Roche trials database

Protocol number:

ML20088

Title of Study:

A randomized, double-blind study to evaluate the effect of once monthly Bonviva on lumbar bone mineral density in the prevention of glucocorticoid-induced osteoporosis in post-menopausal women

Sponsor:

Hoffmann-La Roche

Company division:

Pharmaceutical

Product name:

ibandronate [Bonviva/Boniva]

Generic name:

ibandronate

Therapeutic area:

• Post-Menopausal Osteoporosis

Clinical study summary:

This randomized, double-blind, parallel-group, placebo-controlled study was designed to evaluate the efficacy and safety of once monthly Bonviva/Boniva (ibandronate) in the prevention of glucocorticoid-induced osteoporosis in post-menopausal women. Patients were randomized to one of two treatment arms: Arm A: Bonviva/Boniva plus calcium and vitamin D, Arm B: Placebo plus calcium and vitamin D.

Study center(s):

13 centers in Finland

Phase of development:

IV

Objectives:

The primary objective was to compare the change from baseline in mean lumbar spine (L1-L4) bone mineral density (BMD) at 12 months between Bonviva/Boniva and placebo.

The secondary objectives were as follows: Change in mean lumbar spine (L1-L4) BMD at 6 months; change from baseline in total hip BMD at 6 and 12 months; change from baseline in bone turn over markers at 1, 6 and 12 months; difference in withdrawal rate due to worsening in BMD (BMD T-score at any site ≤ - 2.5 SD) at 6 months and or worsening in BMD at least 7% at any site at 6 months; incidence of adverse events.

Methodology:

A randomized, double-blind, placebo-controlled, parallel-group study of 140 post-menopausal women was conducted. At baseline the mean lumbar spine (LS) (L1–L4) bone mineral density (BMD) was normal or osteopenic (T-score ≥–2.0) and patients were receiving treatment with 5-15mg/day of prednisone equivalent.

Patients were randomized 1:1 to receive either monthly oral Bonviva/Boniva 150mg or placebo for 12 months. In addition, all patients received vitamin D and calcium supplements. Primary endpoint was the relative change from baseline at 12 months in mean lumbar spine BMD.

Number of patients (planned/analyzed):

140 patient enrolled and treated

Diagnosis and main criteria for inclusion:

Post-menopausal women, 50-85 years of age with any inflammatory rheumatoid disease including polymyalgia rheumatica and receiving treatment with 5-15 mg/day of prednisone equivalent.

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

ibandronate 150 mg orally once monthly

Calcium 1000 mg per day and vitamin D 800 IU per day

Duration of treatment:

12 months

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

Placebo to ibandronate orally once monthly

Criteria for evaluation (efficacy, safety):

Efficacy

Primary: Change from baseline in mean lumbar spine BMD at 12 months.

Secondary: Change from baseline in mean lumbar spine (L1-L4) BMD at 6 months; change from baseline in total hip BMD at 6 and 12 months; change from baseline in bone turnover markers at 1, 6 and 12 months; difference in withdrawal rate due to worsening in BMD (BMD T-score at any site ≤ - 2.5 SD) at 6 months and or worsening in BMD at least 7% at any site at 6 month.

Safety

Adverse events (clinical vertebral and non-vertebral fractures were reported as AEs); laboratory test results, vital signs; premature discontinuation of treatment for safety reasons.

Statistical methods:

The primary objective was to test the null hypothesis that the between-treatment difference in the mean relative change (%) from baseline in lumbar spine BMD at 12 month was not statistically significant. The primary endpoint was analyzed using analysis of covariance (ANCOVA). The primary model included treatment, center, duration of glucocorticoid treatment, diagnosis of rheumatic disease and baseline BMD as covariates. Treatment difference was assessed using least square means with a 95% confidence interval (CI).

Summary (efficacy, safety, other results):

At 6 and 12 months, a significant mean change from baseline was observed in mean LS BMD with Bonviva/Boniva (2.6% and 3.2%) compared with placebo (0.3% and -0.1%), respectively (p<0.001). For trochanter, femoral neck and total hip BMD, a significant mean change from baseline was observed at 12 months with Bonviva/Boniva compared with placebo, p<0.001. In the Bonviva/Boniva group the relative reduction in bone turnover markers was statistically greater than in placebo group at 1, 6 and 12 months.

Adverse events (AEs) were reported at a similar frequency in both groups (71.4% of patients in the Bonviva/Boniva group vs. 74.3% of patients in the placebo group). Serious AEs (SAEs) were reported in a higher proportion of patients in the Bonviva/Boniva group than in the placebo group (13 SAEs in 10 patients vs. 6 SAEs in 6 patients). No single SAE was more pronounced in the Bonviva/Boniva group.

Conclusions:

Once monthly oral Bonviva/Boniva provides a significant increase in lumbar spine and total hip bone mineral density with acceptable safety profile in postmenopausal women treated with glucocorticoids for inflammatory rheumatic diseases.

Date of report:

08.02.2011

Click here for the protocol registry listing of this trial.