Evaluate the efficacy and safety of P2B001 compared with Extended-Release pramipexole (Prami-ER) in untreated Parkinson’s disease (PD).

P2B001 is an investigational, fixed low-dose, once-daily combination of ER formulations of pramipexole and rasagiline (0.6/0.75mg). We have previously reported that P2B001 provided significantly superior symptomatic efficacy compared to each of its components (primary efficacy endpoint). Here we report exploratory findings of P2B001 versus Prami-ER which was titrated for optimal efficacy and tolerability. 

This was an international, multicenter, randomized, double-blind, parallel-group study in patients with early untreated PD comparing once-daily P2B001 to its individual components and to optimally titrated Prami-ER (mean dose of 3.2mg). Eligible patients were aged 35–80y, <3 years from PD diagnosis, and not receiving anti-parkinsonian therapy.  Exploratory endpoints are presented along with nominal p-values.

Changes from baseline to week 12 in total UPDRS (Part II+III) scores between P2B001 and Prami-ER were not significantly different (-8.35 ±0.86 vs 7.98 ±0.6); post-hoc analysis confirmed non-inferiority of P2B001 to Prami-ER (margin of 3 points, p=0.0052). Likewise, there were no significant differences between P2B001 and Prami-ER on UPDRS Part II (activities of daily living) or Part III (motor) scores. Overall, 74.1% of patients receiving P2B001 and 76.6% of patients receiving Prami-ER showed ≥4-point improvement in UPDRS Total scores (Odds ratio 0.87 [0.44, 1.75]; p=0.70). Overall, 74.7% of patients experienced ≥1 TEAE with P2B001 versus 86.5% with titrated Prami-ER and there was a lower frequency of dopaminergic-related TEAEs (44.7% versus 66.2%, respectively). Rates of somnolence (14.7% versus 31.1%) and orthostatic hypotension (2.7% versus 12.2%) were also lower with P2B001 compared with Prami-ER. 

These data indicate that P2B001 offers a once daily treatment option (without the need for titration) for patients with early PD with comparable efficacy to marketed Prami-ER but with reduced sleep-related and dopaminergic side effects.