title: Subcutaneous injection pain with C.E.R.A., a continuous erythropoietin receptor activator, compared with darbepoetin alfa.
abstract: OBJECTIVE
  This study assessed injection site pain following subcutaneous (SC) administration with a continuous erythropoietin receptor activator (C.E.R.A.), compared with darbepoetin alfa in healthy adults.
  
  
  METHODS
  In a randomized, placebo-controlled, single-centre, single-blind, three-way crossover study, subjects received one of six treatment sequences (ABC/ACB/BAC/BCA/CBA/CAB) involving SC injection of (A) C.E.R.A. 50 microg, (B) darbepoetin alfa 50 microg, or (C) placebo on days 1, 29, and 57. An initial pilot phase (n = 12) was used to determine the sample size for the confirmatory phase (n = 72), and data were combined for the final analysis (n = 84).
  
  
  METHODS
  The primary endpoint was pain on the 100 mm visual analog scale (VAS) immediately after dosing. Secondary endpoints included VAS at 1 hour after dosing and pain on the six-point verbal rating scale (VRS) immediately and at 1 hour after dosing.
  
  
  RESULTS
  C.E.R.A. was associated with significantly less pain immediately after SC injection compared with darbepoetin alfa: least squares mean VAS 21.5 (95% confidence interval [CI]: 17.5, 25.5) versus 33.4 (95% CI: 28.4, 38.4) (p < 0.0001). Incidence of pain on the VRS was lower with C.E.R.A. compared with darbepoetin alfa immediately after dosing (p < 0.0001). One hour after administration, most subjects had no VRS pain. A study limitation is the small sample size and the findings need to be confirmed in a large trial of chronic kidney disease patients.
  
  
  CONCLUSIONS
  SC injection with C.E.R.A. is significantly less painful than SC darbepoetin alfa in healthy adults. Treatment of anemia in chronic kidney disease with SC injection of C.E.R.A. may provide a lower pain burden compared with darbepoetin alfa.
authors.affiliation: Roche, Basel, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Pannier
authors.forename: Paul
authors.initials: P
authors.lastname: Jordan
authors.forename: Frank C
authors.initials: FC
authors.lastname: Dougherty
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bour
authors.forename: Bruno
authors.initials: B
authors.lastname: Reigner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000175:diagnosis / Q000209:etiology; D010147:Pain Measurement; D010919:Placebos; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects*; D011994:Recombinant Proteins
chemical_list: D006397:Hematinics; D010919:Placebos; D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D011092:Polyethylene Glycols