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

• ClinicalTrials.gov Identifier: NCT01000961
• Recruitment Status: Completed
• First Posted: October 23, 2009
• Results First Posted: November 19, 2014
• Last Update Posted: May 19, 2017
• Sponsor: Horizon Pharma USA, Inc.
• Information provided by (Responsible Party): Horizon Pharma USA, Inc.

Study Description

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®.

Condition or disease	Intervention/treatment	Phase
Cystinosis	Drug: Cystagon® (Cysteamine Bitartrate); Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103)	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Crossover Pharmacokinetic and Pharmacodynamic Study to Determine the Safety and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cystagon® in Patients With Nephropathic Cystinosis
• Study Start Date: June 2010
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: August 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: RP103 Q12H	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
Active Comparator: Cystagon® Q6H	Drug: 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

Outcome Measures

Primary Outcome Measures :

1. The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon® [ Time Frame: 4 weeks after the last subject has completed the study ]

Secondary Outcome Measures :

1. Comparison of Cysteamine PK Profiles, Steady State Cmax, Between RP103 and Cystagon®. [ Time Frame: 4 weeks after the last subject has completed the study ]
2. Comparison of Cysteamine PK Profiles, Steady State Tmax, Between RP103 and Cystagon®. [ Time Frame: 4 weeks after the last subject has completed the study ]
3. Comparison of Cysteamine PK Profiles, AUC(0-t), Between RP103 and Cystagon®. [ Time Frame: 6 hours post dosing for Cystagon®; 12 hours post dosing for RP103. ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

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 (formerly Children's Memorial Hospital)

Chicago, Illinois, United States, 60614

France

Hospices Civils de Lyon

Lyon, France

Villeneuve-Lapeyronie Hospital

Montpellier, France

Necker Hospital

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.

More Information

Additional Information:

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

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. doi: 10.1016/j.jpeds.2006.01.050.

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.

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.

• Responsible Party: Horizon Pharma USA, Inc.
• ClinicalTrials.gov Identifier: NCT01000961
• Other Study ID Numbers: RP103-03
• First Posted: October 23, 2009
• Results First Posted: November 19, 2014
• Last Update Posted: May 19, 2017
• Last Verified: April 2017

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