Clinical Trial Result Information

Protocol number
MF 4380F

Title of Study
Double-blind, placebo-controlled, randomized, multicenter study on the efficacy and safety of ibandronate (BM 21.0955) during an extended two year parallel group study of patients enrolled in MF 4380 (3-year post-menopausal osteoporosis treatment study) using an intermittent i.v. injection regimen of 0.5 mg and 1 mg every 3 months.

Sponsor
Roche Global Development

Company division
Pharmaceutical

Product name
Bonviva/Boniva

Generic name
ibandronate

Therapeutic area
Postmenopausal Osteoporosis

Clinical study summary
This was a randomized, placebo-controlled, double-blind parallel group study in patients with post-menopausal osteoporosis, who were previously enrolled in study MF 4380. They were to receive intermittent (every 3 months) iv injections of placebo, 0.5 mg or 1.0 mg Bonviva for two years. In addition to study medication, all patients received supplemental doses of calcium (500 mg/day) and vitamin D (400 IU/day). The study was discontinued prematurely by the sponsor following the outcome of the phase 3 fracture trial, MF 4380, in women with postmenopausal osteoporosis. In this study, the magnitude of fracture reduction with doses of 0.5 mg and 1.0 mg administered every 3 months was suboptimal and thus the primary endpoint of the study (a statistically significant reduction in vertebral fractures over 3 years in the full intent-to-treat population) was not met.

Study center(s)
42 centers in Belgium, Canada, Czech Republic, Denmark, France, Germany, Norway, Netherlands, Norway, Poland and UK

Phase of development
III

Objectives
The objective of study MF 4380F was to extend from 3 to 5 years the safety and efficacy experience of post-menopausal osteoporotic women treated once every 3 months with iv Bonviva.

Methodology
All safety data for study MF 4380F were collected through to the final assessment for all patients who received at least one dose of study medication. Measurements for the primary efficacy endpoint [bone mineral density (BMD) of lumbar spine] were performed at the patient’s final visit. All other efficacy assessments were discontinued without a formal final assessment.

Number of patients (planned/analyzed)
A total of 1192 patients were randomized into the trial.

Diagnosis and main criteria for inclusion
Postmenopausal females, having completed MF 4380 according to the protocol.

Test product, dose and mode of administration or test procedure
Bonviva (ibandronate); intravenous bolus injection of 0.5 mg or 1.0 mg every 3 months

Duration of treatment
2 years.

Reference therapy, dose and mode of administration or reference procedure
Placebo iv every 3 months

Criteria for evaluation (efficacy, safety)
Efficacy: Primary: The mean relative change in bone mineral density (BMD) of the lumbar spine (L1-L4) at study end compared to baseline.
The secondary variables assessed for efficacy were the change in BMD at the proximal femur and distal forearm, height, pain and disability, pharmacoeconomics, and change in biochemical markers of bone turnover.

Safety: Adverse events (AE); laboratory parameters of renal function, hepatic function, hematology and electrolytes.

Statistical methods
Only a very abbreviated analysis of the efficacy data was performed.

Summary (efficacy, safety, other results)
Efficacy: Since the study was prematurely discontinued, only 52% of the patients completed 1 year of the treatment, therefore valid conclusions could not be drawn with respect to efficacy.

Safety: The intravenous administration of Bonviva was well tolerated. The most commonly reported AEs were accidental injury, upper respiratory infection, back pain, arthralgia, and pain in extremity.
A total of 13 patients withdrew prematurely from the study due to adverse events, and a total of 90 patients (7.6%) experienced a serious adverse event during the study. Only one of these, a cerebral infarct, was considered to be related to the study drug.
Analysis of the laboratory safety data for both haematology and blood biochemistry did not identify any trends raising clinical concern.

Conclusions
Results from study MF 4380F showed that patients who continued receiving intermittent iv injections of Bonviva every 3 months had a similar profile to patients on placebo. No safety concerns were identified in the Bonviva-treated groups, and treatment was well tolerated.

Date of report
5/1/2002