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

Condition(s) targeted: Cystinosis

Intervention: Cysteamine Bitartrate Delayed-release Capsules (RP103) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Raptor Pharmaceutical Corp.

Official(s) and/or principal investigator(s):
Craig Langman, MD, Principal Investigator, Affiliation: Children's Memorial Hospital

Overall contact:
Mary Jo Bagger, Clinical Operations, Raptor Pharmaceutical Corp., Phone: 1-888-270-3828, Email: clinicaltrials@raptorpharma.com

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®.

Official title: A Long-Term, Open-Label, Safety and Efficacy Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Nephropathic Cystinosis

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Safety and tolerability of long-term repeat dosing of RP103 in patients with nephropathic cystinosis.

Secondary outcome:

Steady-state pharmacokinetics (PK) and pharmacodynamics (PD) of RP103.

Long term quality of life using either PedsQL™ or SF-36® instruments.

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 up to 6 quarterly clinic visits for the duration of the study and home use of RP103. Enrollment will be offered first to those patients who have completed the previous Phase 3 Study (RP103-03)and won't be offered to others until data analysis of the RP103-03 subjects has been completed.

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

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 nephropathic cystinosis.

- Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.

- Subjects must be able to swallow their typically administered Cystagon® capsule with

the capsule intact.

- Within the last 6 months, no clinically significant change from normal in liver

function tests[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 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 who cannot take intact Cystagon® capsules orally.

- 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 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.

Mary Jo Bagger, Clinical Operations, Raptor Pharmaceutical Corp., Phone: 1-888-270-3828, Email: clinicaltrials@raptorpharma.com

Villeneuve-Lapeyronie Hospital, Montpellier, France; Recruiting
Hugues Chevassus, Phone: +33 (4) 67 33 23 25, Email: h-chevassus@chu-montpellier.fr
Denis Morin, MD, PhD, Principal Investigator

Robert Debre Hospital, Paris, France; Recruiting
Florence Emmanuel, Phone: +33 (1) 40 03 36 41, Email: florence.emmanuel@rdb.aphp.fr
Georges Deschenes, MD, PhD, Principal Investigator

Hopital Necker, Paris, France; Recruiting
Patrick Niaudet, MD, Phone: +33 (1) 44 49 44 62, Email: pniaudet@gmail.com
Patrick Niaudet, MD, Principal Investigator

Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; Recruiting
Jos Gilissen, Phone: +31 (24) 366 8956, Email: j.gilissen@cukz.umcn.nl
Marlies Cornelissen, MD, PhD, Principal Investigator

Stanford University Medical School, Stanford, California 94305, United States; Recruiting
Xiaoxiao Gao, Email: xiaoxiao@stanford.edu
Minnie Sarwal, MD, PhD, Principal Investigator

Emory Children's Center, Atlanta, Georgia 30322, United States; Recruiting
Margret Kamel, MSPH, Email: cystinosistrial@oz.ped.Emory.edu
Laurence A Greenbaum, MD, PhD, Principal Investigator

Children's Memorial Hospital, Chicago, Illinois 60614, United States; Recruiting
Heather Price, Email: hprice@childrensmemorial.org
Craig Langman, MD, Principal Investigator

Texas Children's Hospital/Baylor University, Houston, Texas 77030, United States; Recruiting
Heidy Godoy, Phone: 832-824-1580, Email: hjgodoy@texaschildrens.org
Ewa Elenberg, MD, Principal Investigator

Click here for more information about Raptor's cysteamine 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: August 2010
Last updated: June 10, 2011