Clinical Trial Result Information

Title of Study:
Open-label, single-arm, multicenter, follow-up study on the efficacy and safety of intermittent, intravenous administration of BM 21.0955 (1.0 mg every 3 months) during 3 years’ treatment of patients with post-menopausal osteoporosis.

Fast Facts:

Protocol number:	MF 4407
Sponsor:	Roche Global Development
Company division:	Pharmaceutical
Product name:	Bonviva/Boniva
Generic name:	ibandronate
Phase of development:	II
Therapeutic area, approved indication:	Postmenopausal Osteoporosis
Date of report:	8/1/2000

Clinical study summary:
This was a follow-up open-label, single-arm, multicenter study in patients with postmenopausal osteoporosis, who were previously enrolled in MF 4361.

Study center(s) :
3 centers in Netherlands and Switzerland.

Objectives:
To evaluate the safety and anti-resorptive efficacy of intermittent, intravenous administration of Bonviva over 3 years in postmenopausal osteoporotic patients as evaluated by the change in lumbar spine bone mineral density and biochemical bone markers.

Methodology:
Consenting patients who had participated in MF 4361 were invited to enter the present follow-up study (MF 4407). The study used the baseline from MF 4361 and all patients were assigned to treatment with 1.0 mg intravenous Bonviva every 3 months for 3 years. Patients received calcium concomitantly. BMD measurements as well as laboratory efficacy and safety assessments were performed at regularly scheduled visits. Adverse events were collected continuously throughout the trial.

Number of patients (planned/analyzed):
Planned: 40 patients. Enrolled: 45 patients.

Diagnosis and main criteria for inclusion:

Diagnosis: Postmenopausal osteoporosis.
Inclusion criteria: Female patients who completed study MF 4361 and agreed to participate in the follow-up trial.

Test product, dose and mode of administration or test procedure:
Bonviva (ibandronate). Intravenous bolus injection of 1.0 mg Bonviva every 3 months

Duration of treatment:
3 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 (L₂-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; the change in urinary markers of bone turnover.
Safety: Adverse events (AE); laboratory parameters of renal function, hepatic function, hematology and electrolytes.

Statistical methods:
Data were summarized using descriptive statistics with changes assessed relative to the baseline of the preceding study MF 4361. Only an abbreviated analysis of the efficacy data was performed.

Summary (efficacy, safety, other results):
Efficacy: The total lumbar spine BMD (L₂-L₄) showed a mean increase of 5.2% relative to baseline (MF 4361) and a mean increase of 4.1% over the 3-year period of the study with the change in BMD varying substantially between individual patients.

Safety: The intravenous administration of 1.0 mg Bonviva was well tolerated over the 3-year period of the study. A total of 7 patients (16%) experienced an AE assessed as possibly or probably related to the study treatment. There were no SAEs or patient withdrawals assessed as related to treatment and no deaths occurred during the study. The most commonly experienced adverse events were upper respiratory infection (29%), back pain (18%), bronchitis (16%) and arthralgia (13%).
While serum alkaline phosphatase decreased relative to baseline (MF 4361), this observation was consistent with the expected effects of bisphosphonates on the inhibition of bone turnover. Analysis of the laboratory safety parameters did not identify any trends raising clinical concern.

Conclusions:
The results of this study suggest that intermittent administration of 1.0 mg Bonviva increased lumbar spine BMD [L₂-L₄] and was well tolerated by patients being treated for postmenopausal osteoporosis when administered intravenously at 3-month intervals over a period of 3 years.