Impact of Lumateperone compared to Quetiapine on MADRS in Indian patients with Bipolar II depression: A post-hoc analysis of a Phase 3 study

Introduction Lumateperone, an atypical antipsychotic drug, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors. Objectives This post-hoc analysis of an Indian Phase 3 study was conducted to evaluate the impact of Lumateperone 42mg compared to Quetiapine 300mg on severity of depression assessed via MADRS in patients with Bipolar II depression. Methods The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. This post-hoc analysis evaluated MADRS total score and individual items from Question 1 to Question 10 i.e. (Q1) Apparent sadness; (Q2) Reported sadness; (Q3) Inner tension; (Q4) Reduced sleep; (Q5) Reduced appetite; (Q6) Concentration difficulties; (Q7) Lassitude; (Q8) Inability to feel; (Q9) Pessimistic thoughts; and (Q10) Suicidal thoughts respectively and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583] Results This subgroup analysis included 462 patients, out of which 231 were in the Test group and 231 in the comparator group. The baseline demographic characteristics were comparable in between treatment arms. The reduction in MADRS score (total and individual items) from baseline to Day 42 in Test arm was comparable to Comparator arm [Figure 1 & 2]. The incidence of TEAEs were similar in both treatment arms [Test: 34.6%; Comparator: 35.5%] and no serious adverse events were reported. Image 1: Image 2: Conclusions This post-hoc analysis demonstrated that Lumateperone 42mg is comparable to Quetiapine 300mg in treatment of Bipolar II depression as assessed via MADRS score from baseline to Day 42, and both treatments were found to be well tolerated. Hence, Lumateperone can be considered as valuable treatment option in management of Bipolar II depression. Disclosure of Interest A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma.