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An open-label long-term phase III extension trial to evaluate the safety and efficacy of pregabalin in Japanese patients with fibromyalgia

  • Original Article
  • Published:
Modern Rheumatology

Abstract

Objectives

To assess the long-term safety and efficacy of pregabalin for the treatment of Japanese patients with fibromyalgia (FM).

Methods

This 53-week, open-label extension study was conducted at 20 study sites in Japan in patients with FM who had completed a preceding 16-week, placebo-controlled, double-blind trial. Patients received pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day. The primary endpoint was safety, and secondary endpoints included measures of pain, sleep, and physical functioning.

Results

106 patients entered the trial and received at least one dose of the study drug. The most common treatment-related adverse events were somnolence, dizziness, increased weight, and constipation. There were no treatment-related serious or severe adverse events. There were five (4.7 %) discontinuations due to adverse events, of which three (2.8 %) were considered related to the study drug. Most adverse events resolved over time and could be managed without dose reduction or treatment discontinuation. Improvements in secondary efficacy endpoints of pain, sleep, and physical functioning emerged early in the study and were maintained for the duration of treatment.

Conclusions

These data indicate that the long-term treatment of Japanese FM patients with pregabalin may be both safe and effective.

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References

  1. Ablin JN, Cohen H, Buskila D. Mechanisms of disease: genetics of fibromyalgia. Nat Clin Pract Rheumatol. 2006;2(12):671–8.

    Article  PubMed  CAS  Google Scholar 

  2. Bradley LA. Pathophysiology of fibromyalgia. Am J Med. 2009;122(12 suppl):S22–30.

    Article  PubMed  Google Scholar 

  3. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthr Rheum. 1990;33(2):160–72.

    Article  CAS  Google Scholar 

  4. Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthr Care Res (Hoboken). 2010;62(5):600–10.

    Article  Google Scholar 

  5. Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, Kanazawa T, et al. The Japanese version of the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and the fibromyalgia symptom scale: reliability and validity. Mod Rheumatol. 2012;22(1):40–4.

    Article  PubMed  Google Scholar 

  6. Hoffman DL, Dukes EM. The health status burden of people with fibromyalgia: a review of studies that assessed health status with the SF-36 or the SF-12. Int J Clin Pract. 2008;62(1):115–26.

    Article  PubMed  CAS  Google Scholar 

  7. Schaefer C, Chandran A, Hufstader M, Baik R, McNett M, Goldenberg D, et al. The comparative burden of mild, moderate and severe fibromyalgia: results from a cross-sectional survey in the United States. Health Qual Life Outcomes. 2011;9:71.

    Article  PubMed  Google Scholar 

  8. Winkelmann A, Perrot S, Schaefer C, Ryan K, Chandran A, Sadosky A, et al. Impact of fibromyalgia severity on health economic costs: results from a European cross-sectional study. Appl Health Econ Health Policy. 2011;9(2):125–36.

    Article  PubMed  Google Scholar 

  9. Matsumoto M. Epidemiology of fibromyalgia [in Japanese]. Pharma Medica. 2006;24(6):35–9.

    Google Scholar 

  10. Nishioka K. Research platform for fibromyalgia in Japan. Arthr Res Ther. 2012;14(suppl 1):O5.

    Article  Google Scholar 

  11. Mease PJ, Clauw DJ, Arnold LM, Goldenberg DL, Witter J, Williams DA, et al. Fibromyalgia syndrome. J Rheumatol. 2005;32(11):2270–7.

    PubMed  Google Scholar 

  12. Bennett RM. Emerging concepts in the neurobiology of chronic pain: evidence of abnormal sensory processing in fibromyalgia. Mayo Clin Proc. 1999;74(4):385–98.

    Article  PubMed  CAS  Google Scholar 

  13. Field MJ, Cox PJ, Stott E, Melrose H, Offord J, Su TZ, et al. Identification of the α2-δ-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci USA. 2006;103(46):17537–42.

    Article  PubMed  CAS  Google Scholar 

  14. Arnold LM, Russell IJ, Diri EW, Duan WR, Young JP Jr, Sharma U, et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain. 2008;9(9):792–805.

    Article  PubMed  CAS  Google Scholar 

  15. Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE, et al. Pregabalin 1008–105 Study Group. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthr Rheum. 2005;52(4):1264–73.

    Article  CAS  Google Scholar 

  16. Mease PJ, Russell IJ, Arnold LM, Florian H, Young JP Jr, Martin SA, et al. A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol. 2008;35(3):502–14.

    PubMed  CAS  Google Scholar 

  17. Pauer L, Winkelmann A, Arsenault P, Jespersen A, Whelan L, Atkinson G, A0081100 Investigators, et al. An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia. J Rheumatol. 2011;38(12):2643–52.

    Article  PubMed  CAS  Google Scholar 

  18. Ohta H, Oka H, Usui C, Ohkura M, Suzuki M, Nishioka K. A randomized, double-blind, multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia. Arthr Res Ther. 2012;14(5):R217.

    Article  CAS  Google Scholar 

  19. Hays RD, Stewart AL. Sleep measures. In: Stewart AL, Ware Jr JE, editors. Measuring functioning and well-being. Durham: Duke University Press; 1992. p. 235–9.

    Google Scholar 

  20. Burckhardt CS, Clark SR, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol. 1991;18(5):728–33.

    PubMed  CAS  Google Scholar 

  21. Osada K, Oka H, Isomura T, Nakamura I, Tominaga K, Takahashi S, et al. Development of the Japanese version of the Fibromyalgia Impact Questionnaire (JFIQ): psychometric assessments of reliability and validity. Int J Rheum Dis. 2011;14(1):74–80.

    Article  PubMed  Google Scholar 

  22. Crofford LJ, Mease PJ, Simpson SL, Young JP Jr, Martin SA, Haig GM, et al. Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. Pain. 2008;136(3):419–31.

    Article  PubMed  CAS  Google Scholar 

  23. Satoh J, Yagihashi S, Baba M, Suzuki M, Arakawa A, Yoshiyama T. Efficacy and safety evaluation of pregabalin treatment over 52 weeks in patients with diabetic neuropathic pain extended after a double-blind placebo-controlled trial. J Diabetes Investig. 2011;2(6):457–63.

    Article  CAS  Google Scholar 

  24. Satoh J, Yagihashi S, Baba M, Suzuki M, Arakawa A, Yoshiyama T, et al. Efficacy and safety of pregabalin for treating neuropathic pain associated with diabetic peripheral neuropathy: a 14 week, randomized, double-blind, placebo-controlled trial. Diabet Med. 2011;28(1):109–16.

    Article  PubMed  CAS  Google Scholar 

  25. Ogawa S, Suzuki M, Arakawa A, Yoshiyama T. Long-term efficacy and safety of pregabalin in patients with postherpetic neuralgia: results of a 52-week, open-label, flexible-dose study [in Japanese]. Masui. 2010;59(8):961–70.

    PubMed  Google Scholar 

  26. Ogawa S, Satoh J, Arakawa A, Yoshiyama T, Suzuki M. Pregabalin treatment for peripheral neuropathic pain—a review of safety data from randomized controlled trials conducted in Japan and in the West. Drug Saf. 2012;35(10):793–806.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was funded by Pfizer Japan Inc. Medical writing support was provided by Joshua Fink PhD, of UBC Scientific Solutions, and funded by Pfizer Inc. We would like to acknowledge the contribution of the study’s principal investigators: Sadahiko Kameda (Kameda Internal Medicine), Yoshinobu Koyama (Aso Iizuka Hospital), Yoshifuji Matsumoto (Fujita Health University Nanakuri Sanatorium), Kenji Miki (Kobe Konan Yamate Clinic), Yasuhiko Munakata (Taihaku Sakura Hospital), Masato Murakami (Nihon University Itabashi Hospital), Shouhei Nagaoka (Yokohama Minami Kyosai Hospital), Shiro Nakayama (Nakayama Internal Rheumatism Allergic), Syuji Ohno (Ohno Clinic), Hiroshi Oka (Kasumigaseki Aban Clinic), Yoshinori Okubo (Okubo Clinic), Masanari Omata (Ohimachi Orthopaedic Clinic), Motohiro Oribe (Oribe Rheumatism Internist Clinic), Yuki Sekiguchi (Yokohama Motomachi Women’s Clinic LUNA), Eishi Shirasawa (Shirasawa Orthopedic Clinic), Takao Sugiyama (Shimoshizu National Hospital), Nobuo Takubo (Takubo Rheumatism Orthopedics Department), Fusazo Urano (Shinonoi General Hospital), Ryoichi Yamazaki (Yamazaki Orthopedic Clinic), and Masao Yukioka (Yukioka Hospital).

Conflict of interest

H. Ohta, M.O., and M.S. are employees of Pfizer Japan Inc. K.N. and H. Oka received a consultancy fee from Pfizer Japan Inc. for their participation in this study. C.U. declares no competing interests. K.N., H. Oka, and C.U. were not compensated for their work on this manuscript.

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Authors and Affiliations

  1. Pfizer Japan Inc., 3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan

    Hiroyoshi Ohta, Masayuki Ohkura & Makoto Suzuki

  2. Rheumatic Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan

    Hiroshi Oka

  3. Department of Psychiatry, Juntendo University School of Medicine, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521, Japan

    Chie Usui

  4. Institute of Innovative Medical Science and Education, Tokyo Medical University, 6-1-1 Shinjyuku, Shinjyuku-ku, Tokyo, 160-8402, Japan

    Kusuki Nishioka

Authors
  1. Hiroyoshi Ohta
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  2. Hiroshi Oka
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  3. Chie Usui
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  4. Masayuki Ohkura
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  5. Makoto Suzuki
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  6. Kusuki Nishioka
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Corresponding author

Correspondence to Kusuki Nishioka.

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Ohta, H., Oka, H., Usui, C. et al. An open-label long-term phase III extension trial to evaluate the safety and efficacy of pregabalin in Japanese patients with fibromyalgia. Mod Rheumatol 23, 1108–1115 (2013). https://doi.org/10.1007/s10165-012-0803-x

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  • DOI: https://doi.org/10.1007/s10165-012-0803-x

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