Open-Label Safety & Superior Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cystinosis

This study is currently recruiting participants.
Verified December 2013 by Raptor Pharmaceuticals Inc.
Information provided by (Responsible Party):
Raptor Pharmaceuticals Inc. Identifier:
First received: November 16, 2012
Last updated: December 10, 2013
Last verified: December 2013

The purpose of this study is to gather information about the effectiveness (how well it works to treat cystinosis) and safety of a new form of cysteamine bitartrate called RP103, compared to the already-approved drug cystinosis patients are taking called Cystagon®.

In cystinosis, the body builds up cystine. When taken regularly, the active ingredient of Cystagon® (cysteamine bitartrate) reduces cystine in the body. RP103 has the same active ingredient as Cystagon® and is designed to reduce cystine in a similar way that Cystagon® does. To decide if RP103 is better than Cystagon®, the study will look at two types of blood tests. One test is pharmacodynamics (PD), which measures the amount of white blood cell (WBC) cystine after taking study drug. WBC cystine is a laboratory test used to find out if cysteamine bitartrate is reducing cystine levels in the body. The second test is pharmacokinetics (PK), which measures the amount of cysteamine in the blood after taking the drug.

RP103 is different from Cystagon®: Instead of the cysteamine bitartrate being absorbed from the stomach, RP103 is designed to be absorbed from the small intestine. This may make the effects of the drug last longer, so that it can be taken twice a day instead of four times a day like Cystagon®.

Some cystinosis patients have bad breath (halitosis) when they take Cystagon®. Study participants who experience bad breath with Cystagon® will be asked if they would like to participate in an optional "halitosis substudy" to investigate this issue by collecting some extra PK blood samples.

Condition Intervention Phase
Drug: RP103 Q12H
Drug: Cystagon Q6H
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Long-Term, Open-Label, Safety and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis

Resource links provided by NLM:

Further study details as provided by Raptor Pharmaceuticals Inc.:

Primary Outcome Measures:
  • White Blood Cell (WBC) Cystine Levels [ Time Frame: 7 Months ] [ Designated as safety issue: Yes ]
    Superior effectiveness of RP103 vs. Cystagon® will be evaluated comparing WBC cystine levels during two 3-month treatment periods (Cystagon® and RP103). An interim analysis will be performed after 20 subjects complete the two treatment periods; A final analysis will be performed after all 60 subjects have completed.

  • Long-Term Safety and Tolerability [ Time Frame: 7 Months minimum; 24 months maximum ] [ Designated as safety issue: Yes ]
    The safety profile of RP103 will be investigated with the following assessments: physical examination, vital signs, ECG, clinical laboratory testing and adverse events.

Secondary Outcome Measures:
  • Quality of Life - General [ Time Frame: 7 months minimum; 24 months maximum ] [ Designated as safety issue: No ]
    Long-term general quality of life will be assessed using instruments appropriate to the subjects' age and region (US or Europe).

  • Quality of Life - Fatigue/Sleep [ Time Frame: 7 months; 24 months maximum ] [ Designated as safety issue: No ]
    Long-term quality of life, specifically fatigue/sleep, will be assessed using instruments appropriate to the subjects' age and region (US or Europe).

Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cystagon Q6H
From Screening and during Months 1, 2, 3: all subjects will take Cystagon (cysteamine bitartrate) every 6 hours, supplied in 150 and 50mg capsules.
Drug: Cystagon Q6H
Other Name: Cystagon (cysteamine bitartrate)
Experimental: RP103 Q12H
From Months 3.5, 4, 5, 6, 7 and the remainder of participation: all subjects will take RP103 (cysteamine bitartrate delayed-release capsules) every 12 hours, supplied in 75 and 25mg capsules.
Drug: RP103 Q12H
Other Name: RP103 (cysteamine bitartrate delayed-release capsules)


Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Male or female with a documented diagnosis of cystinosis
  • On a stable dose of Cystagon at least 21 days prior to Screening
  • WBC cystine level > 1 nmol 1/2 cystine/mg of protein, on average over at least 2 measurements collected during the 2 years prior to Screening
  • No clinically significant change in liver function tests, i.e. 1.5 times ULN for ALT and 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 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 subjects 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.
  • Subject or their parent or guardian must provide written informed consent, assent (where applicable), prior to participation in the study


  • Younger than 12 years of age
  • 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 < 9 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 cysteamine and penicillamine
  • Female subjects who are nursing, planning a pregnancy, or are known or suspected to be pregnant
  • Subjects who, in the opinion of the investigator, are not able or willing to comply with study requirements
  Contacts and Locations
Please refer to this study by its identifier: NCT01733316

Contact: Mary Jo Bagger, Clinical Operations, Raptor Pharmaceuticals Inc. 1-415-408-6210
Contact: Margo Kamel, Clinical Research Coordinator, Emory Children's Center

United States, California
California Pacific Medical Center (CPMC) Research Institute Active, not recruiting
San Francisco, California, United States, 94115
Stanford University Medical School Active, not recruiting
Stanford, California, United States, 94305
United States, Georgia
Emory Children's Center Active, not recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Active, not recruiting
Chicago, Illinois, United States, 60614
United States, Texas
Baylor College of Medicine / Texas Childrens Hospital Active, not recruiting
Houston, Texas, United States, 77030
University Hospital of Leuven Not yet recruiting
Leuven, Belgium
Contact: Elena Levtchenko, MD, PhD    +32 16 343827   
Contact: Martine Besouw, PhD    +32 89 327649   
Principal Investigator: Elena Levtchenko, MD, PhD         
Hospices Civils de Lyon Recruiting
Lyon, France
Contact: Aurelia Bertholet-Thomas, MD    +33 (4) 72 11 03 51   
Contact: Segolene Gaillard    +33 (4) 72 35 75 51   
Principal Investigator: Pierre Cochat, MD         
Hôpital Necker-Enfants Malades Recruiting
Paris, France
Contact: Agnés Mogenet, MD    +33 (1) 44 49 47 44   
Contact: , MD         
Principal Investigator: Rémi Salomon, MD         
Hôpital Robert Debré Recruiting
Paris, France
Contact: Florence Emmanuel    +33 (1) 40 03 36 41   
Principal Investigator: Georges Deschênes, MD, PhD         
Ospedale Pediatrico Bambino Gesù Recruiting
Rome, Italy
Contact: Marcella Greco, MD   
Contact: Susanna Livadiotti    +39 (06) 68 59 30 81   
Principal Investigator: Marcella Greco, MD         
Radboud University Nijmegen Medical Center Recruiting
Nijmegen, Netherlands
Contact: Mariette Las    +31 (24) 36 68 957   
Principal Investigator: Marlies Cornelissen, MD, PhD         
United Kingdom
Queen Elizabeth Hospital Birmingham Not yet recruiting
Birmingham, United Kingdom
Contact: Graham Lipkin, MD, FRCP   
Principal Investigator: Graham Lipkin, MD, FRCP         
Great Ormond Street Not yet recruiting
London, United Kingdom
Contact: William van't Hoff, MD, FRCPCH   
Principal Investigator: William van't Hoff, MD, FRCPCH         
Sponsors and Collaborators
Raptor Pharmaceuticals Inc.
Principal Investigator: Laurence A Greenbaum, MD, PhD (US) Emory University
Principal Investigator: Georges Deschênes, MD, PhD (EU) Hôpital Robert Debré
  More Information

Responsible Party: Raptor Pharmaceuticals Inc. Identifier: NCT01733316     History of Changes
Other Study ID Numbers: RP103-07, 2012-002773-64
Study First Received: November 16, 2012
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Raptor Pharmaceuticals Inc.:
Nephropathic Cystinosis
Delayed-Release Cysteamine
Orphan Disease
CTNS Protein, Human

Additional relevant MeSH terms:
Nephrotic Syndrome
Lysosomal Storage Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions processed this record on April 16, 2014