Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the monthly oral pilot study.

Abstract

Ibandronate, a potent, nitrogen-containing bisphosphonate developed for intermittent administration in postmenopausal osteoporosis, aims to overcome current adherence issues with daily and weekly oral bisphosphonates through once-monthly oral dosing. The purpose of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate. A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted. The study was conducted at five clinical trial centers in the United Kingdom and Belgium. Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post menopause; n = 144). Once-monthly oral ibandronate 50, 100, or 150 mg or placebo was used. After the first cycle, the 50-mg arm was split, with participants continuing on either 50 or 100 mg. Primary outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum ibandronate AUC0-infinity. Once-monthly oral ibandronate was well tolerated, with a similar overall and upper gastrointestinal safety profile to placebo. Once-monthly ibandronate was also highly effective in decreasing bone turnover; substantial reductions from baseline in serum CTX (-56.7% and -40.7% in the 150- and 100-mg arms, respectively; P < 0.001 vs. placebo) and urinary CTX (-54.1% and -34.6%, respectively; P < 0.001 vs. placebo) were observed at d 91 (30 d after the final dose). Analysis of the area under the effect curve (d 1-91) for change from baseline (percent x days) in serum CTX and urinary CTX indicated a dose-response relationship. The AUC0-infinity for ibandronate increased with dose but not in a dose-proportional manner. These findings indicate a potential role for once-monthly oral ibandronate in the treatment of postmenopausal osteoporosis.