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

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.

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.

Population: Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.

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.

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.

Population: Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.

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. 1. None 2. Mild 3. Moderate 4. 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.

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.

Population: Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.

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.

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.

Population: Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint. One subject in the BI 1358894 arm missed the baseline assessment for STAI and was excluded from this endpoint.

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.

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.

Population: Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.

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.

Time frame: Baseline (week 0) and after 6 weeks of treatment.

Population: Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.

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. 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse

Time frame: After 6 weeks of treatment.

Population: Full Analysis Set (FAS): all subjects who were randomized and received at least one administration of study drug that have a baseline and at least one evaluable post-baseline on-treatment measurement for the primary endpoint.