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


METHODS
A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted.


METHODS
The study was conducted at five clinical trial centers in the United Kingdom and Belgium.


METHODS
Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post menopause; n = 144).


METHODS
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.


METHODS
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.
Reginster
Jean-Yves
JY
Unité d'Exploration du Metabolisme de l'Os et du Cartilage, Centre Hospitalier Universitaire Centre Ville, B-4020 Liège, Belgium. jyreginster@ulg.ac.be
Wilson
Katie M
KM
Dumont
Etienne
E
Bonvoisin
Bernard
B
Barrett
Joanne
J
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control; D003094:Collagen / Q000097:blood / Q000652:urine; D024042:Collagen Type I; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D000077557:Ibandronic Acid; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D010455:Peptides / Q000097:blood / Q000652:urine
D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000077557:Ibandronic Acid