Roche trials database

Protocol number:

MA19547

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 risedronate. A six-month, two-sequence, and two-period crossover study.

Sponsor:

Hoffmann-La Roche

Company division:

Pharmaceutical

Product name:

Bonviva/Boniva

Generic name:

ibandronate

Therapeutic area:

• Post-Menopausal Osteoporosis

Clinical study summary:

This was a 6 month prospective, randomized, open-label, multi-center, 2-period and 2-sequence crossover study. After screening, eligible patients were randomized into either Sequence A or B. Patients randomized to Sequence A started with oral Bonviva ( ibandronate) once-monthly 150 mg for 3 calendar months, followed by oral risedronate once-weekly 35 mg for 12 weeks. Patients randomized to Sequence B started with risedronate weekly for 12 weeks followed by Bonviva once-monthly for 3 calendar months. The crossover (Visit 3) took place once the patient had completed 3 calendar months of treatment with Bonviva (Sequence A) or 12 weeks treatment with risedronate (Sequence B). There was no wash-out period between the two treatment regimens. The study duration was approximately 6 months (3 months and 12 weeks). A follow-up period of 15 days after the completion of treatment was included to assure collection of additional information on safety.

Study center(s):

44 centers in United States

Phase of development:

IV

Objectives:

The primary objective was to evaluate patient reported preference for either the once-monthly dosing regimen of Bonviva or the once-weekly dosing regimen of risedronate.
Secondary objectives were to investigate the convenience of the once-monthly dosing regimen of Bonviva versus the once-weekly dosing regimen of risedronate; to evaluate the relative and absolute changes from baseline in serum CTX (bone resorption marker) and serum BSAP (bone formation marker) at the end of the first treatment periods (before the cross-over to the alternative treatment regimen); and to evaluate patient-reported upper gastrointestinal tolerability of weekly risedronate and monthly Bonviva during first 12 weeks of the study.

Methodology:

Patients were scheduled for study visits at Months 3 (crossover) and 6 (final). A Follow-up telephone call was performed 15 days after the final visit. Patients who had taken at least one dose of each study medication were asked to answer a Preference Questionnaire (answered by patients before any study procedures took place at the 6 month visit or at the early termination visit). No assistance was allowed in completing the questionnaire. Patients were asked to complete a weekly questionnaire on upper GI tolerability for the first 12 weeks of the study.

Number of patients (planned/analyzed):

356 enrolled and treated

Diagnosis and main criteria for inclusion:

Ambulatory women with postmenopausal osteoporosis, age 55-80 years, who had never received bisphosphonate therapy (bisphosphonate naïve) or previously received oral daily or i.v bisphosphonate, and who, in the opinion of the investigator, are able to understand and complete the Preference Questionnaire, and willing and able to comply with the protocol requirements.

Test product, dose and mode of administration or test procedure:

Once-monthly, single tablet of Bonviva (ibandronate) 150 mg orally administered for 3 months.

Duration of treatment:

3 months

Reference therapy, dose and mode of administration or reference procedure:

Once weekly, commercially available single tablet of risedronate 35 mg orally administered for 12 weeks.

Criteria for evaluation (efficacy, safety):

The primary efficacy parameter was the proportion (%) of patients preferring once-monthly dosing with Bonviva over once-weekly dosing with risedronate. Secondary efficacy parameters were the proportion (%) of patients who found once-monthly dosing with Bonviva more convenient than once-weekly dosing with risedronate and the change in bone turnover markers. Safety parameters were adverse events, upper gastrointestinal tolerability and laboratory test parameter abnormalities.

Statistical methods:

The primary parameter of preference for the monthly Bonviva regimen over the weekly risedronate regimen was tested using Gart’s test which excludes patients with no preference of one treatment over the other. Prescott’s test was also used which includes all data (preference and no preference data). The effect of sequence of treatments (i.e. to test whether the proportion of patients who preferred the monthly regimen was same for each sequence) was also tested using Gart's test. All the tests were two-sided with a significance level of 0.05.
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.

Summary (efficacy, safety, other results):

Efficacy: The primary study objective was met. Among the patients who expressed a preference for either treatment, a significantly greater number of patients preferred once-monthly Bonviva (79.9%) over once-weekly risedronate (21.1%) (P<0.0001). Patients also reported that once-monthly dosing with Bonviva was significantly more convenient than once-weekly risedronate (86.3% vs 13.7%, respectively ) (P<0.0001).
Patient preference for and the convenience of once-monthly Bonviva over once-weekly risedronate did not appear to depend on the order of intake of the two drugs and was independent of the age or the working status of the patients. Of those patients who expressed a preference for either once-monthly Bonviva or once-weekly risedronate, most considered that their preferred regimen was easier to follow for a long time, and that the dosing schedule better fitted their lifestyle.

Safety: Overall, both treatments showed a similar safety profile. The frequency and intensity of upper GI symptoms, which were recorded during the first 12 weeks of treatment by the patients in a weekly diary using a pre-defined list, were similar between the two treatments.
Only nausea, dyspepsia, abdominal distension, stomach discomfort, gastroesophageal reflux disease abdominal pain upper, and bronchitis occurred in 2% or more patients during any treatment period, and the incidence of these events was similar with both Bonviva monthly and risedronate weekly dosing.
Gastrointestinal disorders leading to withdrawal from trial treatment as well as those rated by the investigators as severe in intensity occurred slightly more frequently in patients while on Bonviva treatment, than while on risedronate treatment.
The incidence of serious adverse events was similar during the periods of Bonviva or risedronate treatment 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 35 mg risedronate by the majority of women with postmenopausal osteoporosis who expressed a preference (79.9% vs. 21.1%, respectively; P<0.0001). In addition, more patients considered once-monthly Bonviva treatment to be more convenient than risedronate once-weekly (86.3% vs. 13.7%, respectively; P<0.0001). Overall, no safety concerns were identified, and both treatments were similarly well tolerated.
These results are consistent with those seen in two previous studies of identical design comparing preference and convenience of monthly Bonviva versus weekly alendronate, and suggest that once-monthly dosing with an oral bisphosphonate has the potential to improve adherence.

Publications (references, if available):

None

Date of report:

01.09.2008

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