Abstract Details

Title Safety and Tolerability of P2B001 in Patients with Early Parkinson’s Disease: Analysis of an Integrated Phase 2 and 3 Safety Database

Topic Movement Disorders

Presentation(s) S30 - Movement Disorders: Clinical Trials in Movement Disorders (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Background

P2B001 is a once-daily, no titration, combination of low-dose, extended-release (ER) formulations of pramipexole and rasagiline (0.6/0.75mg), under investigation for patients with early Parkinson’s disease (PD). We have previously reported that P2B001 provides superior symptomatic efficacy to placebo and its components, and comparable efficacy with commercially available ER-Pramipexole (PramiER) titrated to optimal dose (mean 3.2mg).

Objective

Evaluate and characterize the safety and tolerability profile of P2B001.

Design/Methods

Integrated safety analysis of phase 2 (NCT01968460) and phase 3 (NCT03329508) randomized, controlled, 12-week studies.

Results

The integrated analysis included 199 patients with early PD (69% male; mean±SD age 63.8±9.2 years; time from diagnosis 5.9±7.9 months) who received P2B001. Overall, 118 (59%) patients reported ≥1 treatment-related AE (vs. 36% with placebo [n=50] and 70% with PramiER [n=74]); no serious-related AEs were reported with P2B001. Most (142/149, 95%) events reported with P2B001 were of mild-moderate intensity. Common AEs were nausea (19% vs. 2% with placebo and 23% withPramiER), somnolence (16% vs. 0 with placebo and 31% with PramiER), fatigue (14% vs. 2% with placebo and 18% with PramiER), dizziness (11% vs 8% with placebo and 10% with PramiER), and insomnia (8% vs. 4% with placebo and 10% with PramiER); other AEs were reported in ≤5% of patients. There was a lower frequency of dopaminergic TEAEs with P2B001 compared with PramiER (45.7% vs 66.2%, respectively); whereas these mostly emerged in the first 4 weeks of P2B001 treatment, the increased frequency persisted with PramiER. In the phase 3 study, there was no worsening from baseline in QUIP-RS-Total-Score in either the P2B001 or PramiER groups (change of -1.49 and -0.66, respectively).

Conclusions

P2B001 may offer patients with early PD a convenient, first-line, once-daily treatment with a favorable safety and tolerability profile compared to commercially available PramiER. P2B001-related AEs were mainly mild-moderate; no ICD-related concerns were observed.

Authors/Disclosures
Joy A. DeMarcaida, MD (Hartford Healthcare Movement Disorders Center) PRESENTER	The institution of Dr. DeMarcaida has received research support from Pharma2B. The institution of Dr. DeMarcaida has received research support from Neuroderm. The institution of Dr. DeMarcaida has received research support from Sage Therapeutics.
Pninit Litman, PhD (Pharma2b LTD)	Dr. Litman has received personal compensation for serving as an employee of PHARMA 2B.
Hadas Friedman, Other (Pharma Two B)	Mrs. Friedman has received personal compensation for serving as an employee of Pharma Two B.
Cheryl Fitzer-Attas, PhD (ClinMed LLC)	Dr. Fitzer-Attas has received personal compensation for serving as an employee of Mitsubishi Tanabe Pharma America. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Cyclerion. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Pharma Two B. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Golden Heart Flower. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for B-Portal Biologics. Dr. Fitzer-Attas has stock in Golden Heart Flower.