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Efficacy, tolerability and safety of once-monthly administration of 75mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5mg once-daily dosage regimen.
Bone. 2014 Feb; 59:44-52.BONE

Abstract

Oral risedronate has been shown to be effective in the treatment of osteoporosis when administered once-daily or once-weekly in Japan. This randomized, double-blind, multicenter 12-month study was conducted to compare the efficacy and tolerability of oral risedronate 75mg once-monthly with 2.5mg once-daily in Japanese patients with involutional osteoporosis. Bone mineral density (BMD), biochemical markers of bone metabolism, fractures, and adverse events (AEs) were evaluated. At the end of the study (Month 12, last observation carried forward [M12, LOCF]), mean percent change (SD) from baseline in lumbar spine (L2-L4) BMD, measured by dual energy X-ray absorptiometry (primary endpoint), was increased by 5.69 (4.00)% in the 2.5mg once-daily group (n=428), and 5.98 (4.54)% in the 75mg once-monthly group (n=422). In the non-inferiority t-test (non-inferiority margin Δ=1.5%), the 75mg once-monthly group was non-inferior to the 2.5mg once-daily group (p<0.0001). The difference between treatment groups was 0.28% (95% CI, -0.31% to 0.88%). Changes in biochemical markers of bone metabolism were generally comparable in the two groups, although decreases in the percent change from baseline in urinary NTX/CRN and CTX/CRN were statistically greater in the 2.5mg once-daily group than the 75mg once-monthly group. The frequency of new vertebral fractures (including aggravation of prevalent fractures) at the end of the study (M12, LOCF) was also similar in the two groups: 1.2% in the 2.5mg once-daily group and 1.3% in the 75mg once-monthly group. The incidence of mild/moderate/severe AEs was 75.5%/6.3%/0.5% in the 2.5mg once-daily group and 77.7%/8.1%/0.7% in the 75mg once-monthly group. AEs associated with gastrointestinal symptoms occurred in approximately 30% of subjects in each group but with no severe cases. AEs potentially associated with acute phase reaction (including symptoms of influenza-like illness or pyrexia starting within 3days of the first dose of the study drug and with a duration of 7days or less) only occurred in the 75mg once-monthly group (2.1%, 9/422 subjects; influenza-like symptoms in 1 subject and pyrexia in 8 subjects), although the incidence was low without any severe cases. In conclusion, risedronate 75mg once-monthly (a dosage which is 30 times higher than risedronate 2.5mg once-daily) had non-inferior efficacy in terms of BMD and was similarly well tolerated compared to the once-daily regimen in Japanese patients with involutional osteoporosis. Consistent with the once-daily and once-weekly dosage, the once-monthly dosage of risedronate 75mg was half that used outside Japan (150mg).

Authors+Show Affiliations

School of Health Science and Rehabilitation Division, Tottori University, Nishicho 86, Yonago, Tottori, Japan. Electronic address: hagino@med.tottori-u.ac.jp.Department of Orthopedics, Nojima Hospital, Tottori, Japan.Clinical Development Dept., Ajinomoto Pharmaceuticals Company Limited, Tokyo, Japan.Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan.National Center for Global Health and Medicine, Tokyo, Japan.

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24184313

Citation

Hagino, Hiroshi, et al. "Efficacy, Tolerability and Safety of Once-monthly Administration of 75mg Risedronate in Japanese Patients With Involutional Osteoporosis: a Comparison With a 2.5mg Once-daily Dosage Regimen." Bone, vol. 59, 2014, pp. 44-52.
Hagino H, Kishimoto H, Ohishi H, et al. Efficacy, tolerability and safety of once-monthly administration of 75mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5mg once-daily dosage regimen. Bone. 2014;59:44-52.
Hagino, H., Kishimoto, H., Ohishi, H., Horii, S., & Nakamura, T. (2014). Efficacy, tolerability and safety of once-monthly administration of 75mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5mg once-daily dosage regimen. Bone, 59, 44-52. https://doi.org/10.1016/j.bone.2013.10.017
Hagino H, et al. Efficacy, Tolerability and Safety of Once-monthly Administration of 75mg Risedronate in Japanese Patients With Involutional Osteoporosis: a Comparison With a 2.5mg Once-daily Dosage Regimen. Bone. 2014;59:44-52. PubMed PMID: 24184313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy, tolerability and safety of once-monthly administration of 75mg risedronate in Japanese patients with involutional osteoporosis: a comparison with a 2.5mg once-daily dosage regimen. AU - Hagino,Hiroshi, AU - Kishimoto,Hideaki, AU - Ohishi,Hiroaki, AU - Horii,Sayako, AU - Nakamura,Toshitaka, Y1 - 2013/10/29/ PY - 2013/05/25/received PY - 2013/10/18/revised PY - 2013/10/23/accepted PY - 2013/11/5/entrez PY - 2013/11/5/pubmed PY - 2014/9/10/medline KW - Bisphosphonates KW - Bone mineral density KW - Involutional osteoporosis KW - Lumbar spine KW - Risedronate SP - 44 EP - 52 JF - Bone JO - Bone VL - 59 N2 - Oral risedronate has been shown to be effective in the treatment of osteoporosis when administered once-daily or once-weekly in Japan. This randomized, double-blind, multicenter 12-month study was conducted to compare the efficacy and tolerability of oral risedronate 75mg once-monthly with 2.5mg once-daily in Japanese patients with involutional osteoporosis. Bone mineral density (BMD), biochemical markers of bone metabolism, fractures, and adverse events (AEs) were evaluated. At the end of the study (Month 12, last observation carried forward [M12, LOCF]), mean percent change (SD) from baseline in lumbar spine (L2-L4) BMD, measured by dual energy X-ray absorptiometry (primary endpoint), was increased by 5.69 (4.00)% in the 2.5mg once-daily group (n=428), and 5.98 (4.54)% in the 75mg once-monthly group (n=422). In the non-inferiority t-test (non-inferiority margin Δ=1.5%), the 75mg once-monthly group was non-inferior to the 2.5mg once-daily group (p<0.0001). The difference between treatment groups was 0.28% (95% CI, -0.31% to 0.88%). Changes in biochemical markers of bone metabolism were generally comparable in the two groups, although decreases in the percent change from baseline in urinary NTX/CRN and CTX/CRN were statistically greater in the 2.5mg once-daily group than the 75mg once-monthly group. The frequency of new vertebral fractures (including aggravation of prevalent fractures) at the end of the study (M12, LOCF) was also similar in the two groups: 1.2% in the 2.5mg once-daily group and 1.3% in the 75mg once-monthly group. The incidence of mild/moderate/severe AEs was 75.5%/6.3%/0.5% in the 2.5mg once-daily group and 77.7%/8.1%/0.7% in the 75mg once-monthly group. AEs associated with gastrointestinal symptoms occurred in approximately 30% of subjects in each group but with no severe cases. AEs potentially associated with acute phase reaction (including symptoms of influenza-like illness or pyrexia starting within 3days of the first dose of the study drug and with a duration of 7days or less) only occurred in the 75mg once-monthly group (2.1%, 9/422 subjects; influenza-like symptoms in 1 subject and pyrexia in 8 subjects), although the incidence was low without any severe cases. In conclusion, risedronate 75mg once-monthly (a dosage which is 30 times higher than risedronate 2.5mg once-daily) had non-inferior efficacy in terms of BMD and was similarly well tolerated compared to the once-daily regimen in Japanese patients with involutional osteoporosis. Consistent with the once-daily and once-weekly dosage, the once-monthly dosage of risedronate 75mg was half that used outside Japan (150mg). SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/24184313/Efficacy_tolerability_and_safety_of_once_monthly_administration_of_75mg_risedronate_in_Japanese_patients_with_involutional_osteoporosis:_a_comparison_with_a_2_5mg_once_daily_dosage_regimen_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(13)00427-4 DB - PRIME DP - Unbound Medicine ER -