Continuous Erythropoietin Receptor Activator (C.E.R.A.) administered at extended administration intervals corrects anaemia in patients with chronic kidney disease on dialysis: a randomised, multicentre, multiple-dose, phase II study.
This dose-finding, open-label study examined the potential of subcutaneous Continuous Erythropoietin Receptor Activator (C.E.R.A.) to correct anaemia at extended administration intervals in 61 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease (CKD) on dialysis. After a 4-week run-in, patients were randomised to C.E.R.A. 0.15, 0.30 and 0.45 microg/kg/week. Within these dose groups, patients were further randomised to once weekly, once every 2 weeks or once every 3 weeks treatment. Mean changes in haemoglobin (Hb) increased with increasing C.E.R.A. dose during a period of 6 weeks where no dose adjustments were permitted. The effect was independent of administration schedule. Erythropoietic responses were sustained until the end of the study (12 weeks) in all groups. In total, 90% of patients in the 0.30 microg/kg/week group and 79% in the 0.45 microg/kg/week group responded to treatment (Hb increase > or =1.0 g/dl), compared with 72% in the 0.15 microg/kg/week group. Faster median response time was associated with increasing dose (51, 38 and 31 days, respectively) and response was unrelated to administration frequency. C.E.R.A. was generally well tolerated. Our results suggest that 0.60 microg/kg twice monthly would be a suitable starting dose of C.E.R.A. for the initiation of anaemia correction in patients with CKD on dialysis. Phase III studies will confirm the feasibility of using C.E.R.A. at extended administration intervals in patients with CKD and anaemia.
de Francisco
A L M
AL
Servicio de Nefrologia, Hospital Marques de Valdecilla, Santander, Spain. martinal@unican.es
Sulowicz
W
W
Klinger
M
M
Niemczyk
S
S
Vargemezis
V
V
Metivier
F
F
Dougherty
F C
FC
Oguey
D
D
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000379:methods*; D016896:Treatment Outcome
D006454:Hemoglobins; D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols