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Long-Term Safety Follow-up Study of Cysteamine Bitartrate Delayed-release Capsules (RP103)

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ClinicalTrials.gov Identifier: NCT01197378
Recruitment Status : Completed
First Posted : September 9, 2010
Results First Posted : July 24, 2018
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Brief Summary:
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 immediate release) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. Cysteamine bitartrate delayed-release capsules (RP103) is a formulation of cysteamine bitartrate that is being studied to see if it can be given less frequently, once every 12 hours, and have similar results to four times a day Cystagon®.

Condition or disease Intervention/treatment Phase
Cystinosis Drug: Cysteamine Bitartrate Delayed-release Capsules Phase 3

Detailed Description:

This is a long-term, open-label, study to determine the safety and tolerability of twice a day treatment with cysteamine bitartrate delayed-release capsules (RP103). It will involve 6-9 monthly clinic visits followed by quarterly clinic visits for the duration of the study and home use of cysteamine bitartrate delayed-release capsules.

Initially, enrollment was open to those patients who had completed the previous Phase 3 Study (RP103-03, NCT01000961). Subsequently enrollment in Study RP103-04 was opened to additional participants, including children aged 1 to 6 years and renal transplant recipients, who had previously been on a stable dose of Cystagon® for at least 21 days.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Long-Term, Open-Label, Safety and Efficacy Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis
Actual Study Start Date : August 27, 2010
Actual Primary Completion Date : June 26, 2017
Actual Study Completion Date : June 26, 2017


Arm Intervention/treatment
Experimental: Cysteamine Bitartrate
Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.
Drug: Cysteamine Bitartrate Delayed-release Capsules

Participants who entered the trial from the RP103-03 study continued treatment with cysteamine bitartrate every 12 hours at the last dose level prescribed during their participation in that study.

Participants not entering the trial from Study RP103-03 were started on twice a day administration of cysteamine bitartrate at a total daily RP103 dose of 70% of their pre-study total daily stable Cystagon® dose.

Other Names:
  • RP103
  • PROCYSBI®




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events [ Time Frame: From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days. ]

    Drug-related adverse events (AEs) are AEs the investigator assessed as having relation to drug of 'possibly', 'probably' or 'definitely'.

    The severity of AEs was categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 as follows:

    • Mild (Grade 1): experience is minor and does not cause significant discomfort to subject or change in activities of daily living (ADL); subject is aware of symptoms but symptoms are easily tolerated;
    • Moderate (Grade 2): experience is an inconvenience or concern to the subject and causes interference with ADL, but the subject is able to continue with ADL.
    • Severe (Grade 3): experience significantly interferes with ADL and the subject is incapacitated and/or unable to continue with ADL
    • Life-threatening (Grade 4): experience that, in the view of the Investigator, places the subject at immediate risk of death from the event as it occurred.


Secondary Outcome Measures :
  1. Trough Plasma Cysteamine Concentration [ Time Frame: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose ]
    Plasma cysteamine concentration was determined using methods employing Hydrophilic Interaction Liquid Chromatography (HILC) high pressure liquid chromatography (HPLC) tandem mass spectrometry (HPLC-MS/MS).

  2. White Blood Cell Cystine Concentration [ Time Frame: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose ]
    White blood cell (WBC) cystine concentration was determined using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects must have completed the last visit of Study RP103-03 and be willing to continue with RP103 treatment.

OR for patients who did not complete the RP103-03 study:

  • Male and female subjects must have cystinosis.
  • Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.
  • Within the last 6 months, no clinically significant change from normal in liver function tests (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin) and renal function (i.e., estimated glomerular filtration rate [eGFR]) at Screening as determined by the Investigator.
  • Subjects with an eGFR 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 parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.

Exclusion Criteria:

  • Patients enrolled in the previous Study RP103-03 who did not complete their last scheduled Study visit or who do not wish to continue on treatment with RP103.

AND for patients who did not complete the RP103-03 study:

  • Subjects less than 1 year old
  • 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, unstable 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 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, in the opinion of the Investigator, are not able or willing to comply with the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01197378


Locations
United States, California
California Pacific Medical Center (CPMC) Research Institute
San Francisco, California, United States, 94115
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
Chicago, Illinois, United States, 60614
United States, Texas
Texas Children's Hospital/Baylor University
Houston, Texas, United States, 77030
France
Hospices Civils de Lyon
Lyon, France
Hôpital Arnaud Villeneuve ‐ CHU Montpellier
Montpellier, France
Hopital Necker
Paris, France
Robert Debre Hospital
Paris, France
Netherlands
Radboud University Nijmegen Medical Center
Nijmegen, Netherlands
Sponsors and Collaborators
Horizon Pharma USA, Inc.
Investigators
Study Director: Evelyn Olson, BS Horizon Pharma USA, Inc.
  Study Documents (Full-Text)

Documents provided by Horizon Pharma USA, Inc.:
Study Protocol  [PDF] November 18, 2015
Statistical Analysis Plan  [PDF] August 7, 2017


Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT01197378     History of Changes
Other Study ID Numbers: RP103-04
2010-018365-34 ( EudraCT Number )
First Posted: September 9, 2010    Key Record Dates
Results First Posted: July 24, 2018
Last Update Posted: July 24, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Horizon Pharma USA, Inc.:
cystinosis
cysteamine
inheritable disease
orphan disease
CTNS protein, human
metabolic disease
nephropathic cystinosis

Additional relevant MeSH terms:
Cystinosis
Lysosomal Storage Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Cysteamine
Cystine Depleting Agents
Molecular Mechanisms of Pharmacological Action