Results from a phase 3 trial found that P2B001 was superior to its components in improving motor symptoms and daily function and was comparable with marketed doses of pramipexole.
P2B001 also produced less daytime sleepiness and fewer dopaminergic effects, said the investigators, who presented findings at the International Congress of Parkinson’s Disease and Movement Disorders.
Dr. Warren Olanow
The treatment studied, P2B001, is a proprietary, fixed-dose combination of extended-release (ER) formulations of pramipexole and rasagiline. Neither dose is currently available on the market.
Investigators wanted to test the hypothesis that two anti-Parkinsonian drugs that act through different mechanisms could work synergistically, providing benefits comparable with pramipexole but with fewer side effects, said lead study author Warren Olanow, MD, professor emeritus in the neurology and neuroscience departments at the Icahn School of Medicine at Mount Sinai, New York.
Pramipexole is problematic in that it causes dopaminergic and sleep-related side effects.
Laboratory studies have shown that low doses of pramipexole and rasagiline act synergistically, said Dr. Olanow. “A previous double-blind controlled study demonstrated that P2B001 was significantly superior to placebo with respect to efficacy (P < .001) and had a good safety and tolerability profile.”
P2B001 outperforms other formulations
The multicenter phase 3 study (NCT03329508) enrolled 544 patients aged 35-80 with early Parkinson’s disease to assess efficacy and safety of a daily dose of P2B001, compared with its components. Patients were randomized 2:2:2:1 to 12 weeks of treatment with P2B001; pramipexole ER 0.6 mg; rasagiline ER 0.75 mg, or to a calibration arm of marketed pramipexole-ER titrated to optimal dose (mean dose, 3.2 mg).
The primary endpoint compared baseline with week 12 changes in Unified Parkinson’s Disease Rating Scale total scores for P2B001 versus its individual components. The secondary endpoint compared baseline changes in Epworth Sleepiness Scale (ESS) for P2B001 versus pramipexole-ER.
P2B001 showed superior efficacy to each of its individual components and comparable efficacy with marketed doses of pramipexole-ER. It also yielded fewer adverse events related to dopaminergic side effects and less daytime sleepiness as measured by ESS. “Further, the drug is administered once a day and does not require titration,” said Dr. Olanow.
Levodopa-related benefits
Another advantage of starting early-stage patients on P2B001 is that it would give patients more time to be on an effective therapy with fewer side effects before going on levodopa, the current gold standard for Parkinson’s disease treatment.
Although the American Academy of Neurology recommends levodopa as initial therapy for Parkinson’s disease, the drug has been associated with a risk of developing motor complications.
“This opinion, however, was formulated prior to the availability of the results of the P2B001 study and should be reassessed in the light of the present study,” said Dr. Olanow. Longer-term studies should assess when and if patients will require levodopa therapy, as well as the long-term effects of P2B001 on the development of motor complications in patients with early Parkinson’s disease patients.
Investigators are preparing a regulatory market approval filing for P2B001 with the Food and Drug Administration.
Dr. Olanow is CEO of Clintrex Research Corporation, which has provided services to Pharma2B, sponsor of the phase 3 study. Pharma Two B is a private, late clinical-stage pharmaceutical company in Rehovot, Israel, that owns worldwide granted patents for P2B001 pharmaceutical composition and method of treatment.