Literature DB >> 21940838

Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients.

Iain C Macdougall1, Andrzej Wiecek, Beatriz Tucker, Magdi Yaqoob, Ashraf Mikhail, Michal Nowicki, Iain MacPhee, Michal Mysliwiec, Olgierd Smolenski, Władysław Sułowicz, Martha Mayo, Carol Francisco, Krishna R Polu, Peter J Schatz, Anne-Marie Duliege.   

Abstract

BACKGROUND AND OBJECTIVES: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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.

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Year:  2011        PMID: 21940838      PMCID: PMC3359570          DOI: 10.2215/CJN.10831210

Source DB:  PubMed          Journal:  Clin J Am Soc Nephrol        ISSN: 1555-9041            Impact factor:   8.237


  17 in total

1.  European best practice guidelines 6-8: assessing and optimizing iron stores.

Authors:  I C Macdougall; W H Hörl; C Jacobs; F Valderrábano; I Parrondo; K Thompson; S Cremers
Journal:  Nephrol Dial Transplant       Date:  2000       Impact factor: 5.992

2.  Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure.

Authors:  Francesco Locatelli; Pedro Aljama; Peter Bárány; Bernard Canaud; Fernando Carrera; Kai-Uwe Eckardt; Walter H Hörl; Iain C Macdougal; Alison Macleod; Andrzej Wiecek; Stewart Cameron
Journal:  Nephrol Dial Transplant       Date:  2004-05       Impact factor: 5.992

3.  The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. Cooperative Multicenter EPO Clinical Trial Group.

Authors:  R W Evans; B Rader; D L Manninen
Journal:  JAMA       Date:  1990-02-09       Impact factor: 56.272

4.  Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients.

Authors:  Yves Vanrenterghem; Peter Bárány; Johannes F E Mann; Peter G Kerr; Janet Wilson; Nigel F Baker; Stephen J Gray
Journal:  Kidney Int       Date:  2002-12       Impact factor: 10.612

5.  Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment of anemia in hemodialysis patients.

Authors:  Anatole Besarab; Carolina M Reyes; John Hornberger
Journal:  Am J Kidney Dis       Date:  2002-09       Impact factor: 8.860

Review 6.  The effect of anemia treatment on selected health-related quality-of-life domains: a systematic review.

Authors:  Susan D Ross; Kyle Fahrbach; Diana Frame; Rachel Scheye; Janet E Connelly; John Glaspy
Journal:  Clin Ther       Date:  2003-06       Impact factor: 3.393

7.  A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia.

Authors:  Iain C Macdougall; Jerome Rossert; Nicole Casadevall; Richard B Stead; Anne-Marie Duliege; Marc Froissart; Kai-Uwe Eckardt
Journal:  N Engl J Med       Date:  2009-11-05       Impact factor: 91.245

8.  Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo).

Authors:  Francesco Locatelli; Bernard Canaud; Francis Giacardy; Alejandro Martin-Malo; Nigel Baker; Janet Wilson
Journal:  Nephrol Dial Transplant       Date:  2003-02       Impact factor: 5.992

9.  Darbepoetin alfa effectively maintains haemoglobin concentrations at extended dose intervals relative to intravenous or subcutaneous recombinant human erythropoietin in dialysis patients.

Authors:  Reinhard Brunkhorst; Jürgen Bommer; Johann Braun; Marianne Haag-Weber; Caroline Gill; Jürgen Wagner; Thomas Wagener
Journal:  Nephrol Dial Transplant       Date:  2004-02-19       Impact factor: 5.992

10.  Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial.

Authors:  J W Eschbach; M H Abdulhadi; J K Browne; B G Delano; M R Downing; J C Egrie; R W Evans; E A Friedman; S E Graber; N R Haley
Journal:  Ann Intern Med       Date:  1989-12-15       Impact factor: 25.391

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  11 in total

1.  Anaemia: The safety and efficacy of peginesatide in patients with CKD.

Authors:  Kai-Uwe Eckardt
Journal:  Nat Rev Nephrol       Date:  2013-03-12       Impact factor: 28.314

Review 2.  Management of anemia with erythropoietic-stimulating agents in children with chronic kidney disease.

Authors:  Bradley A Warady; Douglas M Silverstein
Journal:  Pediatr Nephrol       Date:  2013-09-05       Impact factor: 3.714

Review 3.  Peginesatide for the treatment of anemia due to chronic kidney disease - an unfulfilled promise.

Authors:  Terhi Hermanson; Charles L Bennett; Iain C Macdougall
Journal:  Expert Opin Drug Saf       Date:  2016-08-23       Impact factor: 4.250

4.  Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal Dialysis.

Authors:  Raja Zabaneh; Simon D Roger; Mohamed El-Shahawy; Michael Roppolo; Grant Runyan; Janet O'Neil; Ping Qiu
Journal:  Perit Dial Int       Date:  2014-03-01       Impact factor: 1.756

Review 5.  Differentiating factors between erythropoiesis-stimulating agents: an update to selection for anaemia of chronic kidney disease.

Authors:  Walter H Hörl
Journal:  Drugs       Date:  2013-02       Impact factor: 9.546

6.  An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients.

Authors:  Anatole Besarab; Steven N Zeig; Edouard R Martin; Pablo E Pergola; Frederick C Whittier; Raja I Zabaneh; Brigitte Schiller; Martha Mayo; Carol A Francisco; Krishna R Polu; Anne-Marie Duliege
Journal:  BMC Nephrol       Date:  2012-08-30       Impact factor: 2.388

Review 7.  Managing dialysis patients who develop anemia caused by chronic kidney disease: focus on peginesatide.

Authors:  Amanda Valliant; R Michael Hofmann
Journal:  Int J Nanomedicine       Date:  2013-08-26

8.  Profile of peginesatide and its potential for the treatment of anemia in adults with chronic kidney disease who are on dialysis.

Authors:  Ashraf Mikhail
Journal:  J Blood Med       Date:  2012-05-23

9.  A Population Pharmacokinetic and Pharmacodynamic Analysis of Peginesatide in Patients with Chronic Kidney Disease on Dialysis.

Authors:  Himanshu Naik; Max C Tsai; Jill Fiedler-Kelly; Ping Qiu; Majid Vakilynejad
Journal:  PLoS One       Date:  2013-06-19       Impact factor: 3.240

10.  Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients.

Authors:  Anatole Besarab; Robert Provenzano; Joachim Hertel; Raja Zabaneh; Stephen J Klaus; Tyson Lee; Robert Leong; Stefan Hemmerich; Kin-Hung Peony Yu; Thomas B Neff
Journal:  Nephrol Dial Transplant       Date:  2015-08-03       Impact factor: 5.992

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