title: A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 for maintenance 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 of WBC cystine level was 0.62±0.05 nmol 1/2 cystine/mg protein after 12 hours under RP103 and 0.54±0.05 nmol 1/2 cystine/mg protein after 6 hours under Cystagon, a difference of 0.08±0.04 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.
authors.affiliation: Division of Kidney Diseases, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA. c-langman@northwestern.edu
authors.forename: Craig B
authors.initials: CB
authors.lastname: Langman
authors.forename: Larry A
authors.initials: LA
authors.lastname: Greenbaum
authors.forename: Minnie
authors.initials: M
authors.lastname: Sarwal
authors.forename: Paul
authors.initials: P
authors.lastname: Grimm
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cornelissen
authors.forename: Denis
authors.initials: D
authors.lastname: Morin
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.forename: Debora
authors.initials: D
authors.lastname: Matossian
authors.forename: Segolene
authors.initials: S
authors.lastname: Gaillard
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Bagger
authors.forename: Patrice
authors.initials: P
authors.lastname: Rioux
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018592:Cross-Over Studies; D003543:Cysteamine / Q000008:administration & dosage*; D003553:Cystine / Q000032:analysis* / Q000378:metabolism; D003554:Cystinosis / Q000188:drug therapy* / Q000378:metabolism; D003692:Delayed-Action Preparations; D005198:Fanconi Syndrome; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D003553:Cystine; D003543:Cysteamine