A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: Effectiveness on white blood cell cystine levels and comparison of safety

Craig B. Langman, Larry A. Greenbaum, Minnie Sarwal, Paul Grimm, Patrick Niaudet, Georges Deschênes, Elisabeth Cornelissen, Denis Morin, Pierre Cochat, Debora Matossian, Segolene Gaillard, Mary Jo Bagger, Patrice Rioux

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Background and objectives Immediate-release cysteamine bitartrate (Cystagon; Mylan Pharmaceuticals, Canonsburg, PA) may prevent or delay kidney transplantation and other serious outcomes in patients with cystinosis, but has never been subjected to a prospective clinical trial. Cystagon efficacy requires strict lifelong dosing every 6 hours. Such a dosing schedule and Cystagon-associated side effects are often cited by patients as reasons for nonadherence. Design, setting, participants, & measurements This open-label, randomized, controlled, crossover trial was powered to show that a new delayed-release formulation of cysteamine bitartrate, RP103, taken every 12 hours, was noninferior to Cystagon formaintenance of white blood cell (WBC) cystine at levels associated with optimal outcomes in the disease. Results Forty-three patients were randomized. Using a mixed-effects statistical analysis model, the least-squares mean peak value ofWBC cystine level was 0.6260.05 nmol 1/2 cystine/mg protein after 12 hours under RP103 and 0.5460.05 nmol 1/2 cystine/mg protein after 6 hours under Cystagon, a difference of 0.0860.04 nmol 1/2 cystine/mg protein (95.8% confidence interval, 0-0.16). The average steady-state total daily dose of RP103 was 82% of the incoming steady-state total daily dose of Cystagon. There were three-fold more gastrointestinal side effects compared with using Cystagon. Conclusions A new delayed-release Q12H formulation of cysteamine bitartrate is not inferior to the Q6H formulation (Cystagon) in maintaining low WBC cystine levels in patients with cystinosis but at a lower total daily dose.

Original languageEnglish (US)
Pages (from-to)1112-1120
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume7
Issue number7
DOIs
StatePublished - Jul 1 2012

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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