SEATTLE — Parkinson’s disease patients did better taking two drugs than one in a pivotal trial, a researcher said here.
Scores on standard tests improved more among patients taking a fixed-dose combination of 0.6 mg of immediate-release pramipexole and 0.75 mg of rasagiline — dubbed P2B001 — than with either agent alone, said C. Warren Olanow, MD, of the Icahn School of Medicine at Mount Sinai in New York City.
P2B001 also outperformed an extended-release version of pramipexole (Mirapex ER) titrated to doses of 1.5-4.5 mg, he told attendees at a late-breaker session during the American Academy of Neurology’s annual meeting. The efficacy was similar, but patients receiving the combination had less daytime sleepiness and other dopaminergic side effects typical of higher-dose pramipexole.
The two-drug polypill is also attractive because its one-size-fits-all dosing, supported in multiple studies, means patients and clinicians can skip the dose titration recommended for current therapies. Moreover, said Olanow, it could be suitable as first-line therapy.
If approved, P2B001 would be a “new option for initiating treatment” in Parkinson’s disease, he said.
Pramipexole, of course, is a dopamine agonist, while rasagiline is a monoamine oxidase inhibitor. Current treatment guidelines put these drug classes as second- and third-line therapy, respectively, after levodopa, because their better efficacy comes with more side effects. In addition to somnolence, these include gastrointestinal problems, orthostatic hypotension, and psychobehavioral symptoms such as hallucinations and diminished impulse control.
For the phase III study, Olanow and colleagues enrolled 544 previously untreated patients with early Parkinson’s disease (<3 years since diagnosis) at 70 centers in multiple countries. Patients were randomized at 2:2:2:1 to receive capsules combining low-dose pramipexole with rasagiline, to each of these alone, and to extended-release pramipexole for 12 weeks.
The primary outcome measure was the total Unified Parkinson’s Disease Rating Scale (UPDRS) score (i.e., parts II and III). Patients receiving the combination showed an improvement of about 8 points relative to baseline, versus approximately 5.5 points for both of the components individually.
With respect to pramipexole ER, changes in UPDRS score were virtually identical. But Epworth Sleepiness Score ratings jumped almost immediately in patients receiving pramipexole ER and stayed elevated through the 12-week study. There was no change from baseline in the P2B001 group.
Rates of other adverse effects also favored the combination. For example, orthostatic hypotension was identified in 13% of the pramipexole ER group versus 3% of those on P2B001. Nausea, constipation, and peripheral edema were also more common with pramipexole ER. Overall, the safety profile for P2B001 was as expected given its components (e.g., somnolence was still present at rates similar to those seen with low-dose pramipexole alone).
The study was funded by Pharma Two B, developer of P2B001. Several co-authors were company employees. Olanow reported a financial relationship with Pharma Two B.