Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study)
| Autor: | Juha Savola, Peter A LeWitt, Nicholas Coppard, William J. Weiner, Mika Leinonen, Robert A. Hauser, Mei Lu, Anthony P. Nicholas |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Dyskinesia Drug-Induced medicine.medical_specialty Levodopa Subgroup analysis Placebo Severity of Illness Index Gastroenterology Drug Administration Schedule law.invention Placebos Double-Blind Method Randomized controlled trial law Internal medicine Severity of illness medicine Clinical endpoint Humans Aged business.industry Parkinsonism Imidazoles Parkinson Disease Middle Aged medicine.disease Surgery Treatment Outcome Dyskinesia Indans Female Neurology (clinical) medicine.symptom business medicine.drug |
| Zdroj: | Neurology. 79:163-169 |
| ISSN: | 1526-632X 0028-3878 |
| Popis: | Objective: Fipamezole, a selective α 2 -adrenergic receptor antagonist, reduced levodopa-induced dyskinesias (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. In 10 dyskinetic subjects with Parkinson disease (PD), a proof-of-concept study showed beneficial effects at single doses of 60 and 90 mg. The primary study objective was to assess suppression of LID by fipamezole at day 28, as measured by the Levodopa-Induced Dyskinesia Scale (LIDS), a modification of the Abnormal Involuntary Movement Scale. 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. Results: 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. Conclusions: The evidence of efficacy in the US subgroup suggested that fipamezole at 90 mg TID may be useful to treat LID in PD without exacerbating parkinsonism. Classification of evidence: This study provides Class III evidence that fipamezole is well-tolerated and, in the US subpopulation, lessens LID at 90 mg TID. |
| Databáze: | OpenAIRE |
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