Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects

Nephrology Dialysis Transplantation

Volumn 29, Issue 2, 2014, Pages 385-392

  Martin, Kevin J ^a   Bell, Gregory ^b   Pickthorn, Karen ^b   Huang, Saling ^b   Vick, Andrew ^c   Hodsman, Peter ^d   Peacock, Munro ^e  

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

^b AMGEN INC   (United States)

^c Seventh Wave Laboratories LLC   (United States)

^d Nucleus Network Ltd   (Australia)

^e INDIANA UNIVERSITY   (United States)

Author keywords

AMG 416; calcimimetic; FGF23; parathyroid hormone; velcalcetide

Indexed keywords

CALCITONIN; CALCITRIOL; CALCIUM; CALCIUM ION; CALCIUM SENSING RECEPTOR; CREATININE; FIBROBLAST GROWTH FACTOR 23; PARATHYROID HORMONE; PHOSPHORUS; PLACEBO; SODIUM CHLORIDE; VELCALCETIDE;

ABDOMINAL DISCOMFORT; ADULT; AREA UNDER THE CURVE; ARTICLE; CALCITONIN BLOOD LEVEL; CALCIUM BLOOD LEVEL; CHEMICAL ANALYSIS; COHORT ANALYSIS; CONTROLLED STUDY; CREATININE URINE LEVEL; DIARRHEA; DISTRIBUTION VOLUME; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; HEMATOLOGICAL PARAMETERS; HOT FLUSH; HUMAN; HUMAN EXPERIMENT; KIDNEY TUBULE ABSORPTION; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; PARATHYROID HORMONE BLOOD LEVEL; PARESTHESIA; PHASE 1 CLINICAL TRIAL; PHOSPHATE BLOOD LEVEL; PHOSPHATE EXCRETION; PLASMA CLEARANCE; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TREATMENT OUTCOME; VITAL SIGN; VITAMIN BLOOD LEVEL; VOMITING;

AMG 416; CALCIMIMETIC; FGF23; PARATHYROID HORMONE; VELCALCETIDE;

ADOLESCENT; ADULT; BIOLOGICAL MARKERS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FIBROBLAST GROWTH FACTORS; FOLLOW-UP STUDIES; HUMANS; HYPERPARATHYROIDISM, SECONDARY; INJECTIONS, INTRAVENOUS; MALE; MIDDLE AGED; PARATHYROID HORMONE; PEPTIDES; RECEPTORS, CALCIUM-SENSING; REFERENCE VALUES; RENAL INSUFFICIENCY, CHRONIC; RENAL OSTEODYSTROPHY; TIME FACTORS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84896704224     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gft417     Document Type: Article

References (30)

1. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: Pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011; 6: 913-921
2. Drueke T, Martin D, Rodriguez M. Can calcimimetics inhibit parathyroid hyperplasia?. Evidence from preclinical studies. Nephrol Dial Transplant 2007; 22: 1828-1839
3. Goodman WG. The consequences of uncontrolled secondary hyperparathyroidism and its treatment in chronic kidney disease. Semin Dial 2004; 17: 209-216
4. Nemeth EF, Heaton WH, Miller M et al. Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. J Pharmacol Exp Ther 2004; 308: 627-635
5. Block GA, Martin KJ, de Francisco AL et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004; 350: 1516-1525
6. Brown EM, Gamba G, Riccardi D et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 1993; 366: 575-580
7. Brown EM, Pollak M, Hebert SC. The extracellular calcium-sensing receptor: Its role in health and disease. Annu Rev Med 1998; 49: 15-29
8. Gincherman Y, Moloney K, McKee C et al. Assessment of adherence to cinacalcet by prescription refill rates in hemodialysis patients. Hemodial Int 2010; 14: 68-72
9. 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: 229-240
10. Peacock M. Primary hyperparathyroidism and the kidney: Biochemical and clinical spectrum. J Bone Miner Res 2002; 17(Suppl. 2): N87-N94
11. Fekedulegn DB, Andrew ME, Burchfiel CM et al. Area under the curve and other summary indicators of repeated waking cortisol measurements. Psychosom Med 2007; 69: 651-659
12. Shoback DM, Bilezikian JP, Turner SA et al. The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism. J Clin EndocrinolMetab 2003; 88: 5644-5649
13. Peacock M, Bilezikian JP, Klassen PS et al. Cinacalcet hydrochloride maintains long-Term normocalcemia in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 2005; 90: 135-141
14. Saito G, Swanson JA, Lee KD. Drug delivery strategy utilizing conjugation via reversible disulfide linkages: Role and site of cellular reducing activities. Adv Drug Deliv Rev 2003; 55: 199-215
15. Yamashita T, Konishi M, Miyake A et al. Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-Activated protein kinase pathway. J Biol Chem 2002; 277: 28265-28270
16. Chonchol M, Locatelli F, Abboud HE et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis. Am J Kidney Dis 2009; 53: 197-207
17. Sato T, Tominaga Y, Ueki T et al. Total parathyroidectomy reduces elevated circulating fibroblast growth factor 23 in advanced secondary hyperparathyroidism. Am J Kidney Dis 2004; 44: 481-487
18. 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: 784-790
19. 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: 110-116
20. Finch JL, Tokumoto M, Nakamura H et al. Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease. Am J Physiol Renal Physiol 2010; 298: F1315-F1322
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: 2600-2608
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: 948-955
23. Faul C, Amaral AP, Oskouei B et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011; 121: 4393-4408
24. Gutierrez OM, Januzzi JL, Isakova T et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 2009; 119: 2545-2552
25. Gutierrez OM, Mannstadt M, Isakova T et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359: 584-592
26. Shimada T, Kakitani M, Yamazaki Y et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 2004; 113: 561-568
27. Padhi D, Harris R. Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet 2009; 48: 303-311
28. Martin KJ, Pickthorn K, Huang S et al. AMG 416 (velcalcetide) is a novel peptide for the treatment of secondary hyperparathyroidism in a singledose study in hemodialysis patients. Kidney Int 2013; doi:10.1038/ ki.2013.289
29. Mudo G, Trovato-Salinaro A, Barresi V et al. Identification of calcium sensing receptor (CaSR) mRNA-expressing cells in normal and injured rat brain. Brain Res 2009; 1298: 24-36
30. Yano S, Brown EM, Chattopadhyay N. Calcium-sensing receptor in the brain. Cell Calcium 2004; 35: 257-264