Phase 3 Study of Cysteamine Bitartrate Delayed-release (RP103) Compared to Cystagon® in Patients With Cystinosis

NCT ID: NCT01000961

Last Updated: 2024-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2011-08-31

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) 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®.

Detailed Description

This is a multi-center, open-label, randomized, cross-over study to determine whether steady-state, twice a day treatment with Cysteamine Bitartrate Delayed-release Capsules(RP103) results in comparable depletion of white blood cell (WBC) cystine levels compared to the existing four times a day cysteamine treatment. It will involve up to 20 clinic visits plus intermittent home use of the RP103. Most of these clinic visits occur in clusters of 3-4 consecutive days. Eligible patients will be offered enrollment into a long-term follow up study.

Study with completed results acquired from Horizon in 2024.

Conditions

Cystinosis

Keywords

cystinosis; cysteamine; inheritable disease; orphan disease; CTNS protein, human; metabolic disease; nephropathic cystinosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RP103 Q12H

Group Type: EXPERIMENTAL

Cysteamine Bitartrate Delayed-release Capsules (RP103)

Intervention Type: DRUG

Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:

Every 12H, supplied in 75 and 25mg capsules/Duration of Treatment: 3 weeks

Cystagon® Q6H

Group Type: ACTIVE_COMPARATOR

Cystagon® (Cysteamine Bitartrate)

Intervention Type: DRUG

Run-in Period (Weeks 1, 2, 3) and Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:

Every 6H, supplied in 150 and 50mg capsules/Duration of Treatment: 3 weeks each period used

Interventions

Cystagon® (Cysteamine Bitartrate)

Run-in Period (Weeks 1, 2, 3) and Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:

Every 6H, supplied in 150 and 50mg capsules/Duration of Treatment: 3 weeks each period used

Intervention Type: DRUG

Cysteamine Bitartrate Delayed-release Capsules (RP103)

Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1:

Every 12H, supplied in 75 and 25mg capsules/Duration of Treatment: 3 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female subjects must have nephropathic cystinosis.
• Subjects must be on a stable dose of Cystagon® sufficient to maintain their white blood cell (WBC) cystine level at ≤ 1.0 nmol/half-cystine/mg protein.
• Subjects must be able to swallow their typically administered Cystagon® capsule with the capsule intact.
• Within the last 6 months, no clinically significant change in liver function [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 or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.

Exclusion Criteria

• Subject's age < 6 years old or subject's weight < 21 kg.
• 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 who are receiving maintenance dialysis or who have had a kidney transplant.
• Subjects who are on an active kidney transplant list or who are planning to receive a kidney transplant within 3 months of Screening.
• 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 have a made a blood donation within 30 days of Screening.
• Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Stanford University Medical School

Stanford, California, United States

Emory Children's Center

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital)

Chicago, Illinois, United States

Hospices Civils de Lyon

Lyon, , France

Villeneuve-Lapeyronie Hospital

Montpellier, , France

Necker Hospital

Paris, , France

Robert Debre Hospital

Paris, , France

Radboud University Nijmegen Medical Center

Nijmegen, , Netherlands

Countries

United States; France; Netherlands

References

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. doi: 10.1016/j.jpeds.2006.01.050.

Reference Type: BACKGROUND

PMID: 16769383 (View on PubMed)

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. doi: 10.1111/j.1365-2125.2006.02734.x.

Reference Type: BACKGROUND

PMID: 17229040 (View on PubMed)

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. doi: 10.1007/s00467-005-2052-0. Epub 2005 Oct 27.

Reference Type: BACKGROUND

PMID: 16252107 (View on PubMed)

Related Links

http://www.procysbi.com

RP103 (marketed as PROCYSBI) is now approved by the US FDA for management of nephropathic cystinosis in patients 6 years and older

Other Identifiers

RP103-03

Identifier Type: -

Identifier Source: org_study_id