Clinical Trial Result Information
Protocol number
BP16331
Title of Study
Randomized, double-blind, placebo-controlled, multicentre, dose-ranging study to determine the tolerability and effect on bone turnover of several monthly doses of ibandronate in postmenopausal osteopenic and osteoporotic women.
Sponsor
F Hoffmann-La Roche Limited
Company division
Pharmaceutical
Product name
Bonviva/Boniva
Generic name
ibandronate
Therapeutic area
Post-Menopausal Osteoporosis
Clinical study summary
This was an open label, placebo-controlled study to investigate the efficacy and safety of several monthly dosage regimens of Bonviva in post-menopausal women with osteoporosis or osteopenia. Bonviva, or placebo, was administered monthly for 3 months.
Study center(s)
A total of 5 sites in Belgium and UK.
Phase of development
II
Objectives
To determine the tolerability, bioavailability and effect on bone turnover of different monthly doses of ibandronate in postmenopausal osteopenic or osteoporotic women.
Methodology
After screening, 144 postmenopausal women were included in study. Monthly doses of Bonviva were administered in doses of 50, 50 escalating to 100 in months 2 and 3, 100, 150 mg p.o. or placebo. PD, PK & safety data were collected up to 31 days after 1st and 3rd treatments. Safety data were collected throughout the study.
Number of patients (planned/analyzed)
A total of 144 patients were randomized.
Diagnosis and main criteria for inclusion
Postmenopausal women; at least 3 years since natural menopause; aged 55-80 years; daily intake of at least 500 mg Ca2+ from food sources as per FFQ.
Test product, dose and mode of administration or test procedure
Bonviva (ibandronate) film coated tablets.
50 mg, p.o. on Day 1, Day 31 and Day 61
50 mg p.o. on Day 1, then 100 mg on Day 31 and Day 61
100 mg, p.o. on Day 1, Day 31 and Day 61
150 mg, p.o. on Day 1, Day 31 and Day 61
Duration of treatment
3 monthly treatments
Reference therapy, dose and mode of administration or reference procedure
Placebo film coated tablets p.o. on Day 1, Day 31 and Day 61.
Criteria for evaluation (efficacy, safety)
Pharmacodynamics: Relative change from baseline (%) at Day 91 for each bone resorption marker (serum C-telopeptide (CTX), urine C-telopeptide (U-CTX) and urine N-telopeptide (U-NTX)).
Pharmacokinetics: Primary: The area under the concentration time curve AUC0-∞ after the first dose of each dose group.
Safety: Adverse events and laboratory tests.
Statistical methods
Pharmacodynamic parameters: Relative change from baseline in bone resorption markers tested for significance using Kruskal-Wallis Test, pairwise comparison of active vs placebo groups using Extended Wilcoxon Rank Sum tests.
Pharmacokinetic parameters: One-way ANOVA applied to the dose normalized AUC with dose as factor.
Safety data: Frequency and incidence of all adverse events. Descriptive statistics for changes and trends in laboratory variables.
Summary (efficacy, safety, other results)
Pharmacodynamics: Bonviva decreased bone resorption markers CTX in serum and urine, and NTX in urine. The decreases of CTX relative to placebo were statistically significant in the dose range 100 to 150 mg, with 150 mg leading to decreases in serum CTX of 57% and urine CTX of 54% on Day 91.
Pharmacokinetics: Dose-normalized AUCs relative to the 50 mg dose were 130% (100 mg) and 191% (150 mg), relative Cmax values were 124% (100 mg) and 167% (150 mg). The relationships between AUC and Cmax and dose were not directly proportional.
Safety: The distribution of adverse events in the five treatment groups, their intensity, temporal relationship to drug intake and relatedness suggest that multiple doses of Bonviva up to 150 mg were well tolerated and did not lead to an increased number of adverse events compared with placebo. No serious adverse events or deaths were reported throughout the study. Adverse events led to the withdrawal of only three subjects from the study.
Conclusions
Bonviva treatment led to marked inhibition of bone resorption in postmenopausal women. The increases in Cmax and AUC were greater than dose-proportional. Bonviva was well tolerated in monthly doses up to 150 mg.
Publications (references, if available)
Reginster J-Y et al. Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the Monthly Oral Pilot Study. J Clin Endocrinol Metab 2005; 90:5018-24.
Date of report
10/20/2006
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