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Phase II/III, randomized, double-blind, parallel-group study of monthly delayed-release versus daily immediate-release risedronate tablets in Japanese patients with involutional osteoporosis

  • Satoshi SoenEmail author
  • Hideaki Kishimoto
  • Hiroshi Hagino
  • Teruki Sone
  • Hiroaki Ohishi
  • Tsukasa Fujimoto
  • Emma Sasaki
  • Sakae Tanaka
  • Toshitsugu Sugimoto
Original Article
  • 6 Downloads

Abstract

Absorption of oral immediate-release (IR) risedronate tablets is reduced by food intake, thus a delayed-release (DR) tablet has been developed to overcome the necessity of taking IR tablets under fasting conditions. This randomized, double-blind, phase II/III study compared efficacy and safety of risedronate IR once-daily (QD) and DR once-monthly (QM) tablets in Japanese patients with involutional osteoporosis. Patients received 2.5 mg IR on awakening QD, or 25 or 37.5 mg DR on awakening, following breakfast, or 30 min after breakfast, QM for 12 months. Primary endpoint was non-inferiority in mean percent change from baseline to end of study (month 12, last observation carried forward [M12, LOCF]) in mean lumbar spine (L2–L4) bone mineral density (BMD) between risedronate IR on awakening and DR following breakfast. Mean percent changes in (L2–L4) BMD at M12, LOCF were 5.07% (IR at awakening, n = 190), 3.36% (25 mg DR following breakfast, n = 194), and 4.11% (37.5 mg DR following breakfast, n = 181). Mean percent change in (L2–L4) BMD was numerically lower in the DR following breakfast groups versus the respective on awakening and 30 min after breakfast DR groups. Overall incidences of treatment-emergent adverse events (TEAEs) were comparable between groups. In the DR groups, 1.5–4.0% of patients reported TEAEs potentially associated with acute-phase reactions versus 0% in the IR group. In this study, non-inferiority could not be declared for 37.5 or 25 mg DR following breakfast QM (p = 0.1346 or p = 0.6711, respectively) versus 2.5 mg IR on awakening QD.

Keywords

Osteoporosis Risedronate Delayed release Immediate release Japan 

Notes

Acknowledgments

This study was supported by the Joint Development Program of EA Pharma Co., Ltd., and Takeda Pharmaceutical Company Ltd. The authors thank all the patients who participated in these studies and their families, as well as the investigators and site staff who made these studies possible. Writing support was provided by Matthew Hallam and Stephen Hill of FireKite, an Ashfield company, part of UDG Healthcare plc, during the development of this manuscript, which was funded by Takeda Pharmaceutical Company Ltd., in compliance with Good Publication Practice 3 ethical guidelines (Battisti et al., Ann Intern Med 2015;163:461–4). This trial was funded by EA Pharma Co., Ltd. (Tokyo, Japan), and Takeda Pharmaceutical Company Limited (Osaka, Japan). JapicCTI-142439 (registered by EA Pharma); JapicCTI-142440 (registered by Takeda).

Compliance with ethical standards

Conflict of interest

S.S. has received grants/research support from Daiichi-Sankyo, Eisai, and Takeda; and is a member of speaker’s bureaus for Asahi Kasei, Astellas Pharma, Chugai, Daiichi-Sankyo, Eisai, Merck Sharp & Dohme, Ono, Pfizer, Takeda, and Teijin Pharma. H.K. has received consulting fees from Asahi Kasei Pharma, Daiichi-Sankyo, Chugai Pharmaceutical, and Eli Lilly Japan. H.H. has received grants/research support or lecture fees from Asahi Kasei Pharma, Astellas Pharma, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan, Mitsubishi Tanabe, Merck Sharp & Dohme, Ono, Pfizer, Taisho Toyama Pharmaceutical, Takeda, and Teijin Pharma. T.So. has received research grants from Asahi Kasei Pharma, Astellas Pharma, Daiichi-Sankyo, Pfizer, Taisho Toyama Pharmaceutical, Takeda, and Teijin Pharma; and has received consulting fees from Daiichi-Sankyo and Takeda. H.O. is an employee of EA Pharma. T.F. and E.S. are employees of Takeda Pharmaceutical. S.T. has been a consultant and received honoraria from Eisai, given expert testimony for Takeda Pharmaceutical and EA Pharma, undertaken contracted research for EA Pharma, and received endowments from Takeda Pharmaceutical. T.Su. has received research grants from Astellas Pharma, Eisai, Daiichi-Sankyo, Chugai Pharmaceutical, and Eli Lilly Japan as well as consulting and/or lecture fees from Asahi Kasei Pharma and Daiichi-Sankyo.

Ethics statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients provided written, informed consent. Trial registration: ClinicalTrials.gov number NCT02063854.

Supplementary material

774_2019_1031_MOESM1_ESM.docx (57 kb)
Supplementary material 1 (DOCX 57 kb)

References

  1. 1.
    Das S, Crockett JC (2013) Osteoporosis—a current view of pharmacological prevention and treatment. Drug Des Dev Ther 7:435–448Google Scholar
  2. 2.
    Crandall CJ, Newberry SJ, Diamant A, Lim YW, Gellad WF, Booth MJ, Motala A, Shekelle PG (2014) Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review. Ann Intern Med 161:711–723CrossRefGoogle Scholar
  3. 3.
    Goldshtein I, Rouach V, Shamir-Stein N, Yu J, Chodick G (2016) Role of side effects, physician involvement, and patient perception in non-adherence with oral bisphosphonates. Adv Ther 33:1374–1384CrossRefGoogle Scholar
  4. 4.
    Mitchell DY, Heise MA, Pallone KA, Clay ME, Nesbitt JD, Russell DA, Melson CW (1999) The effect of dosing regimen on the pharmacokinetics of risedronate. Br J Clin Pharmacol 48:536–542CrossRefGoogle Scholar
  5. 5.
    Warner Chilcott Company LLC (2015) ACTONEL® (risedronate sodium) tablets, United States prescribing information. http://www.allergan.com/assets/pdf/actonel_pi
  6. 6.
    Kendler D, Kung AW, Fuleihan G, Gonzalez Gonzalez JG, Gaines KA, Verbruggen N, Melton ME (2004) Patients with osteoporosis prefer once weekly to once daily dosing with alendronate. Maturitas 48:243–251CrossRefGoogle Scholar
  7. 7.
    Kishimoto H, Maehara M (2015) Compliance and persistence with daily, weekly, and monthly bisphosphonates for osteoporosis in Japan: analysis of data from the CISA. Arch Osteoporos 10:231CrossRefGoogle Scholar
  8. 8.
    Simon JA, Lewiecki EM, Smith ME, Petruschke RA, Wang L, Palmisano JJ (2002) Patient preference for once-weekly alendronate 70 mg versus once-daily alendronate 10 mg: a multicenter, randomized, open-label, crossover study. Clin Ther 24:1871–1886CrossRefGoogle Scholar
  9. 9.
    Agrawal S, Krueger DC, Engelke JA, Nest LJ, Krause PF, Drinka PJ, Binkley NC (2006) Between-meal risedronate does not alter bone turnover in nursing home residents. J Am Geriatr Soc 54:790–795CrossRefGoogle Scholar
  10. 10.
    Kendler DL, Ringe JD, Ste-Marie LG, Vrijens B, Taylor EB, Delmas PD (2009) Risedronate dosing before breakfast compared with dosing later in the day in women with postmenopausal osteoporosis. Osteoporos Int 20:1895–1902CrossRefGoogle Scholar
  11. 11.
    Ogura Y, Gonsho A, Cyong JC, Orimo H (2004) Clinical trial of risedronate in Japanese volunteers: a study on the effects of timing of dosing on absorption. J Bone Miner Metab 22:120–126CrossRefGoogle Scholar
  12. 12.
    Kinov P, Boyanov M (2012) Clinical utility of risedronate in postmenopausal osteoporosis: patient considerations with delayed-release formulation. Int J Womens Health 4:167–174CrossRefGoogle Scholar
  13. 13.
    Papaioannou A, Kennedy CC, Dolovich L, Lau E, Adachi JD (2007) Patient adherence to osteoporosis medications: problems, consequences and management strategies. Drugs Aging 24:37–55CrossRefGoogle Scholar
  14. 14.
    Pazianas M, Abrahamsen B, Ferrari S, Russell RG (2013) Eliminating the need for fasting with oral administration of bisphosphonates. Ther Clin Risk Manag 9:395–402CrossRefGoogle Scholar
  15. 15.
    McClung MR, Miller PD, Brown JP, Zanchetta J, Bolognese MA, Benhamou CL, Balske A, Burgio DE, Sarley J, McCullough LK, Recker RR (2012) Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet. Osteoporos Int 23:267–276CrossRefGoogle Scholar
  16. 16.
    McClung MR, Balske A, Burgio DE, Wenderoth D, Recker RR (2013) Treatment of postmenopausal osteoporosis with delayed-release risedronate 35 mg weekly for 2 years. Osteoporos Int 24:301–310CrossRefGoogle Scholar
  17. 17.
    Warner Chilcott Company LLC (2015) ATELVIA® (risedronate sodium) delayed-release tablets, United States prescribing information. http://www.allergan.com/assets/pdf/atelvia_pi
  18. 18.
    Takeda Japan (2017) Phase 1 CPH-401 study, unpublished resultsGoogle Scholar
  19. 19.
    Soen S, Fukunaga M, Sugimoto T, Sone T, Fujiwara S, Endo N, Gorai I, Shiraki M, Hagino H, Hosoi T, Ohta H, Yoneda T, Tomomitsu T (2013) Diagnostic criteria for primary osteoporosis: year 2012 revision. J Bone Miner Metab 31:247–257CrossRefGoogle Scholar
  20. 20.
    Hagino H, Kishimoto H, Ohishi H, Horii S, Nakamura T (2014) Efficacy, tolerability and safety of once-monthly administration of 75 mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5 mg once-daily dosage regimen. Bone 59:44–52CrossRefGoogle Scholar
  21. 21.
    Blouin J, Dragomir A, Moride Y, Ste-Marie LG, Fernandes JC, Perreault S (2008) Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women. Br J Clin Pharmacol 66:117–127CrossRefGoogle Scholar
  22. 22.
    Mikyas Y, Agodoa I, Yurgin N (2014) A systematic review of osteoporosis medication adherence and osteoporosis-related fracture costs in men. Appl Health Econ Health Policy 12:267–277CrossRefGoogle Scholar
  23. 23.
    Silverman SL, Schousboe JT, Gold DT (2011) Oral bisphosphonate compliance and persistence: a matter of choice? Osteoporos Int 22:21–26CrossRefGoogle Scholar
  24. 24.
    Chodick G, Moser SS, Goldshtein I (2016) Non-adherence with bisphosphonates among patients with osteoporosis: impact on fracture risk and healthcare cost. Expert Rev Pharmacoecon Outcomes Res 16:359–370CrossRefGoogle Scholar
  25. 25.
    Bock O, Felsenberg D (2008) Bisphosphonates in the management of postmenopausal osteoporosis–optimizing efficacy in clinical practice. Clin Interv Aging 3:279–297CrossRefGoogle Scholar
  26. 26.
    Hadji P, Claus V, Ziller V, Intorcia M, Kostev K, Steinle T (2012) GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates. Osteoporos Int 23:223–231CrossRefGoogle Scholar
  27. 27.
    Fukunaga M, Kushida K, Kishimoto H, Shiraki M, Taketani Y, Minaguchi H, Inoue T, Morita R, Morii H, Yamamoto K, Ohashi Y, Orimo H (2002) A comparison of the effect of risedronate and etidronate on lumbar bone mineral density in Japanese patients with osteoporosis: a randomized controlled trial. Osteoporos Int 13:971–979CrossRefGoogle Scholar
  28. 28.
    Kishimoto H, Fukunaga M, Kushida K, Shiraki M, Itabashi A, Nawata H, Nakamura T, Ohta H, Takaoka K, Ohashi Y (2006) Efficacy and tolerability of once-weekly administration of 17.5 mg risedronate in Japanese patients with involutional osteoporosis: a comparison with 2.5-mg once-daily dosage regimen. J Bone Miner Metab 24:405–413CrossRefGoogle Scholar
  29. 29.
    Ogura Y, Gonsho A, Cyong JC, Orimo H (2004) Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies. J Bone Miner Metab 22:111–119CrossRefGoogle Scholar
  30. 30.
    Divittorio G, Jackson KL, Chindalore VL, Welker W, Walker JB (2006) Examining the relationship between bone mineral density and fracture risk reduction during pharmacologic treatment of osteoporosis. Pharmacotherapy 26:104–114CrossRefGoogle Scholar
  31. 31.
    US Food and Drug Administration Center for Drug Evaluation and Research (2010) Risedronate sodium—clinical pharmacology and biopharmaceutics reviews (application number: 022560Orig1s000). http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022560orig1s000clinpharmr.pdf
  32. 32.
    Kennel KA, Drake MT (2009) Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc 84:632–637CrossRefGoogle Scholar
  33. 33.
    Sieber P, Lardelli P, Kraenzlin CA, Kraenzlin ME, Meier C (2013) Intravenous bisphosphonates for postmenopausal osteoporosis: safety profiles of zoledronic acid and ibandronate in clinical practice. Clin Drug Investig 33:117–122CrossRefGoogle Scholar
  34. 34.
    Strampel W, Emkey R, Civitelli R (2007) Safety considerations with bisphosphonates for the treatment of osteoporosis. Drug Saf 30:755–763CrossRefGoogle Scholar
  35. 35.
    Nakamura T, Ito M, Hashimoto J, Shinomiya K, Asao Y, Katsumata K, Hagino H, Inoue T, Nakano T, Mizunuma H (2015) Clinical efficacy and safety of monthly oral ibandronate 100 mg versus monthly intravenous ibandronate 1 mg in Japanese patients with primary osteoporosis. Osteoporos Int 26:2685–2693CrossRefGoogle Scholar
  36. 36.
    Miller PD, McClung MR, Macovei L, Stakkestad JA, Luckey M, Bonvoisin B, Reginster JY, Recker RR, Hughes C, Lewiecki EM, Felsenberg D, Delmas PD, Kendler DL, Bolognese MA, Mairon N, Cooper C (2005) Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res 20:1315–1322CrossRefGoogle Scholar

Copyright information

© The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Satoshi Soen
    • 1
    Email author
  • Hideaki Kishimoto
    • 2
  • Hiroshi Hagino
    • 3
  • Teruki Sone
    • 4
  • Hiroaki Ohishi
    • 5
  • Tsukasa Fujimoto
    • 6
  • Emma Sasaki
    • 6
  • Sakae Tanaka
    • 7
  • Toshitsugu Sugimoto
    • 8
  1. 1.Department of Orthopedic Surgery and RheumatologyKindai University Nara HospitalIkomaJapan
  2. 2.Department of Orthopedic SurgeryNojima HospitalTottoriJapan
  3. 3.School of Health Science and Rehabilitation DivisionTottori UniversityYonagoJapan
  4. 4.Department of Nuclear MedicineKawasaki Medical SchoolKurashikiJapan
  5. 5.EA Pharma Co., Ltd.TokyoJapan
  6. 6.Takeda Pharmaceutical Company Ltd.OsakaJapan
  7. 7.Orthopedic Surgery, Sensory and Motor System Medicine, Surgical Sciences, Graduate School of MedicineThe University of TokyoTokyoJapan
  8. 8.Internal Medicine 1, Shimane University, Faculty of MedicineIzumoJapan

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