CLARITY: A Phase 2 Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder

This study examined pimavanserin (PIM), a 5-HT2A receptor inverse agonist/antagonist, as a potential adjunct to SSRIs or SNRIs for major depressive disorder (MDD). Adult female and male patients with MDD, inadequate response to ongoing SSRI/SNRI therapy, and a MADRS total score >20 were randomized to PIM 34 mg/day or placebo (PBO) added to their SSRI/SNRI treatment. A sequential parallel comparison design was used, consisting of two 5-week stages. PBO non-responders in Stage-1 were re-randomized to PIM or PBO for the second period (Stage-2). Of 207 patients enrolled, 52 received PIM and 155 received PBO in Stage 1. PIM met the primary endpoint, reducing the weighted Stage-1/Stage-2 HAMD-17 total score significantly more than PBO (P=0.04). Stage-1 PIM patients demonstrated highly significant 5-week improvement on the HAMD-17 (P < 0.001; effect size, Cohen’s d: 0.626). Stage-2 results showed non-significant separation among Stage-1 placebo non-responders (P=0.69), partly due to fewer subjects being randomized (n=58) than planned. Nevertheless, greater improvement was seen with PIM on the Sheehan Disability Scale (P=0.004), and on 7 of the 11 other secondary endpoints, including responder rate (≥50% reduction in HAMD-17 total; P=0.007), Massachusetts General Hospital Sexual Functioning Index (P < 0.001), and Karolinska Sleepiness Scale for daytime sleepiness (P=0.02). PIM treatment was well tolerated, and safety results were consistent with previous findings. Study data provide evidence of the efficacy, safety, and tolerability of adjunctive pimavanserin in treating MDD inadequately responsive to SSRI or SNRI therapy. However, efforts to confirm these results are ongoing in a Phase-3 program.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.