Objective: To investigate the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the dopamine transporter antagonist brasofensine (BMS-204756) in patients with Parkinson's disease receiving levodopa/carbidopa treatment.

Methods: A 4-period crossover study was performed in 8 men (mean age 66 y) with moderate Parkinson's disease (Hoehn-Yahr stage II-IV). A dose escalation study was used in which each patient was given a single oral dose of brasofensine 0.5, 1, 2, or 4 mg, which was coadministered with the patient's usual dose of levodopa/carbidopa.

Results: The maximum concentration (Cmax) values of brasofensine observed in plasma after oral administration were 0.35, 0.82, 2.14, and 3.27 ng/mL for the 0.5-, 1-, 2-, and 4-mg doses, respectively; these concentrations occurred 4 hours (time to Cmax) after administration in all cases. Exposure to brasofensine (based on AUC0-infinity) increased at a rate greater than proportional to dose. Based on the motor performance subscale of the Unified Parkinson's Disease Rating Scale, no change in patient disability was observed at any dose level.

Conclusions: Brasofensine was safe and well tolerated in the patient cohort studied at daily doses of up to 4 mg. Adverse events were generally mild in intensity, and included headache, insomnia, phlebitis, dizziness, ecchymosis, and vomiting.