A randomized trial of a low‐dose Rasagiline and Pramipexole combination (P2B001) in early Parkinson's disease

• Published in: Movement disorders Vol. 32; no. 5; pp. 783 - 789
• Main Authors: Olanow, C. Warren, Kieburtz, Karl, Leinonen, Mika, Elmer, Lawrence, Giladi, Nir, Hauser, Robert A., Klepiskaya, Olga S., Kreitzman, David L., Lew, Mark F., Russell, David S., Kadosh, Shaul, Litman, Pninit, Friedman, Hadas, Linvah, Nurit, the P2B Study Group, for
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2017
• Subjects: Activities of daily living; Aged; Antiparkinson Agents - therapeutic use; Benzothiazoles - therapeutic use; Clinical trials; Delayed-Action Preparations; Dopamine receptors; Double-Blind Method; Drug Combinations; Female; Humans; Indans - therapeutic use; Israel; Male; Middle Aged; Motor task performance; Movement disorders; Nausea; Neostriatum; Neurodegenerative diseases; Neuroprotective Agents - therapeutic use; P2B001; Parkinson Disease - drug therapy; Parkinson's disease; Pramipexole; Quality of life; Rasagiline; Severity of Illness Index; Triethylenemelamine; United States; P2B001; Parkinson's disease; Rasagiline; Pramipexole
• DOI: 10.1002/mds.26941
• ISSN: 0885-3185; 1531-8257

ABSTRACT Background Rasagiline and pramipexole act to improve striatal dopaminergic transmission in PD via distinct and potentially synergistic mechanisms. We performed a placebo‐controlled study to determine whether 2 doses of a novel slow‐release, low‐dose combination of rasagiline and pramipexole (P2B001) are effective and have a good safety profile in patients with early untreated PD. Methods Previously untreated patients with early PD were randomized (1:1:1) to once‐daily treatment with P2B001 (0.3 mg pramipexole/0.75 mg rasagiline), P2B001 (0.6 mg pramipexole/0.75 mg rasagiline) or placebo in a 12‐week multicenter double‐blind, placebo‐controlled trial. The primary endpoint was the change from baseline to final visit in Total‐UPDRS score versus placebo. Secondary measures included responder analyses of patients achieving ≥4 UPDRS point reduction, and changes in Parkinson Disease Quality of Life Scale–39 and UPDRS activities of daily living and motor scores. Results A total of 149 participants were randomized and 136 (91.3%) completed the study. Adjusted mean change from baseline to final visit versus placebo in Total‐UPDRS score was −4.67 ± 1.28 points for the P2B001 0.6/0.75 mg group (P = .0004) and −3.84 ± 1.25 points for the 0.3/0.75 mg group (P = .003). Significant benefits were also observed for both doses in the responder analysis (P = .0002 and P = .0001), Parkinson Disease Quality of Life Scale–39 scores (P = .05 and P = .01), and the UPDRS motor (P = .02 and P = .006) and activities of daily living (P = .005 and P = .0004) subscores. Adverse events of P2B001 were comparable to placebo apart from transient nausea and somnolence, which were more common with P2B001 treatment. Conclusions P2B001 offers a promising treatment option for patients with early PD with good clinical efficacy and a low risk of adverse events. © 2017 International Parkinson and Movement Disorder Society