Relationship Between Pimavanserin Exposure and QTc Interval in Patients with Schizophrenia: Modelling Analysis from Randomized, Double-Blind, Placebo-Controlled Studies

Authors: Darwish M, Bugarski-Kirola D, Passarell JA, Fellows Maxwell K, Owen JS, DeKarske D, Stankovic S
Conference: European College of Neuropsychopharmacology (ECNP) Congress
Keywords: 5-HT2A receptors, 5-HT2C receptors, ADVANCE, antipsychotic treatment, antipsychotics, ENHANCE, exposure-response, pimavanserin, QTc, schizophrenia
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

• Patients with schizophrenia who are receiving more than one antipsychotic may be at higher risk for QT interval prolongation.

• Pimavanserin, a serotonin receptor-modulating agent with inverse agonist/antagonist activity at 5-HT2A receptors and to a lesser extent 5-HT2C receptors, is being investigated for treatment of negative symptoms of schizophrenia.

• Pimavanserin prolongs the QT interval, with mean increases in corrected QT (QTc) interval of approximately 5–8 ms.

• Two studies, ADVANCE and ENHANCE, investigated the efficacy and safety of pimavanserin in patients with schizophrenia when added to background antipsychotic treatment. Exposure–response (ER) analyses of data collected in these studies can help assess the potential for effects on the QTc interval in patients with schizophrenia receiving repeated clinical doses of pimavanserin in the presence of background antipsychotics.

By, Mona Darwish, Dragana Bugarski-Kirola, Julie Passarell, Kelly Maxwell, Joel Owen, Daryl DeKarske, Srdjan Stankovic.

Poster presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress; October 2–5 2021; Virtual.