The following is a summary of “A Randomized Phase 3 Study Comparing P2B001 to its Components (Low-Dose Extended-Release Rasagiline and Pramipexole) and to Optimized Doses of Marketed Extended-Release Pramipexole in Early Parkinson’s Disease,” published in the October 2023 issue of Neurology by Olanow et al.
The best way to start treatment for Parkinson’s disease (PD) to get the most benefits and the fewest side effects is still unknown. Researchers performed a retrospective study to assess the superiority of P2B001 over its components and compare its safety and efficacy to optimized pramipexole-ER in early PD.
About 544 untreated PD patients were randomly assigned in a 2:2:2:1 ratio to one of four treatment groups, namely P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or a commercially available titrated dose of pramipexole-ER (ranging from 1.5 mg to 4.5 mg). The primary endpoint was to assess changes from baseline to week 12 in the Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was to measure the Epworth Sleepiness Scale (ESS) change for P2B001 compared to the titrated dose of pramipexole-ER.
The result demonstrated P2B001 showed better effectiveness compared to its individual components, with UPDRS II+III score differences of -2.66 (95% CI, -4.33 to -1.00) vs. pramipexole-ER 0.6 mg (P = 0.0018) and -3.30 (95% CI, -4.96 to -1.63) vs. rasagiline-ER 0.75 mg (P < 0.0001). P2B001 showed similar efficacy to titrated pramipexole-ER (mean, 3.2 mg) but resulted in significantly less daytime sleepiness (ESS treatment difference: -2.66 [95% CI, -3.50 to -1.81]; P < 0.0001). P2B001 was well-tolerated with fewer sleep-related and dopaminergic side effects than titrated pramipexole-ER, including somnolence, orthostatic hypotension, and neuropsychiatric effects.
The study found that once-daily P2B001 has superior efficacy and better tolerability than its components and commercially used doses of pramipexole-ER as initial therapy for early PD.