title: A single-dose study of denosumab in patients with various degrees of renal impairment.
abstract: This 16-week study evaluated pharmacokinetics and pharmacodynamics of denosumab in 55 subjects with renal function ranging from normal to dialysis-dependent kidney failure. Participants received a single 60-mg subcutaneous dose of denosumab. Kidney function groups were based on calculations using the Cockcroft-Gault equation and U.S. Food and Drug Administration (FDA) guidance in place when the study was designed. Renal function did not have a significant effect on denosumab pharmacokinetics or pharmacodynamics. These findings suggest denosumab dose adjustment based on glomerular filtration rate is not required. Rapid decreases in serum C-telopeptide in all groups were sustained throughout the study. The most common adverse events were hypocalcemia (15%), pain in extremity (15%), and nausea (11%). Most adverse events were mild to moderate in severity. Calcium and vitamin D supplementation was not initially required by the study protocol, but was added during the trial. No subject who received adequate calcium and vitamin D supplementation became hypocalcemic. Seven subjects had nadir serum calcium concentrations between 7.5 and <8.0 mg/dL (1.9 and <2.0 mmol/L), and 5 subjects (4 with advanced renal disease) had nadir serum calcium <7.5 mg/dL (<1.9 mmol/L). Two subjects (1 symptomatic, 1 asymptomatic) were hospitalized for intravenous calcium gluconate treatment. At the recommended dose, denosumab is a useful therapeutic option for patients with impaired renal function. Supplementation of calcium and vitamin D is strongly recommended when patients initiate denosumab therapy, particularly in patients with reduced renal function.
authors.affiliation: Denver Nephrologists, PC, Clinical Research Division, Denver, CO, USA.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.forename: Henry G
authors.initials: HG
authors.lastname: Bone
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.forename: Edward
authors.initials: E
authors.lastname: Lee
authors.forename: Desmond
authors.initials: D
authors.lastname: Padhi
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D002118:Calcium / Q000378:metabolism; D002125:Calcium Gluconate / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D000069448:Denosumab; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000188:drug therapy*; D014481:United States; D014486:United States Food and Drug Administration; D014807:Vitamin D / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D014807:Vitamin D; D000069448:Denosumab; D002125:Calcium Gluconate; D002118:Calcium