A randomized, double-blind, multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia

Abstract

IntroductionFibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan.MethodsThis randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life.ResultsA total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalin significantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events.ConclusionsThis trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalin is an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia.Trial RegistrationClinicalTrials.gov: NCT00830167

Efficacy and Safety of Pregabalin in Patients with Fibromyalgia and Comorbid Depression Taking Concurrent Antidepressant Medication: A Randomized, Placebo-controlled Study

“…Pregabalin improved diverse FM clinical domains, including severity of anxiety and depression, patient function and global status, and sleep behaviors, consistent with previous studies that used doses of 300 or 450 mg/day 10,12,13,14,16,24,27 . HADS-A and HADS-D scores significantly improved with pregabalin treatment versus placebo.…”

“…In our study, the treatment difference was similar to that seen in 5 pivotal studies in patients with FM not receiving concurrent antidepressant medication 10,12,13,14,24 . In those studies, the difference in mean pain score between pregabalin (300 or 450 mg/day) and placebo ranged from -0.33 to -0.98, compared with -0.61 in this study.…”

“…The discontinu-ation rate owing to AE was similar to that seen in previous studies and the safety profile of pregabalin was consistent with previous studies in patients not taking concurrent antidepressant medication 10,12,13,14,24 . The discontinu-ation rate owing to AE was similar to that seen in previous studies and the safety profile of pregabalin was consistent with previous studies in patients not taking concurrent antidepressant medication 10,12,13,14,24 .…”

Alternatives to Opioids in the Pharmacologic Management of Chronic Pain Syndromes: A Narrative Review of Randomized, Controlled, and Blinded Clinical Trials

“…Crofford et al found that only 450 mg/day dosing was superior to placebo for pain efficacy (not at 150 or 300 mg/day) 113 . At doses of 300 or 450 mg/day, Ohta et al reported superior efficacy of pregabalin over placebo 114 . Arnold et al 115 and Clair 116 et al also reported superior efficacy of pregabalin in pooled groups of pregabalin doses (300–450 mg/day) over placebo.…”

Effect of different doses of pregabalin on skeletal muscle ischaemia-reperfusion injury in rats

“…Currently, pregabalin is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy (8,9), postherpetic neuralgia (10,11), and management of fi bromyalgia (12,13). In addition, pregabalin is used frequently in the treatment of anxiety (14).…”