Safety and efficacy of esreboxetine in patients with fibromyalgia: A fourteen-week, randomized, double-blind, placebo-controlled, multicenter clinical trial

Authors

  • Lesley M. Arnold,

    Corresponding author
    1. University of Cincinnati College of Medicine, Cincinnati, Ohio
    • Psychiatry and Behavioral Neuroscience, Women's Health Research Program, University of Cincinnati Medical Arts Building, 222 Piedmont Avenue, Suite 8200, Cincinnati, OH 45219
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    • Dr. Arnold has received consulting fees from Eli Lilly, Cypress Bioscience, Forest Laboratories, Takeda, AstraZeneca, Sanofi-Aventis, Grünenthal, Johnson & Johnson, and Daiichi Sankyo (less than $10,000 each) and from Pfizer (more than $10,000); she has received research grants from Eli Lilly, Pfizer, Cypress Bioscience, Boehringer Ingelheim, Forest Laboratories, Novartis, and Takeda.

  • Ian Hirsch,

    1. Pfizer Global Research and Development, Sandwich, UK
    Current affiliation:
    1. AstraZeneca, Cheshire, UK
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    • Dr. Hirsch owns stock or stock options in AstraZeneca.

  • Paul Sanders,

    1. Pfizer Global Research and Development, Sandwich, UK
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    • Dr. Sanders owns stock or stock options in Pfizer and AstraZeneca.

  • Amanda Ellis,

    1. Pfizer Global Research and Development, Sandwich, UK
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    • Drs. Ellis and Hughes own stock or stock options in Pfizer.

  • Bernadette Hughes

    1. Pfizer Global Research and Development, Sandwich, UK
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    • Drs. Ellis and Hughes own stock or stock options in Pfizer.


  • ClinicalTrials.gov identifier: NCT00612170.

Abstract

Objective

To evaluate the efficacy, tolerability, and safety of multiple fixed dosages of esreboxetine for the treatment of fibromyalgia.

Methods

Patients meeting the American College of Rheumatology criteria for fibromyalgia were randomized to receive esreboxetine at dosages of 4 mg/day (n = 277), 8 mg/day (n = 284), or 10 mg/day (n = 283) or matching placebo (n = 278) for 14 weeks. The primary efficacy outcomes were the weekly mean pain score and the Fibromyalgia Impact Questionnaire (FIQ) total score at week 14. Secondary efficacy measures included scores for the Patient's Global Impression of Change (PGIC) scale, the Global Fatigue Index (GFI), and the 36-item Short-Form health survey (SF-36; physical function scale only) at week 14. The safety profile of esreboxetine was evaluated based on adverse events and other safety measures.

Results

Patients receiving all dosages of esreboxetine demonstrated statistically significant improvements in the pain score (P ≤ 0.025), the FIQ score (P ≤ 0.023), and the PGIC score (P ≤ 0.007) compared with patients in the placebo group. Additionally, patients receiving esreboxetine at dosages of 4 mg/day and 8 mg/day showed statistically significant improvements in the GFI score compared with those receiving placebo (P = 0.001). No significant differences in SF-36 physical function scores were observed between patients receiving esreboxetine (any dosage) and those receiving placebo. Adverse events were mostly mild to moderate in severity; insomnia, constipation, dry mouth, nausea, dizziness, hot flush, headache, hyperhidrosis, and palpitations were reported most frequently.

Conclusion

Esreboxetine was generally well tolerated and was associated with significant improvements in pain, FIQ, PGIC, and fatigue scores compared with placebo. The lack of a dose-response relationship in both the efficacy and safety analyses suggests that esreboxetine at a dosage of 4 mg/day would offer clinical benefit with the least risk of drug exposure.

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