A randomized, double-blind, phase 2 study evaluating the safety and efficacy of AMG 416 for the treatment of secondary hyperparathyroidism in hemodialysis patients

Current Medical Research and Opinion

Volumn 31, Issue 5, 2015, Pages 943-952

  Bell, Gregory ^a,b   Huang, Saling ^a   Martin, Kevin J ^c   Block, Geoffrey A ^d  

^a AMGEN INC   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d Denver Nephrology   (United States)

Author keywords

AMG 416; Calcium sensing receptor; Chronic kidney disease; Hemodialysis; Secondary hyperparathyroidism

Indexed keywords

ALBUMIN; ALKALINE PHOSPHATASE; CALCIMIMETIC AGENT; CALCIUM; ETELCALCETIDE; PARATHYROID HORMONE; PHOSPHATE; PLACEBO; VITAMIN D; AMG-416; CALCIUM SENSING RECEPTOR; PEPTIDE;

ADULT; ALKALINE PHOSPHATASE BLOOD LEVEL; ANEMIA; ANXIETY; AREA UNDER THE CURVE; ARTICLE; BOLUS INJECTION; CALCIUM BLOOD LEVEL; CLINICAL ARTICLE; CLINICAL ASSESSMENT; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; END STAGE RENAL DISEASE; FEMALE; FOLLOW UP; HEMODIALYSIS; HEMODIALYSIS PATIENT; HUMAN; HYPERCALCEMIA; HYPERVOLEMIA; HYPOCALCEMIA; HYPOTENSION; LIMB PAIN; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; MUSCLE SPASM; NAUSEA; PARATHYROID HORMONE BLOOD LEVEL; PHASE 2 CLINICAL TRIAL; PHOSPHATE BLOOD LEVEL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; SECONDARY HYPERPARATHYROIDISM; SIDE EFFECT; TREATMENT DURATION; VOMITING; ADVERSE EFFECTS; AGED; AGONISTS; BLOOD; CHRONIC KIDNEY FAILURE; CLINICAL TRIAL; COMPARATIVE STUDY; COMPLICATION; HYPERPARATHYROIDISM, SECONDARY; INTRAVENOUS DRUG ADMINISTRATION; MIDDLE AGED; PROCEDURES; RENAL REPLACEMENT THERAPY;

ADULT; AGED; DOUBLE-BLIND METHOD; FEMALE; HUMANS; HYPERPARATHYROIDISM, SECONDARY; INJECTIONS, INTRAVENOUS; MALE; MIDDLE AGED; PARATHYROID HORMONE; PEPTIDES; RECEPTORS, CALCIUM-SENSING; RENAL DIALYSIS; RENAL INSUFFICIENCY, CHRONIC;

EID: 84928175505     PISSN: 03007995     EISSN: 14734877     Source Type: Journal    
DOI: 10.1185/03007995.2015.1031731     Document Type: Article

References (24)

1. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011;6:913-21
2. Drueke TB. The pathogenesis of parathyroid gland hyperplasia in chronic renal failure. Kidney Int 1995;48:259-72
3. Alem AM, Sherrard DJ, Gillen DL, et al. Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int 2000;58:396-9
4. Block GA, Spiegel DM, Ehrlich J, et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005;68:1815-24
5. Chertow GM, Burke SK, Raggi P, et al. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:245-52
6. Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011;121:4393-408
7. Hagstrom E, Ingelsson E, Sundstrom J, et al. Plasma parathyroid hormone and risk of congestive heart failure in the community. Eur J Heart Fail 2010;12:1186-92
8. Liu X, Xie R, Liu S. Rat parathyroid hormone 1-34 signals through the MEK/ ERK pathway to induce cardiac hypertrophy. J Int Med Res 2008;36:942-50
9. Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208-18
10. Ganesh SK, Stack AG, Levin NW, et al. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001;12:2131-8
11. Matsuoka M, Iseki K, Tamashiro M, et al. Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis. Clin Exp Nephrol 2004;8:54-8
12. Block GA, Martin KJ, de Francisco AL, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004; 350:1516-25
13. Nemeth EF, Heaton WH, Miller M, et al. Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. J Pharmacol Exp Ther 2004;308: 627-35
14. Koizumi M, Komaba H, Nakanishi S, et al. Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with secondary hyperparathyroidism. Nephrol Dial Transplant 2012;27:784-90
15. Walter S, Baruch A, Alexander ST, et al. Comparison of AMG 416 and cinacalcet in rodent models of uremia. BMC Nephrol 2014;15:81
16. Walter S, Baruch A, Dong J, et al. Pharmacology of AMG 416 (velcalcetide), a novel peptide agonist of the calcium-sensing receptor, for the treatment of secondary hyperparathyroidism in hemodialysis patients. J Pharmacol Exp Ther 2013;346:229-40
17. Martin KJ, Bell G, Pickthorn K, et al. Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. Nephrol Dial Transplant 2014;29:385-92
18. Martin KJ, Pickthorn K, Huang S, et al. AMG 416 (velcalcetide) is a novel peptide for the treatment of secondary hyperparathyroidism in a single-dose study in hemodialysis patients. Kidney Int 2014;85:191-7
19. Chen P, Melhem M, Xiao J, et al. Population pharmacokinetics analysis of AMG 416, an allosteric activator of the calcium-sensing receptor, in subjects with secondary hyperparathyroidism receiving hemodialysis. J Clin Pharmacol 2015: published online 8 January 2015, doi: 10.1002/jcph.460
20. National Kidney F. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42: S1-201
21. Fliser D, Kollerits B, Neyer U, et al. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol 2007;18:2600-8
22. Jean G, Bresson E, Terrat JC, et al. Peripheral vascular calcification in longhaemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 2009;24:948-55
23. Gutierrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008;359:584-92
24. Wetmore JB, Liu S, Krebill R, et al. Effects of cinacalcet and concurrent low-dose vitamin D on FGF23 levels in ESRD. Clin J Am Soc Nephrol 2010;5:110-16