Clinical Trial Result Information

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

Fast Facts:

Protocol number:	MA17843
Sponsor:	F. Hoffmann-La Roche Ltd
Company division:	Pharmaceutical
Product name:	Bonviva/Boniva
Generic name:	ibandronate
Phase of development:	IV
Therapeutic area, approved indication:	Post-Menopausal Osteoporosis
Date of report:	6/30/2005

Clinical study summary:
This 6-month (3 months and 12 weeks), 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) :
48 centers in the United States.

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

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

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):
342 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 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 – Significantly more patients preferred Bonviva 150-mg oral once-monthly tablets than alendronate 70-mg oral once-weekly tablets (71.4% vs 28.6%, P [Gart]=0.0000 in patients stating a preference (93%)), and the order of intake of the 2 medications did not have an impact on patient preference (P [Gart-order-effect]=0.1855). Significantly more patients also considered Bonviva once-monthly more convenient than alendronate once-weekly (74.6% vs 25.4%, P [Gart]<0.0000), and the order of intake of the 2 medications did not have an impact on patient opinion regarding convenience (P [Gart-order-effect]=0.1570).

Safety – No safety concerns were identified. The incidence of patients experiencing ≥1 AE was similar between treatments: Bonviva, 37.1%, alendronate, 35.9%. AEs with an incidence of ≥2% during Bonviva and alendronate treatment, respectively, were diarrhea (3.4 % vs 0.6%), nausea (3.7% vs 3.4%), and arthralgia (2.5% vs 1.6%). Other AEs occurred with lower incidences. Fifteen serious adverse events (SAEs) were reported: 11 occurred during Bonviva treatment and 4 during alendronate treatment. None of these incidences was reported as being related to study drug, and most of the incidences were due to a worsening or an exacerbation of a pre-existing disease, and were consistent with the population of elderly women enrolled in the study. A similar percentage of patients experienced ≥1 drug-related AE: Bonviva, 17.4%; alendronate, 17.8%. The percentage of patients withdrawn from study treatment because of an AE was slightly higher during alendronate (5.3%) treatment than during Bonviva (3.7%) treatment. Fourteen patients withdrew from treatment because of possibly or probably related AEs while receiving alendronate compared with 5 while receiving Bonviva. The majority of these were gastrointestinal AEs.

Conclusions:
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 (71.4% vs 28.6%, respectively) with post-menopausal osteoporosis who expressed a preference. In addition, most women (74.6% vs 25.4%, respectively) considered once-monthly Bonviva treatment to be more convenient than alendronate once-weekly. Overall, no safety concerns were identified, and both treatments were similarly well tolerated.

Click here for the protocol registry listing of this trial.