title: 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.
  
  
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov 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.
authors.affiliation: University of Cincinnati College of Medicine , Cincinnati, OH , USA.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Arnold
authors.forename: Pierre
authors.initials: P
authors.lastname: Arsenault
authors.forename: Cynthia
authors.initials: C
authors.lastname: Huffman
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Patrick
authors.forename: Michael
authors.initials: M
authors.lastname: Messig
authors.forename: Marci L
authors.initials: ML
authors.lastname: Chew
authors.forename: Luis
authors.initials: L
authors.lastname: Sanin
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Scavone
authors.forename: Lynne
authors.initials: L
authors.lastname: Pauer
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clair
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004311:Double-Blind Method; D054796:Drug Dosage Calculations; D005260:Female; D005356:Fibromyalgia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D059408:Pain Management; D010147:Pain Measurement; D000069583:Pregabalin; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
keywords: Controlled-release; Fibromyalgia; Pain; Pregabalin; Randomized withdrawal; Sleep