Exposure Response Modeling from the CLARITY Trail of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder

Authors: Darwish M, Dirks B, Passarell JA, Jaworowicz DJ, Bihorel S, Howell B, Owen JS, Stankovic S
Conference: SLP MIDD+
Keywords: CLARITY Trial, Depressive Disorder, Phase II, selective serotonin reuptake inhibitors (SSRIs), serotonin, SLP MIDD+ Virtual Conference, SLP2021MIDD
Division: Clinical Pharmacology and Pharmacometrics (CPP), PBPK

Introduction

  • In the CLARITY trial, a placebo-controlled, phase 2 trial of patients with major depressive disorder and inadequate response to selective serotonin reuptake inhibitors (SSRIs) or serotnin norepinephrine reuptake inhibitors (SNRIs), adjunctive pimavanserin was associated with statistically and clinically significant improvements on the 17=item Hamilton Depression Rating Scale (HAMD-17; primary endpoint measure), Clinical Global Impression-Improvement (CGI-I) scale, and Shehan Disability Scale (SDS)
  • Exposure-response (ER) models are progressively considered an integral part of clinical drug development and regulatory decision making.
  • ER models were developed based on data from the phase 2 CLARITY trial to assess the relationship between exposure and response (efficacy and safety).
  • Although pimavanserin is approved by the US Food and Drug Administration for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, the following information concerns an unapproved use of pimavanserin.

Presented at SLP MIDD+ Virtual Conference March 3-4, 2021