2 results
122 Use of Pimavanserin in Patients With Parkinson’s Disease Psychosis: Subgroup Analysis of Efficacy and Safety in Patients With and Without Cognitive Impairment
- Daniel Weintraub, James Norton, Bruce Coate, Candace Andersson, Doral Fredericks, Clive Ballard
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- Journal:
- CNS Spectrums / Volume 23 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 15 June 2018, p. 77
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Objective
A planned subgroup analysis of a phase 3 study was performed to evaluate the efficacy and safety of pimavanserin (PIM) in Parkinson’s disease psychosis (PDP) patients withglobal cognitive impairment.
BackgroundPDP is frequent, distressing, a leading cause of institutionalization, complicates PD management and is linked to increased morbidity, incident dementia and mortality. PIM, a selective serotonin receptor (5-HT2A) inverse agonist/antagonist, is newly FDA-approved for the treatment of hallucinations and delusions associated with PDP.
MethodsIn Study 020, a 6-week FDA registration study, 199 patients with baseline Mini-Mental State Examination (MMSE) score ≥21, moderate-severe psychosis, and on stable PD meds, were randomized to PIM (34 mg/day) or placebo (PBO) for 6 weeks. This subgroup analysis evaluates efficacy and safety between two groups: those with MMSE total score ≥21 but <25 (cognitively impaired; equivalent to Montreal Cognitive Assessment [MoCA] score 15-19) and those with score ≥25 (cognitively normal; equivalent to MoCA score 20-30). Safety assessments were performed on the full safety dataset (i.e., three 6-week placebo-controlled studies) including 614 subjects (PIM=382, PBO=231).
ResultsOverall, patients in the PIM group experienced a statistically significant improvement in SAPS-PD scores from baseline to Day 43 compared with PBO (-5.79 vs. -2.73; p=0.001). In the subgroup analysis stratifying by baseline MMSE score, the change from baseline to Day 43 compared with PBO in the cognitively-impaired group (N=50) was numerically larger (-7.11 vs. -0.47; p=0.002). In the full safety dataset examining cognitively impaired patients, there were no between-group (PIM vs. PBO) differences in any treatment-emergent adverse event (TEAE) (57.6% vs. 56.1%) or serious TEAE (6.8% vs. 5.3%). The most common TEAEs occurring at ≥5% in either group were fall (7.4% vs.10.5%), confusional state (6.5% vs.1.8%), and orthostatic hypotension (0.0% vs. 8.8%).
ConclusionsIn this subgroup analysis of PDP patients, the treatment effect of PIM on SAPS-PD was larger in the cognitively-impaired group, with similar TEAE and serious TEAE rates. These results hold promise for cognitively-impaired patients that will be further elucidated in future studies.
Funding AcknowledgementsClinical study was funded by ACADIA Pharmaceuticals Inc.
135 Use of Pimavanserin in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs)
- James Norton, Doral Fredericks, Kathy Chi-Burris, Randy Owen
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- Journal:
- CNS Spectrums / Volume 23 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 15 June 2018, pp. 84-85
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- Article
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- You have access Access
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Study Objective
Psychosis is common in Parkinson’s disease (PD) and increases in both frequency and severity with disease duration. It is associated withincreased morbidity/mortality, complicates management of motor symptoms and often leads to long-term care placement. Pimavanserin is a selective 5-HT2A inverse agonist/antagonist approved in the U.S. for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Depression affects up to 60% ofPD patients and is frequently treated with SSRIs/SNRIs. Data suggest the potential for a synergistic effect between 5 HT2A receptor inverse agonist/antagonists and SSRIs insubjects with neuropsychiatric disease. This post-hoc analysis evaluated a subgroup of subjects from the pimavanserin clinical program to determine if there was any difference in antipsychotic response between the subjects receiving pimavanserin in combination with an SSRI versus those without.
MethodA pooled analysis of two 6-week randomized, double-blind, placebo-controlled Phase 3 studies was conducted to assess the overall treatment effect of pimavanserin34 mg. The outside-North America region in Study 012 was not included due to a difference in methodology in the assessment of the primary endpoint. Subjects in both the 020 and 012 studies received 42 days of treatment. The mITT population included 268 subjects; with 135 in the pimavanserin group. The full safety dataset included 433 subjects; with 202 in the pimavanserin group. Of the 268 subjects in the mITT population, a total of 77 received concomitant therapy with SSRIs. A subgroup analysis was conducted to determine if there was any difference in response among the subjects receiving concomitant SSRIs.
ResultsOverall, pimavanserin demonstrated a -6.21-point improvement in psychosis at Week 6 as measured by the PD-adapted Scale for Assessment of Positive Symptoms (primary change from baseline analysis [MMRM]). The treatment difference was 2.87 points over placebo (p<0.001) and was clinically meaningful. Both subgroups (pimavanserin +/- SSRI) demonstrated a statistically significant improvement over placebo. Among subjects taking concomitant SSRIs, the decrease in psychosis symptoms was more prominent for both pimavanserin and placebo-treated subjects (-8.33 points and -4.01 points, respectively) compared to the 189 subjects not taking SSRIs (-5.36 points and -3.01 points, respectively); the treatment difference was of greater magnitude in the concomitant SSRI treated group (-4.32 vs. -2.34). A total of 10% (4/40) and 7.4% (12/162) of pimavanserin treated subjects, with and without SSRIs, respectively, discontinued because of adverse reactions.
ConclusionsThe results of this analysis further support findings that the combination of selective 5-HT2A agonist/antagonists and SSRIs may have additive beneficial effects, suggesting a possible enhancement of antipsychotic effect in subjects treated with concomitant SSRIs.
Funding AcknowledgementsClinical study was funded by ACADIA Pharmaceuticals Inc.