- Clinical Trials
- Research News
- Industry Trends
- Agency Actions
- Drug Safety Issues
- Approvals, Launches, & New Indications
- Health Care Reform
Pimavanserin Meets Primary Endpoint in Phase III Parkinson’s Psychosis Trial
Antipsychotic efficacy significantly greater versus placebo (Nov. 27)
Pimavanserin (Acadia Pharmaceuticals) — a selective, non-dopaminergic serotonin 5-HT2A receptor blocker — has demonstrated antipsychotic efficacy (the primary endpoint) in a pivotal phase III study of patients with Parkinson’s disease psychosis (PDP). The drug also met the key secondary endpoint of motoric tolerability.
The multicenter, double-blind, placebo-controlled trial was designed to evaluate the efficacy, tolerability, and safety of pimavanserin as a treatment for patients with PDP. A total of 199 patients were randomly assigned to receive either 40 mg of pimavanserin or placebo once-daily for 6 weeks following a 2-week screening period, which included brief psycho-social therapy. Patients also received stable doses of their existing anti-Parkinson’s medications throughout the study.
The trial’s primary endpoint was antipsychotic efficacy, as measured using the Scale for Assessment of Positive Symptoms–Parkinson’s Disease (SAPS–PD), which consists of nine items from the hallucinations and delusions domains of the SAPS. These nine items have been shown to be relevant to the expression of psychotic symptoms in patients with Parkinson’s disease. Motoric tolerability, a key secondary endpoint in the study, was measured using parts II and III of the Unified Parkinson’s Disease Rating Scale (UPDRS).
Antipsychotic efficacy was determined by comparing the mean change from baseline to day 43 for pimavanserin versus placebo. The pimavanserin arm demonstrated a 5.79-point improvement in psychosis at day 43, compared with a 2.73-point improvement for placebo (P = 0.001).
The objective of the secondary endpoint (motoric tolerability) was to demonstrate that pimavanserin could achieve its antipsychotic effects without worsening motor function compared with placebo in patients with PDP. A prespecified non-inferiority analysis compared the mean change from baseline to day 43 for pimavanserin versus placebo. Motoric improvements were seen in both the pimavanserin and placebo arms. The confidence interval associated with the treatment difference did not exceed a pre-specified margin of 5 points for a clinically relevant change, confirming that pimavanserin met this key secondary endpoint and did not worsen motor function in PDP patients.
A secondary assessment of clinical global improvement showed a significant improvement (P = 0.001) with pimavanserin versus placebo.
In addition, other clinical benefits of pimavanserin were observed in exploratory efficacy measures of sleep and caregiver burden. Sleep was assessed using the Scale for Outcomes in Parkinson’s Disease (SCOPA)–Sleep scale, which was designed to enable investigators to evaluate nighttime sleep and daytime wakefulness in Parkinson’s patients. Pimavanserin demonstrated significant improvements in both nighttime sleep (P = 0.045) and daytime wakefulness (P = 0.012) on the SCOPA–Sleep scale compared with placebo.
Caregiver burden was assessed using the Caregiver Burden Scale (CBS). This scale was completed by caregivers to provide a quantitative assessment of burden associated with the patient’s functional/behavioral impairments, the circumstances of at-home care, and the caregiver’s health, social life, and interpersonal relations. Pimavanserin demonstrated a highly significant improvement versus placebo on the CBS (P = 0.002).
Consistent with previous studies, pimavanserin was safe and well tolerated in this study. Based on a preliminary analysis of the safety data, the most common adverse events were urinary tract infection (11.7% with placebo vs. 13.5% with pimavanserin) and falls (8.5% with placebo vs. 10.6% with pimavanserin). Adverse events were generally mild to moderate in severity.
Source: Acadia Pharmaceuticals; November 27, 2012.