Phase 3 Study of Cysteamine Bitartrate Delayed-release (RP103) Compared to Cystagon® in Patients With Cystinosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Raptor Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01000961
First received: October 22, 2009
Last updated: September 17, 2012
Last verified: September 2012
  Purpose

Cystinosis is an inherited disease that if untreated, results in kidney failure as early as the first decade of life. The current marketed therapy is Cystagon® (cysteamine bitartrate) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. RP103 is a formulation of cysteamine bitartrate that is being studied to see if it may be able to be given less frequently, once every 12 hours, and have similar results to four times a day Cystagon®.


Condition Intervention Phase
Cystinosis
Drug: Cystagon® (Cysteamine Bitartrate)
Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Crossover Pharmacokinetic and Pharmacodynamic Study to Determine the Safety and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cystagon® in Patients With Nephropathic Cystinosis

Resource links provided by NLM:


Further study details as provided by Raptor Pharmaceuticals Inc.:

Primary Outcome Measures:
  • To assess the steady-state white blood cell cystine levels of RP103 compared to Cystagon® [ Time Frame: 4 weeks after the last subject has completed the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the safety and tolerability of RP103 compared to Cystagon® [ Time Frame: 4 weeks after the last subject has completed the study ] [ Designated as safety issue: Yes ]
  • To assess the steady state pharmacokinetics and pharmacodynamics of RP103 compared to Cystagon®. [ Time Frame: 4 weeks after the last subject has completed the study ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: June 2010
Study Completion Date: August 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RP103 Q12H Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103)

Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:

Every 12H, supplied in 75 and 25mg capsules/Duration of Treatment: 3 weeks

Active Comparator: Cystagon® Q6H Drug: Cystagon® (Cysteamine Bitartrate)

Run-in Period (Weeks 1, 2, 3) and Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:

Every 6H, supplied in 150 and 50mg capsules/Duration of Treatment: 3 weeks each period used


Detailed Description:

This is a multi-center, open-label, randomized, cross-over study to determine whether steady-state, twice a day treatment with Cysteamine Bitartrate Delayed-release Capsules(RP103) results in comparable depletion of white blood cell (WBC) cystine levels compared to the existing four times a day cysteamine treatment. It will involve up to 20 clinic visits plus intermittent home use of the RP103. Most of these clinic visits occur in clusters of 3-4 consecutive days. Eligible patients will be offered enrollment into a long-term follow up study.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects must have nephropathic cystinosis.
  • Subjects must be on a stable dose of Cystagon® sufficient to maintain their white blood cell (WBC) cystine level at ≤ 1.0 nmol/half-cystine/mg protein.
  • Subjects must be able to swallow their typically administered Cystagon® capsule with the capsule intact.
  • Within the last 6 months, no clinically significant change in liver function [i.e., ALT, AST, total bilirubin] and renal function [i.e., estimated GFR] at Screening as determined by the Investigator.
  • Subjects with an estimated GFR (corrected for body surface area) > 30 mL/min/1.73m2.
  • Sexually active female subjects of childbearing potential (i.e., not surgically sterile [tubal ligation, hysterectomy, or bilateral oophorectomy] or at least 2 years naturally postmenopausal) must agree to utilize the same acceptable form of contraception from Screening through completion of the study.
  • Subjects must be willing and able to comply with the study restrictions and requirements.
  • Subjects or their or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.

Exclusion Criteria:

  • Subject's age < 6 years old or subject's weight < 21 kg.
  • Subjects with a known history, currently of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate: inflammatory bowel disease (if currently active) or have had prior resection of small intestine; Heart disease (e.g., myocardial infarction, heart failure, arrhythmias or poorly controlled hypertension) 90 days prior to Screening; Active bleeding disorder 90 days prior to Screening; Malignant disease within the last 2 years.
  • Patients with a hemoglobin level < 10 g/dL at Screening or a level that, in the opinion of the investigator, makes it unsafe for the subject to participate.
  • Subjects receiving any form of cysteamine medication through a gastric tube.
  • Subjects who are receiving maintenance dialysis or who have had a kidney transplant.
  • Subjects who are on an active kidney transplant list or who are planning to receive a kidney transplant within 3 months of Screening.
  • Subjects with known hypersensitivity to cysteamine or penicillamine.
  • Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or have a positive serum pregnancy screen.
  • Subjects who have a made a blood donation within 30 days of Screening.
  • Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01000961

Locations
United States, California
Stanford University Medical School
Stanford, California, United States, 94305
United States, Georgia
Emory Children's Center
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital)
Chicago, Illinois, United States, 60614
France
Hospices Civils de Lyon
Lyon, France
Villeneuve-Lapeyronie Hospital
Montpellier, France
Robert Debre Hospital
Paris, France
Necker Hospital
Paris, France
Netherlands
Radboud University Nijmegen Medical Center
Nijmegen, Netherlands
Sponsors and Collaborators
Raptor Pharmaceuticals Inc.
Investigators
Principal Investigator: Craig Langman, MD Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital)
  More Information

Publications:
Responsible Party: Raptor Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01000961     History of Changes
Other Study ID Numbers: RP103-03
Study First Received: October 22, 2009
Last Updated: September 17, 2012
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Raptor Pharmaceuticals Inc.:
cystinosis
cysteamine
inheritable disease
orphan disease
CTNS protein, human
metabolic disease
nephropathic cystinosis

Additional relevant MeSH terms:
Fanconi Syndrome
Cystinosis
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Lysosomal Storage Diseases
Cysteamine
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014