Trial Outcomes & Findings for A Study to Test Different Doses of BI 1569912 in People With Depression Who Take Anti-depressive Medicine (NCT NCT06280235)

A Phase II dose-finding trial to examine the efficacy and safety of oral BI 1569912 once daily over a 6-week treatment period in adult patients with moderate-to-severe major depressive disorder (MDD) who failed to respond to 1 or more antidepressants of adequate dose and duration in the current episode and who were still on stable treatment with current selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI).

All patients were screened for eligibility prior to participation in the trial, to ensure that they met all inclusion and none of the exclusion criteria. Patients who met all other eligibility criteria but were not on an SSRI/SNRI at Visit 1, had the option to undergo a 6-week open label lead-in phase with SSRI/SNRI. These patients were reassessed at Visit 1A to determine eligibility to be randomized to the trial.

The primary analysis set (PAS) comprises all randomised participants who received at least one dose of IMP during the trial and had a baseline MADRS total score ≥24.

Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). The Least Squares Mean (95 % confidence interval) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML-based MMRM) which includes the fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase), and fixed continuous effects of baseline MADRS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

Montgomery-Åsberg Depression Rating Scale (MADRS)s a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items, and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). The Least Squares Mean (95 % confidence intervals) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML-based MMRM) which includes the fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase), and fixed continuous effects of baseline MADRS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items, and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). Percentage of participants with a \>=50% reduction of the MADRS from baseline at Day 8 is reported. Percentages are rounded to one decimal place.

Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). Percentage of participants with a \>=50% reduction of the MADRS from baseline at Week 6 is reported. Percentages are rounded to one decimal place.

Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items, and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). Percentage of participants with a MADRS total score \<=10 at Week 6 is reported. Percentages are rounded to one decimal place.

SMDDS is a 16-item patient-reported measure where each item is rated from 0 ("Not at all/Never") to 4 ("Extremely/Always"). Total score ranges from 0-60, with higher scores indicating greater depression severity. Items 11 and 12 are combined by taking the higher score, then summed with the other 14 items. Least Squares Mean (95 % confidence interval) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML- based MMRM) with fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase) and baseline MADRS total score (\</\>=24), and fixed continuous effects of baseline SMDDS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

The SMDDS is a 16-item patient-reported measure where each item is rated from 0 ("Not at all/Never") to 4 ("Extremely/Always"). Total score ranges from 0-60, with higher scores indicating greater depression severity. Items 11 and 12 are combined by taking the higher score, then summed with the other 14 items. Least Squares Mean (95 % confidence interval) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML- based MMRM) with fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase) and baseline MADRS total score (\</\>=24), and fixed continuous effects of baseline SMDDS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.