Safety and Efficacy Study of Fipamezole in Treatment of Motor Dysfunctions in Parkinson's Disease (Fjord)

The purpose of this study is to determine whether Fipamezole is effective in the treatment of levodopa-induced dyskinesia in advanced Parkinson's disease.

This study is a multi-center, double-blind, placebo-controlled, multiple dose escalating, safety, tolerance, pharmacokinetics, and efficacy study of fipamezole administered in Parkinson's disease patients who are concomitantly being treated with a combination product of levodopa with a dopamine decarboxylase inhibitor (DDI) and possible other antiparkinson medication. Approximately 30 sites in the US and India will participate in this study. The patients will be randomized into one of four treatment arms to receive either fixed or ascending doses of Fipamezole (from 30 to 90 mg tid) or placebo. For efficacy assessments, levodopa-induced dyskinesia is assessed using a standardised rating scale. Time spent in 'Off' state or in 'On' state without dyskinesia, 'On' with non-troublesome dyskinesia or 'On' with troublesome dyskinesia, is assessed using patient diaries. Impact of dyskinesia on daily activities is quantified using a PDYS-26 questionnaire. To explore potential positive or negative impact of Fipamezole on cognitive functions, the study includes two cognitive tests. Finally, the study includes investigator assessments of CGI-I scales for dyskinesia, Parkinson's disease, and clinical condition in general.

• Placebo Comparator: 1
  One placebo tablet administered tid from Day 1 to 28
  Intervention: Drug: fipamezole
• Active Comparator: 2
  One 30-mg tablet of Fipamezole tid from Day 1 to 28
  Intervention: Drug: fipamezole
• Active Comparator: 3
  One 30-mg tablet of Fipamezole tid from Day 1 to 7; and one 60-mg tablet of Fipamezole tid from Day 8 to 28
  Intervention: Drug: fipamezole
• Active Comparator: 4
  One 30-mg tablet of Fipamezole tid from Day 1 to 7; one 60-mg tablet of Fipamezole tid from Day 8 to 14; and one 90-mg tablet of Fipamezole tid from Day 15 to 28
  Intervention: Drug: fipamezole

Main Inclusion Criteria:

• Idiopathic Parkinson's disease.
• Levodopa/DDI associated peak-dose dyskinesia which is at least moderately disabling and present for ≥25% of the waking day (UPDRS part IV, items 32 and 33, each ≥ 2).
• Stable Parkinson's medication for at least 1 month prior to randomization.
• Hoehn and Yahr Stages 1 to 4 during 'Off' period.
• Demonstrated ability to comprehend and give informed consent.
• Ability to complete patient diary.

Main Exclusion Criteria:

• Other clinically significant conditions apart from those typically associated with Parkinson's disease.
• Intake of medication associated with exacerbation of dyskinesia or with extrapyramidal side effects and tardive dyskinesia or induction of liver enzymes; neuroleptics; or specified drugs known to be substantially metabolized through the following cytochrome P450 isoenzymes: 1A2, 2B6, 2C19, 2C9, 2D6, and 2E1.
• Use of St. John's Wort or Ginkgo Biloba within 48 hrs prior to randomization and until the last treatment day with the study medication.
• Intake of an investigational drug within 30 days prior to initial screening.