Intra-Cellular announces Study 404 of lumateperone met primary endpoint
Intra-Cellular Therapies announced top-line results from two Phase 3 clinical trials evaluating lumateperone as monotherapy in the treatment of major depressive episodes associated with Bipolar I or Bipolar II disorder. In Study 404, lumateperone 42 mg met the primary endpoint for improvement in depression as measured by change from baseline versus placebo on the MADRS total score. Study 404 also met its key secondary endpoint, Clinical Global Impression Scale for Bipolar for Severity of Illness Total Score. In both trials, lumateperone demonstrated a favorable safety profile and was generally well-tolerated. Study 404 was conducted globally including in the U.S. A total of 381 patients were randomized 1:1 to lumateperone 42 mg or placebo. In this trial, once-daily lumateperone 42 mg met the primary endpoint with statistically significant greater improvement over placebo at week 6 as measured by change from baseline on the MADRS total score. In the intent-to-treat study population, the least squares mean reduction from baseline for lumateperone 42 mg was 16.7 points, versus 12.1 points for placebo. Moreover, lumateperone 42 mg showed statistically significant separation from placebo as early as week 1, which was maintained at every time point throughout the trial. Lumateperone 42 mg also met the key secondary endpoint of statistically significant improvement on the CGI-BP-S Total Score and on the CGI component that specifically assesses depression. These results were supported by statistically significant benefits on responder rates and remission rates, demonstrating the clinical meaningfulness of the primary outcome. In addition, in subgroup analyses of patients with Bipolar I and patients with Bipolar II disorder lumateperone 42 mg demonstrated statistically significant improvement versus placebo on the MADRS total score in both subgroups. Study 401 was conducted solely in the U.S. A total of 554 patients were randomized 1:1:1 to lumateperone 42 mg, lumateperone 28 mg, or placebo. In this trial, neither dose of lumateperone met the primary endpoint of statistical separation from placebo as measured by change from baseline on the MADRS total score. There was a high placebo response in this trial. Lumateperone 42 mg and 28 mg demonstrated a LS mean reduction from baseline on the MADRS total score of 20.7 points and 18.9 points, respectively, versus 19.7 points on placebo. Consistent with previous studies in schizophrenia, lumateperone was well-tolerated in both bipolar depression studies, with a favorable safety profile. The rates of discontinuation due to treatment emergent adverse events for both doses of lumateperone were low. In Study 404, the most commonly reported adverse events that were observed at a rate greater than 5% and higher than placebo were headache, somnolence and nausea. In Study 401, the most commonly reported adverse events that were observed at rates greater than 5% and higher than placebo for either dose were somnolence, headache, nausea, dry mouth, dizziness, diarrhea, vomiting and fatigue. Importantly, the rates of akathisia, restlessness and extrapyramidal symptoms combined were less than 1% and similar to placebo in both studies. These findings are consistent with previous lumateperone trials in patients with schizophrenia and provide further evidence supporting lumateperone's favorable safety and tolerability profile across different patient populations.