A Phase II 6-week, Randomized, Double-blinded, Placebo Controlled, Parallel Group Decentralised Clinical Trial to Evaluate Efficacy and Safety of Oral BI 1358894 in Patients With Major Depressive Disorder With Inadequate Response to Antidepressants
Overview
- Phase
- Phase 2
- Intervention
- BI 1358894
- Conditions
- Depressive Disorder, Major
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Change From Baseline in MADRS Total Score at Week 6
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a home-based study in adults with depression. People who have been diagnosed with Major Depressive Disorder can participate in the study. Participants can take part if they are being treated for their depression but still have symptoms. The purpose of this study is to find out whether a medicine called BI 1358894 helps people with depression.
Participants are in the study for about 2 months and do not need to visit a study site during this time. All study visits are conducted at participant's home by a mobile study nurse, by videoconference, and by phone calls. Participants are put into 2 groups by chance. One group takes BI 1358894 tablets. The other group takes placebo tablets. Placebo tablets look like BI 1358894 tablets but do not contain any medicine.
The participants answer questions about the symptoms of their depression. We then compare the results between the BI 1358894 and placebo groups. The doctors and nurses also regularly check the general health of the participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Established diagnosis of Major Depressive Disorder, single episode or recurrent, as confirmed at the time of screening by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders v5 (DSM-5, SCID-5), with a duration of current depressive episode ≥ 8 weeks and ≤ 12 months at the time of screening visit.
- •Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 22 at screening, as confirmed by a trained rater. In addition, trial participants must have a score of ≥ 3 on the Reported Sadness item on MADRS.
- •A documented ongoing monotherapy treatment of ≥ 8 weeks at the screening visit, with a protocol specified SSRI or SNRI (refer to the ISF) at adequate dose (at least minimum effective dose as per prescribing information and as confirmed per detectable drug levels in the screening blood or urine sampling).
- •Male and female participants, 18 to 65 years of age, both inclusively at the time of consent.
- •Women of child-bearing potential (WOCBP)2 able and willing to use two methods of contraception, which include one highly effective method of birth control per ICH M3 (R2) that results in a low failure rate of less than 1%, plus one barrier method.
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
- •Able to communicate well, and to understand and comply with trial requirements.
Exclusion Criteria
- •Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, delusional disorder or MDD with psychotic features as assessed by the Structured Clinical Interview for DSM -5 (SCID-5) at the time of screening.
- •Diagnosis of any other mental disorder (in addition to those as described in Exclusion Criterion #1) that was the primary focus of treatment within 6 months prior to screening or at baseline (as per clinical discretion of the investigator).
- •Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder as per DSM-5 criteria, at the time of screening visit. Any other personality disorder at screening visit that significantly affects current psychiatric status and likely to impact trial participation, as per the judgement of investigator.
- •Diagnosis of a substance related disorder within 3 months prior to screening visit (with exception of caffeine and tobacco).
- •History of seizure disorders, stroke, brain tumor or any other major neurological illness that can impact participation in the trial.
- •History of 4 or more unsuccessful monotherapy treatments (at adequate dosage and duration, per local prescribing information of the product) with an approved antidepressant medication for the current ongoing major depressive episode. These include ongoing monotherapy treatment with a protocol specified SSRI or SNRI as described in Inclusion Criterion #
- •Any suicidal behavior in the past 12 months prior to screening (per investigator judgement including an actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour).
- •Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months prior to screening or at screening or baseline visit (i.e. active suicidal thought with method and intent but without specific plan, or active suicidal thought with method, intent and plan).
- •Further exclusion criteria apply
Arms & Interventions
BI 1358894
125 milligram (mg) BI 1358894 taken orally as three film-coated tablets (1x 25mg and 2x 50mg) once a day in the morning for six weeks.
Intervention: BI 1358894
Placebo
Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in MADRS Total Score at Week 6
Time Frame: Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.
The Montgomery-Åsberg Depression Rating Scale (MADRS) evaluates core symptoms of depression. Nine of the items are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). Total score is calculated by the sum of the individual items, the possible total score could range from 0 to 60 (0= normal with absence of symptoms, 60=severe depression). The adjusted mean (SE) are based on a mixed effects model for repeated measures (MMRM) with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect.
Secondary Outcomes
- Number of Subjects With ≥ 50% MADRS Reduction From Baseline at Week 6(Baseline (week 0) and after 6 weeks of treatment.)
- Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6(Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.)
- Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6(Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.)
- Change From Baseline in Patient Global Impression Severity Scale (PGI-S) Score at Week 6(Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.)
- Patient Global Impression of Change Scale (PGI-C) Score at Week 6(After 6 weeks of treatment.)
- Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6(Week 0 (baseline) and after 1, 2, 4 and 6 week(s) of treatment. Change from baseline at week 6 MMRM estimates are reported in the table below.)