Purpose/background: Pimavanserin is a selective serotonin 5-HT2A receptor inverse agonist/antagonist being investigated in patients with negative symptoms of schizophrenia. This analysis aimed to characterize exposure-response relationships of pimavanserin in this population.

Methods/procedures: Exposure-response models were developed using data from ADVANCE. Patients with negative symptoms of schizophrenia receiving background antipsychotics were randomized to pimavanserin 20 mg (adjusted to 34 or 10 mg between weeks 2-8 based on efficacy or tolerability) or placebo for 26 weeks. Time-varying pimavanserin exposure measures were predicted for each patient using a population pharmacokinetic model and individual empiric Bayesian parameter estimates. Response measures were the Negative Symptom Assessment 16 (NSA-16, primary end point), Personal and Social Performance scale, negative symptoms component of the Clinical Global Impression of Schizophrenia-Severity Scale, and adverse events.

By, Mona Darwish, Dragana Bugarski-Kirola, Julie Passarell, Joel Owen, David Jaworowicz, Daryl DeKarske, and Srdjan Stankovic