Chapel S (1), Chiu Y(2), Hsu J(2), Cucchiaro J(2), Loebel A(2)
(1) Ann Arbor Pharmacometrics Group, Inc (A2PG), Ann Arbor, MI (2) Sunovion Pharmaceuticals, Inc, Ft. Lee, NJ
Objectives: Characterization of dose- response relationships for psychotropic agents may be difficult to determine based on results of individual clinical trials, due to various confounds such as variability in attrition, background medications, flexible dosing designs, and placebo-response rates. The goal of this exposure-efficacy response analysis was to characterize dose-response effects for lurasidone and to predict efficacy at Week 6, based on the results of two recently completed placebo-controlled studies in patients with bipolar depression.
Methods: The exposure-efficacy response analyses were derived from two randomized, 6-week, double-blind, placebo-controlled, flexible-dose (20-120 mg in adjunctive Study D1050235; 20-60 or 80-120 mg in monotherapy Study D1050236) studies in subjects with bipolar depression. A total of 5245 Montgomery-Asberg Depression Rating Scale (MADRS) observations from 825 patients (who had received lurasidone or placebo treatments, with or without lithium or valproic acid background medication) were included in the analysis.
Results: The time profile of MADRS on placebo was adequately described using an exponential asymptotic model. MADRS vs. time profiles for either placebo or lurasidone were adequately described using a linear dose-response relationship built on an exponential asymptotic placebo model. A net improvement in MADRS due to lurasidone treatment (the drug effect) was significant (p<0.001) and a positive dose-response was detected. Covariate effects were significant only on placebo effect parameters, thus no dose adjustment is necessary based on demographic covariates. Age and use of concomitant medication had statistically significant covariate effects on placebo effect. Overall, the dose-dependent effect of lurasidone indicates that higher doses are likely to produce higher drug effect. The dose-response was consistent for both monotherapy and adjunctive therapy studies.
Conclusions: The effect of lurasidone was described using a linear dose-response model for drug effect, with increased treatment response in patients with bipolar depression observed at higher doses of lurasidone.
Reference: PAGE 22 () Abstr 2723 [www.page-meeting.org/?abstract=2723]
Poster: CNS