An Open-Label, 8-Week Study of Safety and Efficacy of Pimavanserin Treatment in Adults with Parkinson's Disease and Depression

Abstract

Background: Many patients with Parkinson's disease (PD) experience depression.

Objective: Evaluate pimavanserin treatment for depression in patients with PD.

Methods: Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale-17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in patients who received ≥1 pimavanserin dose.

Results: Efficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was -10.8 (0.63) (95% CI, -12.0 to -9.5; p < 0.0001) with significant improvement seen at week 2 (p < 0.0001) and for both monotherapy (week 8, -11.2 [0.99]) and adjunctive therapy (week 8,-10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n = 7; 14.9%) and psychiatric (n = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III.

Conclusion: In this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD.

Keywords: Parkinson’s disease; adjunctive therapy; dementia; depression; monotherapy; pimavanserin.

Conflict of interest statement

DD, BC, LJ, RN, VA: are employees of and hold stock and/or stock options in ACADIA Pharmaceuticals Inc.

JCN: was an employee of ACADIA Pharmaceuticals Inc. at the time of this study.

GA: has received research support from Accera, Allergan, Axovant, Eisai, Genentech, Intra- Cellular, Janssen, Lundbeck, Neurim, Neurotrope, Novartis, Otsuka, Roche, Suven, and TransTech and has served on the speakers bureau or as a consultant for ACADIA, Alkermes, Allergan, Avanir, Janssen, Lundbeck, Merck, Nestlé, Otsuka, Sunovion, Takeda, and Vanda.

JLA: has received research support from Abbott, AbbVie, ACADIA, Biogen, Boston Scientific, Denali, Impax, NeuroDerm, Sunovion, and Theravance and has received honoraria from Abbott, AbbVie, Acorda, Adamas, Allergan, Boston Scientific, Medtronic, Teva, and US WorldMeds.

MC is a consultant to ACADIA, Kyowa Kirin, Sunovion, and Reviva.

Figures

Fig. 1

Study design. PD, Parkinson’s disease; SNRI, serotonin/norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

Fig. 2

Change from baseline in HAMD-17 (A) total score over 8 weeks and (B) individual item scores at week 8 in all patients included in efficacy analyses. BL, baseline; HAMD-17, Hamilton Depression Scale–17-item version; LS, least squares; SE, standard error.

Fig. 3

Change in HAMD-17 from baseline by treatment with pimavanserin as (A) monotherapy and (B) adjunctive therapy. BL, baseline; HAMD-17, Hamilton Depression Scale–17-item version; LS, least squares; SE, standard error.

Fig. 4

Impact on (A) CGI-S and (B) CGI-I scores over 8 weeks in all patients included in efficacy analyses. BL, baseline; CGI-I, Clinical Global Impression–Improvement; CGI-S, Clinical Global Impression–Severity; LS, least squares; SE, standard error.

Fig. 5

Change from baseline to week 8 in (A) SCOPA-GS, (B) SCOPA-NS, and (C) SCOPA-DS in all patients included in efficacy analyses. BL, baseline; LS, least squares; SCOPA-DS, Scale for Outcomes in Parkinson’s Disease–daytime sleepiness; SCOPA-GS, Scale for Outcomes in Parkinson’s Disease–global sleep; SCOPA-NS, Scale for Outcomes in Parkinson’s Disease–nighttime sleep; SE, standard error.

Fig. 6

Change from baseline to week 8 in EQ-5D-5L-VAS in all patients included in efficacy analyses. BL, baseline; EQ-5D-5L-VAS, EuroQol-5 Dimensions-5 Levels version 1 visual analog scale; LS, least squares; SE, standard error.

Fig. 7

Change from baseline to week 8 in MDS-UPDRS Part III in all patients included in safety analysis. BL, baseline; LS, least squares; MDS-UPDRS Part III, Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III; SE, standard error.