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

NCT01000961 | Completed Phase 3 Results

• 1 other identifier: RP103-03
• Study Type: interventional
• Target: 43
• Locations: 3 countries
• Sites: 8

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®.

Conditions

Cystinosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon®

  4 weeks after the last subject has completed the study

Secondary Outcomes (3)

• Comparison of Cysteamine PK Profiles, Steady State Cmax, Between RP103 and Cystagon®.

  4 weeks after the last subject has completed the study

• Comparison of Cysteamine PK Profiles, Steady State Tmax, Between RP103 and Cystagon®.

  4 weeks after the last subject has completed the study

• Comparison of Cysteamine PK Profiles, AUC(0-t), Between RP103 and Cystagon®.

  6 hours post dosing for Cystagon®; 12 hours post dosing for RP103.

Study Arms (2)

RP103 Q12H

EXPERIMENTAL

Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103)

Cystagon® Q6H

ACTIVE COMPARATOR

Drug: Cystagon® (Cysteamine Bitartrate)

Interventions

Cystagon® (Cysteamine Bitartrate) 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

Cystagon® Q6H

Cysteamine Bitartrate Delayed-release Capsules (RP103) 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

RP103 Q12H

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (8)

Stanford University Medical School

Stanford, California, 94305, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

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

Chicago, Illinois, 60614, United States

Location

Hospices Civils de Lyon

Lyon, France

Location

Villeneuve-Lapeyronie Hospital

Montpellier, France

Location

Necker Hospital

Paris, France

Location

Robert Debre Hospital

Paris, France

Location

Radboud University Nijmegen Medical Center

Nijmegen, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 16769383 BACKGROUND

• 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.

  PMID: 17229040 BACKGROUND

• 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.

  PMID: 16252107 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Cystinosis; Rare Diseases; Metabolic Diseases

Interventions

Cysteamine

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Results Point of Contact

• Title: Evelyn Olson, Director
• Organization: Horizon Pharma USA, Inc.

clinicaltrials@horizonpharma.com

224-383-3000

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2009
• First Posted: October 23, 2009
• Study Start: June 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: August 1, 2011
• Last Updated: December 19, 2024
• Results First Posted: November 19, 2014

Record last verified: 2024-11

Locations

US (3); NL (1); FR (4)