Clinical Trial Result Information

Protocol number
MF 4376

Title of Study
Open, monocenter, pilot-study on the efficacy and safety of intermittent, intravenous administration of BM 21.0955 (2.0 mg every three months) during 2 years’ treatment in male patients with osteoporosis.

Sponsor
Roche Global Development

Company division
Pharmaceutical

Product name
Bonviva/Boniva

Generic name
ibandronate

Therapeutic area
Osteoporosis

Clinical study summary
This was an open-label, uncontrolled pilot study to evaluate the effect of intermittent intravenous administration of Bonviva in male patients with osteoporosis. All patients received iv bolus injections of 2mg Bonviva every 3 months for a total of 2 years. 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 MF 4380, 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 was not met. Thus, in this trial only primary efficacy was analyzed.

Study center(s)
2 sites in Switzerland and Czech Republic.

Phase of development
II

Objectives
To evaluate the anti-resorptive efficacy and the safety of Bonviva in the long-term treatment (intermittent intravenous bolus injections every three months for the duration of two years) of male patients with osteoporosis, as evaluated by the change in lumbar spine bone mineral density and biochemical bone markers.

Methodology
The two centers each recruited different types of patients: male patients with osteoporosis in one center and Klinefelter’s syndrome patients experiencing bone loss in the other. A 24 month treatment period was followed by a one year treatment free observation period. In addition to the study drug, all patients were to receive 1000 mg calcium per day as oral concomitant therapy.

Number of patients (planned/analyzed)
30

Diagnosis and main criteria for inclusion
Male patients with osteoporosis or Klinefelter’s syndrome.

Test product, dose and mode of administration or test procedure
Bonviva (ibandronate); intravenous bolus injection of 2.0 mg every 3 months

Duration of treatment
2 years.

Reference therapy, dose and mode of administration or reference procedure
None

Criteria for evaluation (efficacy, safety)
Efficacy: Primary: The relative change in bone mineral density (BMD) of the lumbar spine (L₁-L₄) at study end compared to baseline.
Secondary: The relative change in BMD of the lumbar spine (L₁-L₄), the distal forearm and the proximal femur.
Safety: Adverse events (AE); laboratory parameters of renal function, hepatic function, hematology and electrolytes.

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

Summary (efficacy, safety, other results)
Efficacy: In male patients with osteoporosis the total lumbar spine BMD showed a mean increase of 4.16% relative to baseline over the first 12 months of the study and of 6.25% over the first 24 months of the study. In patients with Klinefelter’s syndrome the total lumbar spine BMD showed a mean increase of 9.08% relative to baseline over the first 12 months of the study and of 11.33% over the first 24 months of the study.

Safety: The intravenous administration of 2.0 mg Bonviva was well tolerated. The adverse events most commonly reported were flu syndrome (8 patients, 26.7%), leukocytosis (5 patients, 16.7%), back pain, monocytosis, bronchitis, and osteoporotic fracture (3 patients each, 10%). The frequency and type of AEs was similar in both populations of patients.
Four patients withdrew prematurely from the study due to adverse events, coded as depression, flu syndrome, stomach ulcer, and joint disorder. A total of 8 patients experienced a serious adverse event during the study. Only one of these, flu syndrome, was considered to be related to the study drug.
Analysis of the laboratory safety data for both hematology and blood biochemistry did not identify any trends raising clinical concern. Decreases in serum magnesium, phosphate, and potassium concentrations led to marked laboratory abnormalities in 8, 7, 6 patients respectively.

Conclusions
The results of this study indicate that 2.0 mg Bonviva administered as an iv injection every 3 months for 2 years, increased lumbar spine BMD and was well tolerated in male patients with osteoporosis and in patients with Klinefelter’s syndrome suffering from osteoporosis.

Date of report
9/1/2001