Trial Outcomes & Findings for A Home-based Study Using Mobile Technology to Test Whether BI 1358894 is Effective in People With Depression (NCT NCT04423757)

Last Updated: 2023-06-13

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

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.

Results posted on

2023-06-13

Participant Flow

This study was conducted as a decentralized clinical trial (DCT). It was a 6-week parallel-group, randomized, double-blinded, placebo-controlled Phase II trial in participants with Major Depressive Disorder (MDD) with inadequate response to ongoing treatment of an Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin and Norepinephrine Reuptake Inhibitor (SNRI).

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	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.	Placebo Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Overall Study STARTED	21	24
Overall Study Treated	20	23
Overall Study COMPLETED	18	23
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Placebo Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Overall Study Adverse Event	2	0
Overall Study Not treated	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 1358894 n=20 Participants 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.	Placebo n=23 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.	Total n=43 Participants Total of all reporting groups
Age, Continuous	41.1 years STANDARD_DEVIATION 13.4 • n=5 Participants	43.2 years STANDARD_DEVIATION 13.0 • n=7 Participants	42.2 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	21 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Montgomery-Åsberg Depression Rating Scale (MADRS)	26.6 Score on a scale STANDARD_DEVIATION 6.6 • n=5 Participants	28.4 Score on a scale STANDARD_DEVIATION 7.1 • n=7 Participants	27.6 Score on a scale STANDARD_DEVIATION 6.9 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BI 1358894 n=20 Participants 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.	Placebo n=23 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Change From Baseline in MADRS Total Score at Week 6	-9.98 Score on a scale Standard Error NA Adjusted standard error = 2.3	-13.36 Score on a scale Standard Error NA Adjusted standard error = 2.0

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	BI 1358894 n=20 Participants 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.	Placebo n=23 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Number of Subjects With ≥ 50% MADRS Reduction From Baseline at Week 6	6 Participants	14 Participants

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	BI 1358894 n=19 Participants 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.	Placebo n=23 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6 S-Anxiety scale	-9.10 Score on a scale Standard Error NA Adjusted standard error = 2.6	-10.45 Score on a scale Standard Error NA Adjusted standard error = 2.3
Change From Baseline in State-Trait Anxiety Inventory (STAI) Scores at Week 6 T-Anxiety scale	-8.70 Score on a scale Standard Error NA Adjusted standard error = 2.3	-12.24 Score on a scale Standard Error NA Adjusted standard error = 2.0

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	BI 1358894 n=20 Participants 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.	Placebo n=23 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6	-1.14 Score on a scale Standard Error NA Adjusted standard error = 0.3	-1.65 Score on a scale Standard Error NA Adjusted standard error = 0.3

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	BI 1358894 n=19 Participants 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.	Placebo n=23 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6	-13.56 Score on a scale Standard Error NA Adjusted standard error = 2.3	-14.21 Score on a scale Standard Error NA Adjusted standard error = 2.0

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	BI 1358894 n=11 Participants 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.	Placebo n=14 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Change From Baseline in Patient Global Impression Severity Scale (PGI-S) Score at Week 6	-0.37 Score on a scale Standard Error NA Adjusted standard error = 0.3	-0.60 Score on a scale Standard Error NA Adjusted standard error = 0.2

SECONDARY outcome

Timeframe: After 6 weeks of treatment.

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

Outcome measures

Outcome measures
Measure	BI 1358894 n=20 Participants 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.	Placebo n=23 Participants Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Patient Global Impression of Change Scale (PGI-C) Score at Week 6	2.8 Score on a scale Standard Deviation 1.1	2.8 Score on a scale Standard Deviation 1.7

Adverse Events

BI 1358894

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BI 1358894 n=20 participants at risk 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.	Placebo n=23 participants at risk Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
Psychiatric disorders Depression	0.00% 0/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	4.3% 1/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Psychiatric disorders Major depression	0.00% 0/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	4.3% 1/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.

Other adverse events

Additional Information

Boehringer Ingelheim , Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	BI 1358894 n=20 participants at risk 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.	Placebo n=23 participants at risk Placebo matching BI 1358894 taken orally as three film-coated tablets once a day in the morning for six weeks.
General disorders Feeling abnormal	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	0.00% 0/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
General disorders Pyrexia	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	0.00% 0/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Psychiatric disorders Insomnia	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	8.7% 2/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Injury, poisoning and procedural complications Contusion	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	13.0% 3/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Metabolism and nutrition disorders Decreased appetite	5.0% 1/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	8.7% 2/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Nervous system disorders Dizziness	25.0% 5/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	4.3% 1/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Nervous system disorders Headache	30.0% 6/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	13.0% 3/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Nervous system disorders Somnolence	5.0% 1/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	13.0% 3/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Gastrointestinal disorders Diarrhoea	5.0% 1/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	8.7% 2/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Gastrointestinal disorders Dry mouth	15.0% 3/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	4.3% 1/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Gastrointestinal disorders Nausea	15.0% 3/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	0.00% 0/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Gastrointestinal disorders Vomiting	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	0.00% 0/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
General disorders Fatigue	25.0% 5/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	8.7% 2/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	8.7% 2/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	4.3% 1/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.
Vascular disorders Hot flush	10.0% 2/20 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.	0.00% 0/23 • From the date of first treatment administration till the date of the last treatment administration + Residual effect period, up to 70 days. Treated Set (TS): all subjects who were randomized and received at least one administration of study drug.