Objective: Evaluation of the efficacy and safety of a slow release low dose combination of pramipexole (PPX) and rasagiline (RAS) (P2B001) in a prospective double-blind placebo-controlled trial in early, untreated PD patients.

Background: Monoamine oxidase-B inhibitors or dopamine agonists are approved treatments for early PD patients but have potential efficacy or safety limitations. Pharma 2B’s product P2B001, contains low doses of PPX and RAS that have complementary mechanisms of action. We hypothesize that this combination will provide comparable efficacy but fewer adverse effects seen with higher doses of the individual components.  Preclinical studies in MPTP and 6-OHDA rodent models demonstrate that the combination provides synergistic effects, which are further enhanced if both agents are given as slow release.

Methods: Previously untreated subjects with early PD were equally randomized to treatment with P2B001 (0.3mg PPX/0.75mg RAS), P2B001 (0.6mg PPX/ 0.75mg RAS) or matching placebo in this 12-week trial. Study drug was taken once daily with no titration. The primary endpoint was the change from baseline to final visit in Total-UPDRS score I-III. Secondary measures included responder analyses of patients achieving ≥4 UPDRS point reduction, and changes in PDQ-39 and UPDRS activities of daily living and motor sub-scores.

Results: 149 subjects were randomized and 136 (91.3%) completed the study. The two P2B001 doses demonstrated robust statistically significant improvement in comparison to placebo for all primary and secondary endpoints. Adjusted mean change from baseline to final visit versus placebo in Total-UPDRS score was -4.67±1.28 points for the P2B001 0.6/0.75mg group (P=0.0004) and -3.84± 1.25 points for the 0.3/0.75mg group (P=0.0027). Significant benefits were also observed for both doses in all secondary outcomes including quality of life. Adverse events were generally comparable to placebo with the exception of nausea and somnolence, known adverse events of PPX that were generally transient and mild. No significant differences from placebo were found in Epworth Sleepiness Scale, reports of compulsive behavior or orthostatic hypotension. 

Conclusions: P2B001 provides significant clinical benefits with a good safety profile in early PD patients, suggesting a desirable initial treatment for early PD patients. 

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/slow-release-fixed-dose-combination-of-low-doses-pramipexole-and-rasagiline-p2b001-for-the-treatment-of-early-parkinsons-disease-pd/