Clinical Trials

Date: 2015-08-06

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in The Journal of the American Medical Directors Association

Company: Acadia Pharmaceuticals (USA - CA)

Product: Nuplazid™ (pimavanserin)

Action mechanism:

• selective serotonin inverse agonist. Nuplazid™ is an selective serotonin inverse agonis(SSIA) preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in Parkinson’s disease psychosis. The unique pharmacology of Nuplazid™  establishes a new class of drug - selective serotonin inverse agonists (SSIA) - by not only preferentially targeting 5-HT2A receptors but also avoiding activity at dopamine and other receptors commonly targeted by antipsychotics.Nuplazid™ was granted Breakthrough Therapy designation from the FDA in 2014.

Disease: psychosis associated with Parkinson’s disease

Therapeutic area: Neurodegenerative diseases - Psychiatric diseases - Mental diseases

Country:

Trial details:

Latest news:

• • On August 6, 2015, Acadia Pharmaceuticals announced the publication of new data from its ongoing open-label safety extension study, the -015 Study, with Nuplazid™ (pimavanserin) in patients with Parkinson’s disease psychosis (PDP) in the July 31 online issue of the Journal of the American Medical Directors Association. This is the first published report evaluating the long-term impact of antipsychotics on mortality and serious adverse events in patients with PDP. In the -015 study, all patients received Nuplazid™ (40 mg). Of 423 patients assessed, 357 received Nuplazid™ only, while 66 patients received a currently marketed antipsychotic prescribed by their physician at some point during the study in addition to Nuplazid™. The two groups were well matched at baseline with regard to age (mean of 71-72 years) and other demographic and baseline variables. In a post-hoc analysis, there was a significant increase in the mortality rate of patients who received concurrent treatment with a currently marketed antipsychotic (18.8 deaths per 100 person-years since the first concurrent antipsychotic dose) compared to those who received Nuplazid™ only (4.5 deaths per 100 person-years). There also was a significant increase in treatment emergent serious adverse events in patients who received concurrent treatment with a currently marketed antipsychotic (52.5 first-occurrence events per 100 person-years since the first concurrent antipsychotic dose) compared to those who received Nuplazid™ only (17.8 first-occurrence events per 100 person-years).
• • On June 16, 2015, Acadia Pharmaceuticals announced the presentation of integrated efficacy and tolerability data from its Phase III program with Nuplazid™ at the 19th International Congress of Parkinson’s Disease and Movement Disorders held in San Diego. Poster Presentations are:
• Efficacy and Tolerability of Nuplazid™ (pimavanserin) in PD Psychosis: Analysis of an Integrated Phase 3 Placebo-Controlled Dataset (Abstract #156) - An integrated analysis was performed on efficacy and tolerability data from two six-week Phase III placebo-controlled clinical trials with Nuplazid™ (40 mg) in Parkinson’s disease psychosis (PDP). In this large pooled sample of 268 patients from North America, Nuplazid™ showed highly significant improvement in psychosis compared to placebo on the 9-item SAPS-PD scale (p<0.001). Nuplazid™ demonstrated significant improvement on each of the separate hallucinations and delusions domains and also on secondary psychoses measures, including the Clinical Global Impression-Improvement (CGI-I) and the Clinical Global Impression-Severity (CGI-S) scales. In addition, Nuplazid™ demonstrated significant improvement on nighttime sleep, daytime wakefulness and caregiver burden, representing additional potential clinically impactful benefits. Results were consistent across all subgroups of interest, showing greater improvement with Nuplazid™ over placebo regardless of age, sex, race group or MMSE screening score. Pooled analysis of data from all Phase III placebo-controlled clinical trials with Nuplazid™ showed that Nuplazid™ was well tolerated and had no impairment on motor function. The adverse event profile of Nuplazid™ was similar to placebo.
• Long-Term Effectiveness of Nuplazid™ (pimavanserin) in PD Psychosis: Data from 2 Open-Label Studies (Abstract #149) -  Data from two open-label safety extension studies were presented, including final data from a completed Phase II open-label study (-010 Study) of 39 PDP patients and interim data from an ongoing Phase III open-label study (-015 Study) of 459 PDP patients. The interim analysis of the ongoing -015 Study reflects data entered into the database as of December 13, 2013. PDP patients in the -015 Study rolled in after completing 6 weeks of blinded treatment in a Phase III placebo-controlled efficacy, tolerability and safety trial. PDP patients in the -010 Study rolled in following completion of the 4-week treatment period in a Phase II placebo-controlled efficacy, tolerability and safety trial. In both open-label studies, patients remained on treatment for a median duration of over 15 months.
• Data from the two open-label studies suggest that long-term administration of Nuplazid™ is generally safe and well tolerated in patients with PDP. Although there are no formal efficacy endpoints in the open-label studies, persistent antipsychotic benefit has been observed in one or both studies across measures including SAPS-PD, other SAPS-based outcomes, CGI-I and CGI-S. In the -015 Study, patients who rolled in from a placebo arm showed a highly significant improvement in SAPS-PD and CGI-S scores at Week 4 compared to their score at the end of the 6-week randomized study. This improvement was observed for the combined U.S. and rest-of-world patients. Persistent benefit on caregiver burden with Nuplazid™ has also been observed.

Is general: Yes