Exposure-Response Modeling From the CLARITY Trial of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder

Conference: Psych Congress
Division: Cognigen


Pimavanserin displays selective inverse agonist and antagonist activity at 5-hydroxytryptamine-2A (5-HT2A) receptors with lesser activity at 5-HT2C receptors, and no appreciable activity at adrenergic, dopaminergic, histaminergic, or muscarinic receptors.

º Activity at these receptors has been implicated in a range of dose-limiting side effects associated with existing  antipsychotic drugs currently used as adjunctive treatment for depression.

º Due to its unique receptor binding profile, pimavanserin is under clinical investigation across multiple psychiatric indications.

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 serotonin 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 Sheehan 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,5 the following information concerns an unapproved use of pimavanserin.

Presented at the 33rd annual Psych Congress, September 10-13, 2020, Virtual.

By: Darwish M, Dirks B, Julie Pasarell, David Jaworowicz, Sebastien Bihorel, Howell B, Joel Owen, Stankovic S.