Abstract

Introduction: Population exposure‑response analysis was undertaken to describe the relationship of drug concentrations to measures of clinical efficacy and safety in patients with schizophrenia or bipolar mania.

Methods: Data were obtained from >800 patients with bipolar mania who were randomized to cariprazine (3–12 mg/d) or placebo in two 3‑week, double‑blind, placebo‑controlled Phase 3 studies. Data were obtained from >1700 patients with
schizophrenia who were administered cariprazine (1.5–21 mg/d) or placebo in two Phase 1b and five Phase 2/3 studies
(3–6‑week, double‑blind, placebo‑controlled studies). Exposure metrics based on total cariprazine [nM] (defined as the molar sum of cariprazine and its two major metabolites of similar pharmacological activity, desmethyl‑cariprazine [DCAR] and didesmethyl‑cariprazine [DDCAR]) were explored for potential relationships with efficacy and safety endpoints. Modeling was performed with NONMEM, a nonlinear mixed‑effects modeling software package, utilizing standard pharmacometric techniques.

American Psychiatric Association (APA) Annual Meeting. May 14-18, 2016, Atlanta, GA.

By Timothy Carrothers, ScD, Susan Willavize, PhD, David Jaworowicz, PhD, Julie Passarell, MA, Antonia Periclou, PhD, Parviz Ghahramani, PhD, Suresh Durgam, MD, Willie Earley, MD, Margit Kapás, PhD, Tatiana Khariton, PhD