Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics (PK/PD) of RP103 Compared to Cystagon® in Patients With Cystinosis

Condition(s) targeted: Cystinosis

Intervention: Cystagon® (Cysteamine Bitartrate) Capsules: 150 mg/50 mg (Drug); RP103 (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Raptor Therapeutics, Inc.

Official(s) and/or principal investigator(s):
Bruce Barshop, MD, PhD, Principal Investigator, Affiliation: UCSD

Overall contact:
Patrice P Rioux, MD, PhD, Phone: 1-888-270-3828, Email: ClinicalTrials@RaptorPharma.com

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.

Official title: 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

Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics/Dynamics Study

Primary outcome: To assess the safety and tolerability of RP103 compared to Cystagon®

Secondary outcome:

Pharmacodynamic profile of white cell cystine depletion of RP103 compared to Cystagon®

Comparison of plasma PK parameters of cysteamine between RP103 and Cystagon®

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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

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.

Patrice P Rioux, MD, PhD, Phone: 1-888-270-3828, Email: ClinicalTrials@RaptorPharma.com

University of California San Diego Medical Center, San Diego, California 92103, United States; Recruiting
Bruce Barshop, MD
Betty Cabrera, BS, MPH, Phone: 619-471-9554, Email: blcabrera@ucsd.edu
Bruce Barshop, MD, PhD, Principal Investigator

Click here for more information about Raptor's cysteamine program

Click here for more information about UCSD's cystinosis program

Related publications:

Dohil R, Fidler M, Barshop BA, Gangoiti J, Deutsch R, Martin M, Schneider JA. Understanding intestinal cysteamine bitartrate absorption. J Pediatr. 2006 Jun;148(6):764-9.

Fidler MC, Barshop BA, Gangoiti JA, Deutsch R, Martin M, Schneider JA, Dohil R. Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. Br J Clin Pharmacol. 2007 Jan;63(1):36-40.

Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA, Blom HJ. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006 Jan;21(1):110-3. Epub 2005 Oct 27.

Starting date: May 2009
Ending date: October 2009
Last updated: September 23, 2009