Safety of BI 1358894 in patients with major depressive disorder: Results and learnings from a phase II randomized decentralized clinical trial

Abstract

The feasibility of conducting a fully remote, interventional, phase II decentralized clinical trial (DCT) was investigated in major depressive disorder (MDD). Key learnings were collated to improve future DCTs. A double-blind, placebo-controlled, parallel-group, DCT enrolled adult MDD patients with inadequate response to first-line antidepressant monotherapy (ongoing ≥8 weeks) and a Montgomery-Åsberg Depression Rating Scale total score (MADRS) ≥22 at screening. Patients were randomized 1:1 to BI 1358894 125 mg or placebo daily for 6 weeks remotely. Safety parameters, primary end point (change from baseline in MADRS at Week 6), and patient experience were assessed. The DCT was considered feasible if the trial protocol could be successfully executed. Overall, DCT procedures were successfully executed per protocol. However, despite achieving a vast patient outreach, the trial was terminated early due to deficient enrollment. Of the 136 patients who consented for enrollment and underwent screening, 45 were randomized and 43 received treatment (BI 1358894, n = 20; placebo, n = 23); 97.7% of patients completed the trial. Patients had a mean (SD) age of 42.2 (13.1) years and most (83.7%) were female. Adverse events were reported by 86.0% of patients (BI 1358894, 90.0%; placebo, 82.6%). Most patients (88%) reported a positive experience with the DCT. Key learnings related to the impact of stringent eligibility criteria, recruitment optimization strategies, plus the benefits and limitations of digital technologies. A fully remote, interventional DCT was feasible in MDD, and was well perceived by trial participants. Learnings related to recruitment optimization and trial design should be considered for future interventional DCTs.