Title: Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations

Authors: Lees, AJ MD; Ferreira, J MD; Rascol, O, MD; et al


What You Need to Know:

In Parkinson’s disease (PD) patients treated with levodopa, a significant reduction in mean daily off-time and motor fluctuations was seen with a 50mg/day dose of  opicapone, a catechol o-methyltransferase (COMT) inhibitor designed to provide effectiveness without the common side effects seen with other COMT inhibitors (ie, hepatotoxicity). This effect was sustained for at least one year.

Trial Design:

  • Phase 3 international, multicenter, randomized, double-blind, placebo-controlled outpatient study (14-15 weeks); patients received either opicapone 25mg/day, 50mg/day, or placebo.
  • A 1-year open-label phase followed where patients received active treatment
  • To be enrolled, PD patients had to experience signs of end-of-dose deterioration; mean total awake off-time of at least 1.5 hours (not including AM akinesia)
  • Study period: March 2011 to June 2013; data analyzed from July 2013 to July 2014 (evaluable population)
  • 427 patients (258 men, 169 women); 25mg/day (n=129), 50mg/day (n=154), placebo (n=144)
  • 376 finished double-blind phase and entered open-label phase; 286 patients completed 1 year open-label phase

Key Outcomes:

  • Least squares mean change in off-time (at the end of double-blind phase): 25mg/day: –101.7 (14.9) minutes; 50mg/day: –118.8 (13.8) minutes; placebo: –64.5 (14.4) minutes
  • Adjusted treatment difference vs. placebo significant for 50mg/day group (treatment effect, −54.3 [95% CI, −96.2 to −12.4] minutes; P = 0.008), but not 25mg/day group (treatment effect, −37.2 [95% CI, −80.8 to 6.4] minutes; P = 0.11).
  • Off-time reduction sustained through open-label phase  (−126.3 minutes at 1-year open-label end point)
  • Common adverse events: dyskinesia, constipation, dry mouth