PMID- 22744665
OWN - NLM
STAT- MEDLINE
DCOM- 20121004
LR  - 20140731
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 79
IP  - 2
DP  - 2012 Jul 10
TI  - Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease 
      (FJORD study).
PG  - 163-9
LID - 10.1212/WNL.0b013e31825f0451 [doi]
AB  - OBJECTIVE: Fipamezole, a selective alpha2-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 U.S. 
      and Indian study populations, a prespecified subgroup analysis of U.S. 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.
FAU - Lewitt, Peter A
AU  - Lewitt PA
AD  - Departments of Neurology, Henry Ford Hospital, Detroit, MI, USA. 
      plewitt1@hfhs.org
FAU - Hauser, Robert A
AU  - Hauser RA
FAU - Lu, Mei
AU  - Lu M
FAU - Nicholas, Anthony P
AU  - Nicholas AP
FAU - Weiner, William
AU  - Weiner W
FAU - Coppard, Nicholas
AU  - Coppard N
FAU - Leinonen, Mika
AU  - Leinonen M
FAU - Savola, Juha-Matti
AU  - Savola JM
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20120627
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Imidazoles)
RN  - 0 (Indans)
RN  - 0 (Placebos)
RN  - 46627O600J (Levodopa)
RN  - T5RCK09KHV (fipamezole)
SB  - IM
MH  - Aged
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Dyskinesia, Drug-Induced/*drug therapy/etiology
MH  - Female
MH  - Humans
MH  - Imidazoles/*administration & dosage
MH  - Indans/*administration & dosage
MH  - Levodopa/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Parkinson Disease/complications/*drug therapy
MH  - Placebos
MH  - Severity of Illness Index
MH  - Treatment Outcome
EDAT- 2012/06/30 06:00
MHDA- 2012/10/05 06:00
CRDT- 2012/06/30 06:00
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2012/10/05 06:00 [medline]
AID - WNL.0b013e31825f0451 [pii]
AID - 10.1212/WNL.0b013e31825f0451 [doi]
PST - ppublish
SO  - Neurology. 2012 Jul 10;79(2):163-9. doi: 10.1212/WNL.0b013e31825f0451. Epub 2012 
      Jun 27.