Editor's comment: Currently pregabalin, best known as Lyrica, is prescribed as a twice-a-day capsule. The clinical trial being reported here is for a controlled-release version of Lyrica that would only have to be taken once a day.
Once-daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a Phase III, double-blind, randomized withdrawal, placebo-controlled study.
Safety and efficacy of a once-daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design.
Research design and methods:
This multicenter study included 6-week single-blind pregabalin CR treatment followed by 13-week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ?50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330–495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep.
441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo.
The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p=0.02).
By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR.
Significantly more patients reported “benefit from treatment” (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant.
Most AEs were mild-to-moderate in severity (most frequent: dizziness, somnolence).
The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%).
Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well-tolerated in most patients. Generalizability may be limited by study duration and selective population.
Clinical Trial Registration: ClinicalTrials.gov NCT01271933
Source: Current Medical Research and Opinion
, May 27, 2014. By Lesley M. Arnold, Pierre Arsenault, Cynthia Huffman, Jeffrey L. Patrick, Michael Messig, Marci L. Chew, Luis Sanin, Joseph M. Scavone, Lynne Pauer and Andrew G. Clair.