Clinical Trial Result Information

Title of Study:
Open-label, single-arm, multicenter study on the efficacy and safety of intermittent, intravenous administration if BM 21.0955 (2.0 mg every 3 months) during 12 months’ treatment of corticosteroid-induced osteoporosis.

Fast Facts:

Protocol number:	MF 4375
Sponsor:	Roche Global Development
Company division:	Pharmaceutical
Product name:	Bonviva/Boniva
Generic name:	ibandronate
Phase of development:	II
Therapeutic area, approved indication:	Osteoporosis
Date of report:	8/1/2000

Clinical study summary:
This was an open-label, single-arm, multicenter study in patients undergoing corticosteroid therapy. All patients received intermittent iv Bonviva, and changes in BMD and bone markers were measured.

Study center(s) :
This study was conducted in 2 sites in Germany and Switzerland.

Objectives:
To evaluate the safety and anti-resorptive efficacy of intermittent intravenous administration of Bonviva (ibandronate) in the treatment of patients undergoing corticoid therapy, as evaluated by the change in lumbar spine bone mineral density and biochemical bone markers.

Methodology:
A total of 27 patients were included in the study; all received intermittent iv Bonviva. Patients were concomitantly treated with calcium and Vitamin D. BMD measurements as well as laboratory efficacy and safety assessments were performed every 3 months. Adverse events were collected continuously throughout the trial.

Number of patients (planned/analyzed):
Planned: 25 patients. Enrolled: 27 patients.

Diagnosis and main criteria for inclusion:

Diagnosis: corticosteroid-induced osteoporosis.
Inclusion criteria: Male or female patients between 20 and 74 years of age; initiating long-term corticosteroid therapy with an initial dose of ≥15 mg/day prednisone and lumbar spine BMD ≤-1.5 SD T-score or continuing long-term corticosteroid therapy with a maintenance dose ≥7.5 mg/day prednisone and lumbar spine BMD ≤-2 SD T-score; written informed consent.

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

Duration of treatment:
1 year.

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] after 1 year of treatment compared to baseline.

Secondary: BMD of distal forearm and proximal femur; excretion of urinary CTX, NTX, calcium, pyridinoline and deoxypyridinoline; serum concentration of osteocalcin, parathyroid hormone, 25(OH) vitamin D, 1,25(OH)₂ vitamin D, total alkaline phosphatase.

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

Statistical methods:
Data were summarized using descriptive statistics. Only an abbreviated analysis of the efficacy data was performed.

Summary (efficacy, safety, other results):
Efficacy: The total lumbar spine BMD showed a mean increase of 4.68 % relative to baseline over the 12-month period of the study. The change in BMD varied substantially between individual patients.

Safety: The intravenous administration of 2.0 mg Bonviva was well tolerated over the 12-month period of the study. Few patients experienced an AE which was assessed as being possibly or probably related to the study medication. The most commonly reported AEs were asthma (14.8%) and bone pain (11.1%). Hypocalcemia, bone pain and pruritus were each assessed for one patient as being related to the study medication. One patient was prematurely withdrawn from the study due to an AE (bone pain), assessed as related to the study medication.
None of the serious adverse events (SAEs) reported during the study were assessed as related to the study medication and no patient withdrew from the study due to an SAE. The most commonly reported SAEs were asthma (4, 14.8%) and osteoporotic fracture (2, 7.4%). All other SAEs were reported no more than once. One patient died during the study as a result of terminal respiratory insufficiency. The death was attributed to the patient’s basic disease condition and the event was considered to be unrelated to the study treatment. Decreases in serum phosphate resulted in the highest incidence of marked laboratory abnormalities (8, 29.6%). No clinically relevant changes in laboratory safety parameters were observed.

Conclusions:
The results from this study indicate that 2.0 mg Bonviva increased lumbar spine BMD and was well tolerated by patients being treated for corticosteroid-induced osteoporosis when administered intravenously at 3-month intervals over a period of 1 year.