Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis
Condition: Cystinosis
MeSH terms: Cystinosis
Intervention: RP103
Intervention description: Cysteamine Bitartrate Delayed-release Capsules (RP103) were administered twice daily, orally or via gastrostomy tube (G-tube), after a 2-hour fast. The starting dose was one-quarter of the RP103 targeted maintenance dose based on age, weight, and body surface area. The recommended targeted maintenance dose for children up to 6 years old was 1 gram/m²/day, in 2 divided doses given Q12H. The dose was gradually escalated, in 10% steps, based on monitoring of WBC cystine levels 30 minutes after the morning RP103 dose collected every 2 weeks, until the participant's WBC cystine level was <1 nmol ½ cystine/mg protein.
Intervention MeSH terms: Cysteamine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Maximum age: 6 Years
Healthy volunteers: No
Keywords: Nephropathic Cystinosis; Cysteamine; Delayed-release Cysteamine; CTNS Protein, Human; Orphan Disease

Summary:

      This was a long-term, open-label study of the safety, tolerability and effectiveness of RP103
      in cystinosis patients who were naïve to any form of cysteamine treatment. Participants
      received RP103 treatment for at least 12 months. U.S. participants transitioned to the
      commercially approved drug PROCYSBI®. In Brazil, after at least 12 months of study
      participation and upon approval by the Brazilian regulatory authorities, participants were
      eligible to transition to a post-study drug supply program, and continue to receive the drug
      at no personal cost.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female with a documented diagnosis of cystinosis

          -  No clinically significant change in liver function tests, i.e. 1.5 times upper limit
             of normal (ULN) for alanine aminotransferase (ALT) and aspartate aminotransferase
             (AST), and/or 1.5 times ULN for total bilirubin, within 6 months prior to Screening

          -  No clinically significant change in renal function, i.e. estimated glomerular
             filtration rate (GFR) within 6 months prior to Screening

          -  Must have an estimated GFR > 20 mL/minute/1.73m² (using the equation from Schwartz
             2009 J Am Soc Nephrol 20:629-647)

          -  Female participants who are sexually active and of childbearing potential, i.e. not
             surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy) or at
             least 2 years naturally postmenopausal must agree to use an acceptable form of
             contraception from Screening through completion of the study. Acceptable forms of
             contraception for this study include hormonal contraceptives (oral, implant,
             transdermal patch, or injection) at a stable dose for at least 3 months prior to
             Screening, barrier (spermicidal condom or diaphragm with spermicide), IUD, or a
             partner who has been vasectomized for at least 6 months. Childbearing potential was
             defined as a female who had reached menarche.

          -  Participant or their parent or guardian must provide written informed consent and
             assent (where applicable) prior to participation in the study

          -  Had not taken any form of cysteamine bitartrate in the past

        Exclusion Criteria:

          -  Current history of the following conditions or any other health issues that make it,
             in the opinion of the Investigator, unsafe for study participation:

          -  Inflammatory bowel disease if currently active, or prior resection of the small
             intestine

          -  Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias, or
             poorly controlled hypertension) within 90 days prior to Screening

          -  Active bleeding disorder within 90 days prior to Screening

          -  History of malignant disease within 2 years prior to Screening

          -  Hemoglobin level of < 10 g/dL at Screening or, in the opinion of the investigator, a
             hemoglobin level that would make it unsafe for study participation

          -  Known hypersensitivity to penicillamine

          -  Female subjects who were nursing, planning a pregnancy, or were known or suspected to
             be pregnant

          -  Participants who, in the opinion of the investigator, were not able or willing to
             comply with study requirements

          -  Had received a kidney transplant or was currently on dialysis

          -  Was 6 years of age or older at the time of the Screening visit