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.


Continue Reading

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