Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study

Abstract

Objective:

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.

Clinical trial registration:

ClinicalTrials.gov identifier: NCT01271933.

Results:

A total of 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%).

Conclusions:

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.

Keywords::

• Controlled-release
• Fibromyalgia
• Pain
• Pregabalin
• Randomized withdrawal
• Sleep

View correction statement:

Corrections to: Once-daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study

Transparency

Declaration of funding

The study was sponsored by Pfizer Inc.

Declaration of financial/other relationships

L.M.A. has disclosed that she has received research support from Eli Lilly and Company, Pfizer, Forest, Theravance, Takeda, AstraZeneca, and Tonix; served as a consultant for Pfizer, Daiichi Sankyo, Theravance, Purdue, and Shire; and participated on a speakers bureau for Pfizer. P.A. has disclosed that he has served as a member of an advisory board for Pfizer Canada and AstraZeneca, and as a speaker for Pfizer, Eli Lilly and Company, Valeant, Purdue, and Janssen in Canada. C.H. has disclosed that she has received research funding from Meridien Research and has participated on a fibromyalgia advisory board for Pfizer. J.L.P., M.M., M.L.C., L.S., J.M.S., L.P., and A.G.C. have disclosed that they are full-time employees of Pfizer Inc and receive salary and other compensation, including stock options.

CMRO peer reviewers on this manuscript have no relevant financial relationships to disclose.

Acknowledgments

Medical writing support was provided by Diane Hoffman PhD of Engage Scientific Solutions and funded by Pfizer Inc.

Previous presentation: These data were presented at the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Scientific Meeting, 25–30 October, 2013.