Efficacy and safety of mirogabalin for the treatment of fibromyalgia: results from three 13-week randomized, double-blind, placebo- and active-controlled, parallel-group studies and a 52-week open-label extension study

Abstract

Objective: To investigate the efficacy and safety of mirogabalin, an α₂δ ligand, in patients with fibromyalgia (FM).

Methods: In three 13-week, multicenter, double-blind, phase 3 studies (studies A, B, and C), patients with FM (n = 1293, 1270, and 1301, respectively) were randomized (1:1:1:1) to placebo, pregabalin 150 mg twice daily, mirogabalin 15 mg once daily or mirogabalin 15 mg twice daily. The primary endpoint was the change in weekly average daily worst pain score (ADPS) at week 13. Key secondary endpoints included Patient Global Impression of Change and change in the Fibromyalgia Impact Questionnaire total score. Long-term safety of mirogabalin was assessed in a 52-week extension study.

Results: Neither mirogabalin dose demonstrated a significant ADPS reduction from baseline vs. placebo at week 13 in any of the three studies. Pregabalin significantly reduced ADPS from baseline vs. placebo in studies B and C (p = .0008 and .0001, respectively). The effect of mirogabalin compared with placebo on key secondary endpoints was variable across the studies. Mirogabalin was well tolerated by most patients in the phase 3 studies; no unexpected adverse events occurring during the 52-week extension study.

Conclusion: While both mirogabalin doses were well tolerated by most patients and showed potential for reducing pain associated with FM, the primary endpoint of significant pain reduction in patients on mirogabalin compared with placebo was not achieved in any of the three randomized controlled studies.

Clinical trial registration: NCT02146430; NCT02187159; NCT02187471; and NCT02234583 (extension study).

Keywords:

• Fibromyalgia
• pain
• mirogabalin
• pregabalin
• randomized controlled trial

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Transparency

Declaration of funding

This study was funded by Daiichi Sankyo Inc., Basking Ridge, NJ.

Author contributions

C.H., D.M., and D.J. designed the study. All authors participated in conducting the study and analyzing or interpreting the results. L.M.A., D.M., D.J., and S.W. drafted the manuscript. All authors provided critical review and revision of drafts, and approved the final version of the manuscript.

Declaration of financial/other relationships

L.M.A. has disclosed that she received funding for study conduct and also received research funding from Pfizer, Eli Lilly, Astellas, Teva, Allergan, Tonix, Cefaly, Aptinyx and Axsome; and consulting fees from Daiichi Sankyo Inc., Pfizer, Eli Lilly, IMC, Zynerba, Astellas, Cinrx, Prismic, Teva, and Allergan. C.H. has disclosed that he is employed by Daiichi Sankyo Inc. S.W., D.M., and D.J. have disclosed that they were employees of Daiichi Sankyo at the time the study was conducted. CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no relevant financial or other relationships to disclose.

Acknowledgements

The authors would like to acknowledge and thank all of the patients, investigators and study sites across the globe who participated in this large clinical program in fibromyalgia. Writing and editorial assistance was provided by Claire Daniele, PhD of AlphaBioCom LLC, King of Prussia, PA, and supported by Daiichi Sankyo Inc., Basking Ridge, NJ. Parts of this study were presented at 16th World Congress on Pain; 26–30 September 2016; Yokohama, Japan.