mind. LLC
  • Florida
    • Coral Springs, Florida, United States, 33067
      • Cns Clinical Research - Coral Springs
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute, LLC
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Saint Petersburg, Florida, United States, 33713
      • Elixia PHC, LLC
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Institute for Advanced Medical Research
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • American Medical Research
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Incorporated
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Springfield, Massachusetts, United States, 01103
      • Sisu BHR, LLC
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • NeuroBehavioral Medicine Group
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
  • New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Insight Clinical Trials
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research, LLC
  • Texas
    • Austin, Texas, United States, 78712
      • The University of Texas at Austin
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials, LLC
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA
    • San Antonio, Texas, United States, 78229
      • Audie L. Murphy VA Hospital
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Virginia
    • Salem, Virginia, United States, 24153
      • Salem VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: BI 1358894 125 mg	Drug: BI 1358894; BI 1358894

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At baseline and at 8 weeks after start of treatment.
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.	At baseline and at 8 weeks after start of treatment.
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.	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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2021
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): November 2, 2021

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: 1402-0030; 2021-003154-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No