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

CONTEXT 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. OBJECTIVE The purpose of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate. DESIGN A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted. SETTING The study was conducted at five clinical trial centers in the United Kingdom and Belgium. PATIENTS OR OTHER PARTICIPANTS Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post menopause; n = 144). INTERVENTION(S) 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. MAIN OUTCOME MEASURE(S) Primary outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum ibandronate AUC0-infinity. RESULTS 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. CONCLUSIONS These findings indicate a potential role for once-monthly oral ibandronate in the treatment of postmenopausal osteoporosis.