Parkinson's Disease and P2B001 Study

Parkinson's disease (PD) is a brain disorder that leads to shaking, stiffness, and difficulty with walking, balance, and coordination. Parkinson's symptoms usually begin gradually and get worse over time.

Levodopa is considered to be the most effective treatment for PD, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders.

An experimental drug that combines fixed doses of extended-release (ER) formulations of existing medications can significantly reduce symptoms in patients with untreated early-stage PD, new research suggests. The findings were presented at the American Academy of Neurology (AAN) 2022 Annual Meeting.

Researchers used P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected to have synergistic effects. Tracing the results from an earlier trial, researchers launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001 compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early PD. Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5 to 4.5 mg).

Results

• Adjusted mean change from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 vs pramipexole (P = .0018) and -3.30 points for P2B001 vs rasagiline (P = .0001).
• There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
• The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 vs pramipexole ER was -2.66 points (P < .0001).
• In addition, fewer dopaminergic adverse events were reported with the combination drug vs pramipexole ER (44.7% vs 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs 12.2%).

Researchers concluded that "As a first-line treatment, P2B001 could offer an effective option instead of levodopa. It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications."

Reference: https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.26941