title: Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients.
abstract: OBJECTIVE
  Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent. We report the first assessment of its efficacy and safety in correcting renal anemia in a population of 139 nondialysis chronic kidney disease patients.
  
  
  METHODS
  Chronic kidney disease patients who were not on dialysis and not receiving treatment with erythropoiesis-stimulating agents in the 12 weeks before study drug administration were sequentially assigned to one of 10 cohorts; cohorts differed in starting peginesatide dose (different body weight-based or absolute doses), route of administration (intravenous or subcutaneous), and frequency of administration (every 4 or 2 weeks).
  
  
  RESULTS
  Across all cohorts, 96% of patients achieved a hemoglobin response. A dose-response relationship was evident for hemoglobin increase. Comparable subcutaneous and intravenous peginesatide doses produced similar hemoglobin responses. Rapid rates of hemoglobin rise and hemoglobin excursions >13 g/dl tended to occur more frequently with every-2-weeks dosing than they did with every-4-weeks dosing. The range of final median doses in the every-4-weeks dosing groups was 0.019 to 0.043 mg/kg. Across all cohorts, 20% of patients reported serious adverse events (one patient had a possibly drug-related serious event) and 81% reported adverse events (11.5% reported possibly drug-related events); these events were consistent with those routinely observed in this patient population.
  
  
  CONCLUSIONS
  This study suggests that peginesatide administered every 4 weeks can increase and maintain hemoglobin in nondialysis chronic kidney disease patients. Additional long-term data in larger groups of patients are required to further elucidate the efficacy and safety of this peptide-based erythropoiesis-stimulating agent.
authors.affiliation: Renal Unit, King's College Hospital, London, United Kingdom. iain.macdougall@nhs.net
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macdougall
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiecek
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tucker
authors.forename: Magdi
authors.initials: M
authors.lastname: Yaqoob
authors.forename: Ashraf
authors.initials: A
authors.lastname: Mikhail
authors.forename: Michal
authors.initials: M
authors.lastname: Nowicki
authors.forename: Iain
authors.initials: I
authors.lastname: MacPhee
authors.forename: Michal
authors.initials: M
authors.lastname: Mysliwiec
authors.forename: Olgierd
authors.initials: O
authors.lastname: Smolenski
authors.forename: Władysław
authors.initials: W
authors.lastname: Sułowicz
authors.forename: Martha
authors.initials: M
authors.lastname: Mayo
authors.forename: Carol
authors.initials: C
authors.lastname: Francisco
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Polu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schatz
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Duliege
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007674:Kidney Diseases / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D011044:Poland; D012044:Regression Analysis; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D010455:Peptides; C556270:peginesatide