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Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-controlled, dose-ranging study.
Clin Ther. 2009 Feb; 31(2):272-85.CT

Abstract

BACKGROUND

Risedronate 5 mg/d is approved by the US Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. Once-monthly dosing options might increase treatment compliance and persistence.

OBJECTIVE

The aim of this study was to compare the tolerability and efficacy of 3 once-monthly risedronate dosing regimens with those of risedronate 5 mg/d.

METHODS

This Phase II, 6-month, randomized, double-blind, active-controlled, dose-ranging study was conducted at 13 clinical research centers and hospitals in Croatia, Poland, Canada, and the United States between April 2004 and June 2005. Post-menopausal women aged 50 to 85 years with a lumbar spine T-score <-2.0 were randomly assigned to 1 of 4 treatment groups: risedronate 100, 150, or 200 mg/mo or 5 mg/d (active control), administered PO for 6 months. Evaluation of tolerability, the primary study objective, was based on adverse-event (AE) profiles and clinical laboratory values. Efficacy evaluation, a secondary objective, was a noninferiority comparison of the changes from baseline in bone mineral density (BMD) and bone turnover markers (BTMs).

RESULTS

Of 370 patients randomized (91, 88, 88, and 103 patients in the risedronate 100-, 150-, and 200-mg/mo and 5-mg/d groups, respectively), 57% were > or =65 years of age and 99% were white; 316 patients (85.4%) completed the study. Completion rates were not significantly different across treatment groups, nor were reasons for discontinuation. Between-group differences in the incidences of treatment-emergent AEs, serious AEs, and upper gastrointestinal (GI) AEs were nonsignificant. Overall, 6 (7%), 14 (16%), 6 (7%), and 9 patients (9%) withdrew because of AEs in the 100-, 150-, and 200-mg/mo and 5 mg/d groups, respectively. GI disorders were the AEs that most frequently led to study withdrawal (5 [5.5%], 7 [8.0%], 4 [4.5%], and 6 [5.8%]). No trends were observed in the nature or frequency of other AEs causing withdrawal. All serious AEs were considered unrelated to treatment, with the exception of erosive esophagitis in 1 patient (1%) who received the 5-mg/d dose. Mean percentage increases in BMD were 2.10%, 2.99%, and 3.38% with risedronate 100, 150, and 200 mg/mo, respectively, versus 3.05% with 5 mg/d. At the 2 higher monthly doses, the changes from baseline in BMD were not significantly different from those in the 5-mg/d group. Mean BTM values were decreased significantly from baseline in all 4 treatment groups, and the changes from baseline at 6 months at the 2 higher monthly doses were not significantly different from those at 5 mg/d.

CONCLUSIONS

Overall, in this study, the safety profiles of risedronate 100, 150, and 200 mg/mo were not different from that of risedronate 5 mg/d. Changes in efficacy measures in the monthly treatment groups were considered dose related and were not significantly different between the 5-mg/d group and the 150- and 200-mg/mo groups; similarity was greatest with 150 mg/mo.

Authors+Show Affiliations

Centre de Recherche du CHUM, Hôpital Saint-Luc, Montreal, Quebec, Canada. smalg@sympatico.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19302900

Citation

Ste-Marie, Louis-Georges, et al. "Comparison of the Effects of Once-monthly Versus Once-daily Risedronate in Postmenopausal Osteoporosis: a Phase II, 6-month, Multicenter, Randomized, Double-blind, Active-controlled, Dose-ranging Study." Clinical Therapeutics, vol. 31, no. 2, 2009, pp. 272-85.
Ste-Marie LG, Brown JP, Beary JF, et al. Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-controlled, dose-ranging study. Clin Ther. 2009;31(2):272-85.
Ste-Marie, L. G., Brown, J. P., Beary, J. F., Matzkin, E., Darbie, L. M., Burgio, D. E., & Racewicz, A. J. (2009). Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-controlled, dose-ranging study. Clinical Therapeutics, 31(2), 272-85. https://doi.org/10.1016/j.clinthera.2009.02.012
Ste-Marie LG, et al. Comparison of the Effects of Once-monthly Versus Once-daily Risedronate in Postmenopausal Osteoporosis: a Phase II, 6-month, Multicenter, Randomized, Double-blind, Active-controlled, Dose-ranging Study. Clin Ther. 2009;31(2):272-85. PubMed PMID: 19302900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-controlled, dose-ranging study. AU - Ste-Marie,Louis-Georges, AU - Brown,Jacques P, AU - Beary,John F, AU - Matzkin,Ellen, AU - Darbie,Lynn M, AU - Burgio,David E, AU - Racewicz,Artur J, PY - 2008/11/21/accepted PY - 2009/3/24/entrez PY - 2009/3/24/pubmed PY - 2009/5/13/medline SP - 272 EP - 85 JF - Clinical therapeutics JO - Clin Ther VL - 31 IS - 2 N2 - BACKGROUND: Risedronate 5 mg/d is approved by the US Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. Once-monthly dosing options might increase treatment compliance and persistence. OBJECTIVE: The aim of this study was to compare the tolerability and efficacy of 3 once-monthly risedronate dosing regimens with those of risedronate 5 mg/d. METHODS: This Phase II, 6-month, randomized, double-blind, active-controlled, dose-ranging study was conducted at 13 clinical research centers and hospitals in Croatia, Poland, Canada, and the United States between April 2004 and June 2005. Post-menopausal women aged 50 to 85 years with a lumbar spine T-score <-2.0 were randomly assigned to 1 of 4 treatment groups: risedronate 100, 150, or 200 mg/mo or 5 mg/d (active control), administered PO for 6 months. Evaluation of tolerability, the primary study objective, was based on adverse-event (AE) profiles and clinical laboratory values. Efficacy evaluation, a secondary objective, was a noninferiority comparison of the changes from baseline in bone mineral density (BMD) and bone turnover markers (BTMs). RESULTS: Of 370 patients randomized (91, 88, 88, and 103 patients in the risedronate 100-, 150-, and 200-mg/mo and 5-mg/d groups, respectively), 57% were > or =65 years of age and 99% were white; 316 patients (85.4%) completed the study. Completion rates were not significantly different across treatment groups, nor were reasons for discontinuation. Between-group differences in the incidences of treatment-emergent AEs, serious AEs, and upper gastrointestinal (GI) AEs were nonsignificant. Overall, 6 (7%), 14 (16%), 6 (7%), and 9 patients (9%) withdrew because of AEs in the 100-, 150-, and 200-mg/mo and 5 mg/d groups, respectively. GI disorders were the AEs that most frequently led to study withdrawal (5 [5.5%], 7 [8.0%], 4 [4.5%], and 6 [5.8%]). No trends were observed in the nature or frequency of other AEs causing withdrawal. All serious AEs were considered unrelated to treatment, with the exception of erosive esophagitis in 1 patient (1%) who received the 5-mg/d dose. Mean percentage increases in BMD were 2.10%, 2.99%, and 3.38% with risedronate 100, 150, and 200 mg/mo, respectively, versus 3.05% with 5 mg/d. At the 2 higher monthly doses, the changes from baseline in BMD were not significantly different from those in the 5-mg/d group. Mean BTM values were decreased significantly from baseline in all 4 treatment groups, and the changes from baseline at 6 months at the 2 higher monthly doses were not significantly different from those at 5 mg/d. CONCLUSIONS: Overall, in this study, the safety profiles of risedronate 100, 150, and 200 mg/mo were not different from that of risedronate 5 mg/d. Changes in efficacy measures in the monthly treatment groups were considered dose related and were not significantly different between the 5-mg/d group and the 150- and 200-mg/mo groups; similarity was greatest with 150 mg/mo. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/19302900/Comparison_of_the_effects_of_once_monthly_versus_once_daily_risedronate_in_postmenopausal_osteoporosis:_a_phase_II_6_month_multicenter_randomized_double_blind_active_controlled_dose_ranging_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(09)00055-1 DB - PRIME DP - Unbound Medicine ER -