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 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.
RCT Entities:
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 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: Robert Kleta; Isa Bernardini; Masako Ueda; William S Varade; Chanika Phornphutkul; Donna Krasnewich; William A Gahl Journal: J Pediatr Date: 2004-10 Impact factor: 4.406
Authors: Martine T P Besouw; Richard Bowker; Jean-Paul Dutertre; Francesco Emma; William A Gahl; Marcella Greco; Marc R Lilien; John McKiernan; François Nobili; Jerry A Schneider; Flemming Skovby; Lambertus P van den Heuvel; William G Van't Hoff; Elena N Levtchenko Journal: J Pediatr Date: 2011-07-23 Impact factor: 4.406
Authors: P K Smith; R I Krohn; G T Hermanson; A K Mallia; F H Gartner; M D Provenzano; E K Fujimoto; N M Goeke; B J Olson; D C Klenk Journal: Anal Biochem Date: 1985-10 Impact factor: 3.365
Authors: Thurid Ahlenstiel-Grunow; Nele K Kanzelmeyer; Kerstin Froede; Martin Kreuzer; Jens Drube; Christian Lerch; Lars Pape Journal: Pediatr Nephrol Date: 2016-06-27 Impact factor: 3.714
Authors: Jessica Kaufeld; Lutz T Weber; Christine Kurschat; Sima Canaan-Kuehl; Eva Brand; Jun Oh; Lars Pape Journal: Internist (Berl) Date: 2018-08 Impact factor: 0.743
Authors: Jeffrey B Schwimmer; Joel E Lavine; Laura A Wilson; Brent A Neuschwander-Tetri; Stavra A Xanthakos; Rohit Kohli; Sarah E Barlow; Miriam B Vos; Saul J Karpen; Jean P Molleston; Peter F Whitington; Philip Rosenthal; Ajay K Jain; Karen F Murray; Elizabeth M Brunt; David E Kleiner; Mark L Van Natta; Jeanne M Clark; James Tonascia; Edward Doo Journal: Gastroenterology Date: 2016-08-26 Impact factor: 22.682
Authors: Francesco Emma; Galina Nesterova; Craig Langman; Antoine Labbé; Stephanie Cherqui; Paul Goodyer; Mirian C Janssen; Marcella Greco; Rezan Topaloglu; Ewa Elenberg; Ranjan Dohil; Doris Trauner; Corinne Antignac; Pierre Cochat; Frederick Kaskel; Aude Servais; Elke Wühl; Patrick Niaudet; William Van't Hoff; William Gahl; Elena Levtchenko Journal: Nephrol Dial Transplant Date: 2014-09 Impact factor: 5.992