A Single-Dose Placebo-Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal Women
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- Pirow J Bekker
- Amgen Inc., Thousand Oaks, California, USA
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- Donna L Holloway
- Amgen Inc., Thousand Oaks, California, USA
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- Amy S Rasmussen
- Amgen Inc., Thousand Oaks, California, USA
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- Robyn Murphy
- Amgen Inc., Thousand Oaks, California, USA
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- Steven W Martin
- Amgen Inc., Thousand Oaks, California, USA
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- Philip T Leese
- Quintiles, Lenexa, Kansas, USA
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- Gregory B Holmes
- SFBC International, Inc., Miami, Florida, USA
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- Colin R Dunstan
- ANZAC Research Institute, Concord, New South Wales, Australia
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- Alex M DePaoli
- Amgen Inc., Thousand Oaks, California, USA
抄録
<jats:title>Abstract</jats:title> <jats:p>The safety and bone antiresorptive effect of a single subcutaneous dose of AMG 162, a human monoclonal antibody to RANKL, was investigated in 49 postmenopausal women. AMG 162 is a potent antiresorptive agent for diseases such as osteoporosis.</jats:p> <jats:p>Introduction: RANKL is an essential osteoclastic differentiation and activation factor.</jats:p> <jats:p>Materials and Methods: The bone antiresorptive activity and safety of AMG 162, a fully human monoclonal antibody to RANKL, were evaluated in postmenopausal women in this randomized, double-blind, placebo-controlled, single-dose, dose escalation study. Six cohorts of eight to nine women were randomly assigned to receive a single subcutaneous injection of either AMG 162 or placebo (3:1 ratio). AMG 162 doses were 0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. Subjects were followed up to 6 months in all cohorts and 9 months in the three highest dose cohorts. Second morning void urinary N-telopeptide/creatinine (NTX; Osteomark), serum NTX, and serum bone-specific alkaline phosphatase (BALP, Ostase) were assessed as bone turnover markers.</jats:p> <jats:p>Results and Conclusions: Forty-nine women were enrolled. A single subcutaneous dose of AMG 162 resulted in a dose-dependent, rapid (within 12 h), profound (up to 84%), and sustained (up to 6 months) decrease in urinary NTX. At 6 months, there was a mean change from baseline of −81% in the 3.0 mg/kg AMG 162 group compared with −10% in the placebo group; serum NTX changes were −56% and 2%, respectively. BALP levels did not decrease remarkably until after 1 month, indicating that the effect of AMG 162 is primarily antiresorptive. Intact parathyroid hormone (PTH) levels increased up to ∼3-fold after 4 days in the 3.0 mg/kg dose group, but returned toward baseline with follow-up. Albumin-adjusted serum calcium did not decrease >10% on average in any group, and no subject had values below 2 mmol/liter. AMG 162 was well tolerated. No related serious adverse events occurred. No clinically meaningful laboratory changes, other than those described above, were observed. In summary, a single subcutaneous dose of AMG 162 resulted in a dose-dependent rapid and sustained decrease from baseline in bone turnover and could be an effective and convenient treatment for osteoporosis.</jats:p>
収録刊行物
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- Journal of Bone and Mineral Research
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Journal of Bone and Mineral Research 19 (7), 1059-1066, 2004-07-01
Oxford University Press (OUP)
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詳細情報 詳細情報について
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- CRID
- 1362825893270657408
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- NII論文ID
- 30021656344
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- ISSN
- 15234681
- 08840431
- http://id.crossref.org/issn/08840431
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- データソース種別
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- Crossref
- CiNii Articles