Objective: Evaluate the efficacy and safety of P2B001 compared with its components and with Extended-Release pramipexole (ER-PPX, calibration arm) in untreated PD.

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

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

Results: 544 patients were enrolled (67.8% male; mean age: 64.6y; time since diagnosis: 5.2 months; UPDRS-Total score: 30.8) and 519 were randomized and treated (P2B001 =150, PPX 0.6mg =148, RAS 0.75mg =147, ER-PPX =74); 90-93% per group completed 12-weeks of treatment. P2B001 provided significantly superior symptomatic efficacy compared to each of its components; LSM ±SE change in UPDRS-Total scores were -7.98 ±0.60 for P2B001 vs -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 provided comparable efficacy to ER-PPX (TD: 0.37 [-1.67, 2.42]; p=0.71) with significantly less daytime sleepiness based on ESS (LSM ±SE change from baseline was -0.33 ±0.25 for P2B001 vs 2.33 ±0.36 for ER-PPX (TD: -2.66 [-3.50, -1.81]; p<0.0001)). Responder rates (≥4 point improvement in UPDRS-Total scores) were 74.3% with P2B001, 59.8% with PPX 0.6mg, 55.7% with RAS 0.75mg and 75.8% with ER-PPX. 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%).

Conclusion: The study met its primary and secondary efficacy 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 may offer effective symptomatic control with a favorable safety profile and no need for titration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/p2b001-in-the-management-of-untreated-pd-results-from-a-randomized-double-blind-double-dummy-controlled-trial/