Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study)
LeWitt PA et al. – The evidence of efficacy in the US subgroup suggested that fipamezole at 90 mg TID may be useful to treat levodopa–induced dyskinesias (LID) in Parkinson disease (PD) without exacerbating parkinsonism.Methods
- This was a double-blind, randomized, placebo-controlled, dose-escalating 28-day study in levodopa-treated patients with PD experiencing LID, conducted at 25 centers in the United States (115 subjects) and 7 centers in India (64 subjects).
- Dyskinesias were evaluated 3 times after subjects became “on” from levodopa.
- Outcome assessment was performed with analysis of variance, which evaluated fipamezole dose-effects in a hierarchical stepwise manner and the Jonckheere test for dose responsiveness.
- The total study population showed no statistically significant primary endpoint difference.
- However, because of inhomogeneity recognized between US and Indian study populations, a prespecified subgroup analysis of US subjects was conducted, showing fipamezole at 90 mg reduced LID (mean, 95% CI, LID rating improvement vs placebo -1.9 [0.0 to -3.8; p=0.047]).
- Dose responsiveness was demonstrated (p=0.014 for placebo, 30, 60, and 90 mg fipamezole).
- Fipamezole induced mild, transient blood pressure elevation and was associated with an acceptable profile of adverse effects.