Clinical Trial Result Information

Protocol number
MA17844

Title of Study
Randomized, Open-Label, Multi-Center Study to Investigate Patient Preference on Dosing in Women With Postmenopausal Osteoporosis Treated With Once-Monthly Ibandronate and Once-Weekly Alendronate. A 6-Month, 2-Sequence, and 2-Period Crossover Study

Sponsor
F Hoffmann-La Roche Ltd

Company division
Pharmaceutical

Product name
Bonviva/Boniva

Generic name
ibandronate

Therapeutic area
Post-Menopausal Osteoporosis

Clinical study summary
This 6-month, prospective, randomized, open-label, 2-sequence, 2-period crossover study evaluated patient preference for Bonviva (ibandronate) or alendronate. Patients received Bonviva (Sequence A) or alendronate (Sequence B) for 3 months followed by 3 months of the alternate therapy. Study visits were scheduled at Months 3 and 6. Patients who had taken ≥1 dose of each study drug were asked to complete a Preference Questionnaire (at the 6-month study visit or at the early-termination visit).

Study center(s)
52 centers in France, Germany and US.

Phase of development
IV

Objectives
Primary objective: To evaluate patient reported preference for either the once-monthly Bonviva regimen or the once-weekly alendronate regimen.

Secondary objective: To investigate the convenience of the once-monthly Bonviva regimen vs the once-weekly alendronate regimen.

Safety: (1) Adverse events (AEs); and (2) Safety laboratory tests.

Methodology
Clinical assessments were performed at screening and baseline visits (medical history, physical examination, laboratory assessments) and at the final visit (laboratory assessments). Patients were scheduled for study visits at Months 3 (crossover) and 6 (final). Patients who had taken ≥1 dose of each study medication were asked to complete a Preference Questionnaire (at the 6-month or early-termination visit).

Number of patients (planned/analyzed)
350 randomized.

Diagnosis and main criteria for inclusion
Ambulatory women with post-menopausal osteoporosis, as determined by the treating physician, who had never received bisphosphonate therapy (bisphosphonate-naïve) or patients who discontinued daily bisphosphonate ≥3 months prior to study entry for reasons other than treatment emergent AEs (lapsed daily bisphosphonate users).

Test product, dose and mode of administration or test procedure
Bonviva (ibandronate) 150 mg/month/po.

Duration of treatment
3 months.

Reference therapy, dose and mode of administration or reference procedure
Alendronate 70 mg/week/po.

Criteria for evaluation (efficacy, safety)
Efficacy parameters: Proportion (%) of patients preferring once-monthly dosing with Bonviva over once-weekly dosing with alendronate.

Safety parameters: (1) AEs; and (2) Laboratory tests.

Statistical methods
The primary parameter of preference for the monthly Bonviva over the weekly alendronate regimen was tested using Gart’s test. Subjects with no preference were excluded from this test because it includes only data with a preference of one treatment over the other. The primary parameter of preference for the monthly Bonviva over the weekly alendronate regimen was also tested using the Prescott test, which includes all data (preference and no- preference). The effect of the sequence of treatments was also tested using Gart’s test. All tests were 2-sided with a significance level of .05.

The secondary endpoint of convenience was also tested using Gart’s and Prescott’s tests. This parameter and the primary parameter were summarized by descriptive statistics, including 95% confidence intervals (CIs).

Summary (efficacy, safety, other results)
Efficacy: The primary study objective was met. Among the patients who expressed a preference for either treatment, a greater number of patients preferred the once-monthly Bonviva regimen (70.6%) over the once-weekly alendronate regimen (29.4%). The preference of the once-monthly Bonviva regimen was statistically significant (P<0.0001); a total of 93% of patients expressed a preference. Also, the once-monthly Bonviva schedule (76.6%) was observed to be more convenient than the once-weekly alendronate schedule (23.4%) and this difference was statistically significant (P<0.0001).
Of those patients that expressed a preference for either once-monthly Bonviva or once-weekly alendronate, most considered that their preferred regimen was easier to follow in the long-term, and that the dosing schedule better fitted their lifestyle.

Safety: Overall, both treatments showed a similar safety profile. Only diarrhea, constipation, nausea, upper abdominal pain, arthralgia, back pain and headache occurred in 2% or more patients during any treatment period. Gastrointestinal disorders leading to withdrawal from trial treatment as well as those rated as severe in intensity were reported more often in patients while on alendronate treatment than while on Bonviva treatment. The incidence of serious adverse events was similar during the periods of Bonviva or alendronate and consistent with the population of elderly women enrolled in the study.

Conclusions
The results of this study show that oral dosing with once-monthly 150 mg Bonviva was preferred over once-weekly 70 mg alendronate by the majority of women with postmenopausal osteoporosis (70.6% vs 29.4%, respectively) who expressed a preference. In addition, more patients considered once-monthly Bonviva treatment to be more convenient than alendronate once-weekly (76.6% vs 23.4%, respectively). Overall, no safety concerns were identified, and both treatments were similarly well tolerated.

Publications (references, if available)
Hadji P et al. Women with postmenopausal osteoporosis prefer once-monthly oral ibandronate to weekly alendronate: results of BALTO II. Osteoporos Int 2006; 17 (Suppl.1): S69 (Abstract P259)

Date of report
1/1/2006

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