Clinical Trial Result Information

Title of Study:
A two-center, randomized, comparative study using 2 mg intermittent iv ibandronate and 10 mg daily oral alendronate during 2 years in the treatment of post-menopausal osteoporosis.

Fast Facts:

Protocol number:	MF 4472
Sponsor:	Roche Global Development
Company division:	Pharmaceutical
Product name:	Bonviva/Boniva
Generic name:	ibandronate
Phase of development:	III
Therapeutic area, approved indication:	Postmenopausal Osteoporosis
Date of report:	7/1/2001

Clinical study summary:
This study was planned as an open-label, two-center, active-controlled, randomized, parallel-group investigation. Patients were randomized to receive either intermittent Bonviva 2mg iv or daily alendronate 10mg po for 2 years. The study was discontinued prematurely by the Sponsor following the outcome of the Phase 3 fracture trial, MF4380, in women with postmenopausal osteoporosis. In MF4380, the magnitude of fracture reduction with doses of 0.5mg and 1.0mg administered every 3-months was suboptimal and thus the primary endpoint of the study was not met. Thus, in this trial patient data were assessed for the first study year only.

Study center(s) :
2 centers in Poland

Objectives:
To evaluate the effects of Bonviva administration on bone quality and bone turnover by histomorphometry, using paired biopsies prior to and following 22 months of treatment, and to compare the efficacy of 2.0 mg intermittent iv Bonviva with 10 mg oral daily alendronate in the treatment of postmenopausal osteoporosis.

Methodology:
BMD measurements were to be performed prior to drug administration, and at 12 month intervals thereafter. Laboratory efficacy and safety assessments were performed according to a predefined schedule, using standard technology. Adverse events were collected continuously throughout the trial.

Number of patients (planned/analyzed):
Planned: 60 patients. Randomized: 66 patients.

Diagnosis and main criteria for inclusion:
Women with postmenopausal osteoporosis, with a lumbar spine BMD [L₁-L₄] < -2.5 SD T-score, at least 5 years since menopause, aged between 55-75 years at the time of randomization.

Test product, dose and mode of administration or test procedure:
2.0 mg Bonviva (ibandronate)/iv./every 3 months

Duration of treatment:
2 years planned

Reference therapy, dose and mode of administration or reference procedure:
10 mg alendronate (Fosamax®)/oral/o.d.

Criteria for evaluation (efficacy, safety):
Efficacy: Primary: Osteoid thickness in cancellous bone was planned to be assessed after 2 years but paired biopsies were not performed due to the premature termination of the study.
Secondary: The relative change from baseline in lumbar spine BMD [L₁–L₄] and proximal femur (total hip, femoral neck, trochanter, and Ward’s triangle), the relative change in biochemical markers of bone turnover, and the relative change in mineralizing surface.
Safety: Adverse events (AE); laboratory parameters of renal function, hepatic function, hematology and electrolytic balance.

Statistical methods:
A descriptive analysis was performed for changes in BMD, bone turnover and mineralizing surface.

Summary (efficacy, safety, other results):
Efficacy: As a result of the premature termination of the study, no follow-up data was available for the primary variable and this variable was not assessed. Patients in the Bonviva and alendronate treatment arms showed median last value changes in lumbar spine [L₁-L₄] BMD of 4.3% and 4.5% respectively.

Safety: The iv administration of 2.0 mg Bonviva was well tolerated. Upper respiratory infection was the most commonly reported AE in the Bonviva treatment group (3 patients, 9%). One SAE was reported in the Bonviva treatment group (urinary incontinence). No AEs or SAEs were considered to be related to study treatment and no deaths were reported during the study.
Analysis of the laboratory safety data for renal function, hepatic function, electrolytic balance and haematology did not identify any trends raising clinical concern.

Conclusions:
The results from this study suggest that treatment with 2.0 mg iv Bonviva quarterly was well tolerated in patients with post-menopausal osteoporosis.