Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of 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:
NCT00872729
First received: March 27, 2009
Last updated: October 24, 2014
Last verified: October 2014
  Purpose

Cystinosis is an inheritable 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.


Condition Intervention Phase
Cystinosis
Drug: Cystagon®
Drug: RP103
Phase 1
Phase 2

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 Pilot Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cysteamine Bitartrate (Cystagon®) in Patients With Nephropathic Cystinosis

Resource links provided by NLM:


Further study details as provided by Raptor Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Plasma Pharmacokinetic Parameter: Cmax of Cysteamine [ Time Frame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing ] [ Designated as safety issue: No ]
  • Plasma Pharmacokinetic Parameter: Tmax of Cysteamine [ Time Frame: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing ] [ Designated as safety issue: No ]
  • Plasma Pharmacokinetic Parameter: AUC(0-t) of Cysteamine [ Time Frame: 12 hours post RP103 dosing and 6 hours post 1st Cystagon® dosing ] [ Designated as safety issue: No ]
    t = 6 for Cystagon and t = 12 for RP103. Cystagon is dosed every 6 hours and there is no measurement after 6 hours and up to 12 hours.

  • Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline [ Time Frame: up to 12 hours post Cystagon® dosing and RP103 dosing ] [ Designated as safety issue: No ]

    The pharmacodynamic (PD) parameter measures the changes of WBC cystine level from the baseline.

    Cystine is a disulfide amino acid formed through oxidation of two molecules of cysteine; hence, cystine's concentration is commonly given in half-cystine equivalents to avoid confusion.

    The level of cystine in WBC/leukocytes is expressed in units of nmol half-cystine/mg protein (nmol ½ cystine/mg protein). Half-cystine is quantified by a reduction of cystine followed by an assay for cysteine, which is then normalized by the total cellular protein content within the sample using methods of such as Lowry assay, bicinchoninic acid assay, or Bradford.



Enrollment: 9
Study Start Date: May 2009
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cystagon®
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg
Drug: Cystagon®

Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.

Duration of Treatment and Dose: Reference Period up to four doses Q6H.

Experimental: RP103
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg
Drug: RP103

Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.

Duration of treatment and Dose: Single dose of Test Product at dose equivalent to Reference Product.


Detailed Description:

This is a single-dose, open-labeled, non-randomized, two-period study of Cysteamine Bitartrate Delayed-release Capsules (RP103) and Cystagon® in up to 10 patients (male or female) with nephropathic cystinosis under fasting conditions. It will involve a 4 night check-in to a clinical research center.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects must have nephropathic cystinosis.
  • Children less than 22.5 kg will only be included in the study if the investigator feels they can safely participate in the study including the required blood draw volume for the safety and PK/PD assessments.
  • Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.
  • Subjects must be able to swallow a 150 mg Cystagon® capsule with the capsule intact.
  • Within the last 2 months, no clinically significant change in liver function [i.e., ALT, AST, alkaline phosphatase, bilirubin (total and direct)] and renal function [i.e., serum creatinine, albumin, total protein] at Screening as determined by the Investigator.
  • 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 or their authorized caregiver must provide written informed consent and assent (where applicable) prior to participation in the study.
  • If in the opinion of the investigator, patients can safely provide the study required blood draw volume.
  • Subjects must be willing and able to comply with the study restrictions and requirements.

Exclusion Criteria:

  • If, in the opinion of the investigator, the planned study dose would exceed the patient's tolerability of cysteamine based on their prior Cystagon® steady state drug requirements.
  • Evidence of or verbal attestation of Helicobacter pylori infection, presently, or within the last 90 days prior to Screening.
  • Subjects with a known history, currently or within the past 90 days prior to Screening, of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate, or whose concomitant medical problems preclude them from committing to the study schedule including the following: Crohn's disease, inflammatory bowel disease (if currently active) or have had prior resection of small intestine; • History of heart disease, e.g., myocardial infarction, heart failure, arrhythmias; Any bleeding disorder; Malignant disease; Severe liver disease as defined as ALT or AST > 2 times the upper limit of normal.
  • Subjects who have had a kidney transplant.
  • Subjects who are planning or are a registered candidate for a kidney transplant within 3 months of the Screening or have a serum creatinine > 2.4.
  • Subjects with known hypersensitivity to cysteamine.
  • If female (of child-bearing potential), are nursing, planning a pregnancy, known or suspected to be pregnant, or have a positive urine pregnancy screen.
  • Patients with a hemoglobin level < 10.5.
  • Subjects who have a made a blood donation within 60 days prior to study initiation.
  • 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: NCT00872729

Locations
United States, California
University of California San Diego Medical Center
San Diego, California, United States, 92103
Sponsors and Collaborators
Raptor Pharmaceuticals Inc.
Investigators
Principal Investigator: Bruce Barshop, MD, PhD UCSD
  More Information

Additional Information:
Publications:
Responsible Party: Raptor Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00872729     History of Changes
Other Study ID Numbers: RP103-01
Study First Received: March 27, 2009
Results First Received: October 5, 2012
Last Updated: October 24, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 29, 2014