A Home-based Study Using Mobile Technology to Test Whether BI 1358894 is Effective in People With Depression

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Depressive Disorder, Major

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 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 #3. 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

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1358894<br>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. | Drug: BI 1358894<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks. | Drug: Placebo<br>* Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MADRS Total Score at Week 6 | 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With ≥ 50% MADRS Reduction From Baseline at Week 6 | 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). Reported are the number of subjects with ≥ 50% MADRS reduction from baseline at Weeks 6. Percent reduction from baseline was calculated as (score at baseline - score at week 6) / score at baseline * 100. | Baseline (week 0) and after 6 weeks of treatment. | 
| Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6 | The State-Trait Anxiety Inventory (STAI) comprises separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale consists of twenty statements that evaluate how respondents feel right now, at this moment. The T-Anxiety scale consists of twenty statements that assess how people generally feel. Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80. Higher scores indicate greater anxiety. 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; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. | 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 | The CGI-S rating scale measures the clinician's impression of the severity of illness exhibited, taking into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 (best) to 7 (worst). Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. MMRM with fixed effects of treatment, visit, treatment by visit interaction, baseline, and baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. | 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 Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6 | The SMDDS is a 16-item, patient-reported outcome (PRO) measure developed to capture the core symptoms of MDD. The SMDDS uses a recall of over the past 7 days and participants respond to each question using a rating scale between 0 (Not at all or Never) to 4 (Extremely or Always). In calculating the total score, two of the items (item 11 and 12) are first combined, with the highest score across the two items selected for use in the total score calculation. Total score is then calculated by the sum of the individual 15 items, the total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology. 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; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. | 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 | The PGI-S was used to measure the patient's impression of the severity of their illness. It is a single item 4-point scale that asks patients to rate the severity of their illness. The PGI-S question states Please choose the response below that best describes the overall severity of your depression symptoms over the past week. None Mild Moderate Severe 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; unstructured covariance matrix for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. | 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 | The PGI-C is a one-time assessment at the end of treatment (EoT) to measure the patient's impression of the how their illness has changed over time. It is a single item 7-item scale that asks patients to rate the overall change since the start of treatment. The PGI-C question states Please choose the response below that best describes the overall change in your depression symptoms since you started taking the study medication. Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse | After 6 weeks of treatment. |