ENHANCE: Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin for Schizophrenia in Patients With an Inadequate Response to Antipsychotic Treatment

Abstract Inadequate response to antipsychotic treatment is common in patients with schizophrenia. This study evaluated pimavanserin, a 5-HT2A receptor inverse agonist/antagonist, as adjunctive inadequate response. was 6-week, randomized, double-blind, placebo-controlled, conducted North America and Europe. Adult outpatients schizophrenia current were enrolled. Inclusion criteria included Positive Negative Syndrome Scale (PANSS) total score ≥65 ≤110 retrospective stability of 8 weeks. Pimavanserin 20 mg/day or placebo added ongoing tested flexible-dose paradigm dose adjustments allowed during the first 3 The primary efficacy endpoint, PANSS change from baseline week 6, not met, although improvement greater pimavanserin than (LS mean difference: –2.1, [95% CI: –4.5, 0.4]; P = .094). As hierarchical testing procedure used, additional analyses exploratory. Clear separation observed at 6 for Symptoms subscale –0.7, –1.5, 0.0]) Marder Symptom Factor (–0.9, [–1.7, –0.1]). Analysis European sites (81.5% patients) revealed difference versus on –3.1, –5.8, –0.4]) Clinical Global Impressions–Severity (–0.2, [–0.4, –0.0]). Treatment-emergent adverse events occurred 39.9% 36.4% placebo. Although statistical significance endpoint trend toward negative symptoms warranting further study.