Conditions: Fractures, Bone
Keywords: GSK2371746 Denosumab China skeletal-related events bone metastases bridging study solid tumors
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 487
Healthy volunteers: no

Brief summary:
This is a randomized, double-blind, double-dummy study designed to provide bridging data in an Asian population to Amgen's studies of denosumab in subjects with bone metastases from solid tumors. The study is designed to provide data to a large global dataset of phase-III studies including breast cancer, prostate cancer, and all solid tumors, plus multiple myeloma, to support the regulatory approval for marketing and patient access to denosumab for the prevention of SREs in Chinese subjects with bone metastases from solid tumors. The primary objective of this study is to evaluate and compare the percent change from baseline to Week 13 in the bone marker urinary amino-terminal cross-linking telopeptide of type I collagen (uNTx) corrected for urine creatinine (uNTx/uCr) in subjects treated with denosumab to those treated with zoledronic acid. The study is designed to test the superiority of denosumab over zoledronic acid.

Detailed description:

Arms:
arm 1: Subjects will be administered with Denosumab 120 mg subcutaneous (SC) injection for a maximum of 13 doses and placebo IV infusion over \&gt;=15 minutes once every 4 weeks. arm 2: Subjects will be administered with Zoledronic acid 4 mg IV infusion over a minimum of 15 minutes for a maximum of 13 doses and placebo SC once every 4 weeks.

Interventions: intervention 1: Denosumab 70 mg/mL intervention 2: Zoledronic acid 4 mg intervention 3: Placebo IV intervention 4: Placebo SC intervention 5: Calcium supplement intervention 6: Vitamin D supplement
Intervention descriptions: intervention 1: Denosumab will be given as a SC injection of 120 mg by administering a 1.7 mL volume in a single injection intervention 2: Zoledronic acid 4 mg (or equivalent clearance-adjusted dose in subjects with baseline creatinine clearance \<=60 ml/min) will be diluted in either 0.9% sodium chloride or 5% dextrose injection and administered IV. intervention 3: The placebo will consist of 1.7 mL 0.9% w/v sodium chloride intervention 4: The placebo will consist of either 0.9% w/v sodium chloride or 5% dextrose injection intervention 5: Subjects are strongly recommended to take daily supplements of at least 500 mg calcium from the day of consent and until completion of the Week 73 follow-up visit. intervention 6: Subjects are strongly recommended to take daily supplements of at least 400 IU of vitamin D from the day of consent and until completion of the Week 73 follow-up visit.

Protocol document: