Abstract Details

P2B001 is novel, fixed-dose, once-daily combination of ER formulations of pramipexole and rasagiline (0.6/0.75mg), both components at low doses that are not individually available on the market.

Evaluate the efficacy and safety of P2B001 compared with its components and with generic Extended-Release pramipexole (ER-PPX, calibration arm) in early Parkinson’s disease (PD).

Untreated patients (35-80 years, disease duration <3 years) were randomized double-blind (2:2:2:1) to 12-weeks treatment with P2B001, pramipexole-ER (PPX) 0.6mg, rasagiline-ER (RAS) 0.75mg, or marketed ER-PPX (titrated). The primary efficacy endpoint compared the change from baseline to Week 12 in UPDRS-Total score (Parts II+III) for P2B001 with its individual components. The first secondary endpoint compared the change from baseline in Epworth Sleepiness Scale (ESS) for P2B001 versus ER-PPX.

519 patients were randomized and treated (P2B001 =150, PPX 0.6mg =148, RAS 0.75mg =147, ER-PPX =74) and 90-93% per group completed 12-weeks treatment. P2B001 provided significantly superior symptomatic efficacy to its components; mean ±SE change in UPDRS-Total scores were -7.98 ±0.60 for P2B001 compared to -5.32 ±0.61 for PPX 0.6mg (treatment difference [TD]: -2.66 [-4.33, -1.00]; p=0.0018) and 4.69 ±0.61 for RAS 0.75mg (TD: -3.30 [-4.96, -1.63]; p=0.0001). P2B001 showed comparable efficacy to ER-PPX (TD: 0.37 [-1.67, 2.42]; p=0.71) with significantly less daytime sleepiness (mean ±SE changes from baseline in ESS-Total scores were -0.33 ±0.25 for P2B001 vs. 2.33 ±0.36 for ER-PPX (TD: -2.66 [-3.50, -1.81]; p<0.0001)). Fewer dopaminergic adverse events were reported with P2B001 vs ER-PPX (44.7% vs 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).

The study met its primary and secondary endpoint and treatment was well-tolerated with fewer dopaminergic AEs than ER-PPX. These findings support the potential of P2B001 as a first-line, once-daily treatment for people with early PD that offers effective symptomatic control with a favorable safety profile and no need for titration.