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

NCT01197378 | Completed Phase 3 Results

• 2 other identifiers: RP103-042010-018365-34
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 10

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 immediate release) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. Cysteamine bitartrate delayed-release capsules (RP103) is a formulation of cysteamine bitartrate that is being studied to see if it can 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)

• Number of Participants With Treatment-emergent Adverse Events

  Drug-related adverse events (AEs) are AEs the investigator assessed as having relation to drug of 'possibly', 'probably' or 'definitely'. The severity of AEs was categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 as follows: * Mild (Grade 1): experience is minor and does not cause significant discomfort to subject or change in activities of daily living (ADL); subject is aware of symptoms but symptoms are easily tolerated; * Moderate (Grade 2): experience is an inconvenience or concern to the subject and causes interference with ADL, but the subject is able to continue with ADL. * Severe (Grade 3): experience significantly interferes with ADL and the subject is incapacitated and/or unable to continue with ADL * Life-threatening (Grade 4): experience that, in the view of the Investigator, places the subject at immediate risk of death from the event as it occurred.

  From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days.

Secondary Outcomes (2)

• Trough Plasma Cysteamine Concentration

  Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose

• White Blood Cell Cystine Concentration

  Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose

Study Arms (1)

Cysteamine Bitartrate

EXPERIMENTAL

Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.

Drug: Cysteamine Bitartrate Delayed-release Capsules

Interventions

Cysteamine Bitartrate Delayed-release Capsules DRUG

Participants who entered the trial from the RP103-03 study continued treatment with cysteamine bitartrate every 12 hours at the last dose level prescribed during their participation in that study. Participants not entering the trial from Study RP103-03 were started on twice a day administration of cysteamine bitartrate at a total daily RP103 dose of 70% of their pre-study total daily stable Cystagon® dose.

Also known as: RP103, PROCYSBI®

Cysteamine Bitartrate

Eligibility Criteria

• Age: 1 Year+
• 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 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 cystinosis.
• Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.
• Within the last 6 months, no clinically significant change from normal in liver function tests (i.e., alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], total bilirubin) and renal function (i.e., estimated glomerular filtration rate \[eGFR\]) at Screening as determined by the Investigator.
• Subjects with an eGFR 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.

You may not qualify if:

• 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 less than 1 year old
• 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, unstable 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 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (10)

California Pacific Medical Center (CPMC) Research Institute

San Francisco, California, 94115, United States

Location

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

Chicago, Illinois, 60614, United States

Location

Texas Children's Hospital/Baylor University

Houston, Texas, 77030, United States

Location

Hospices Civils de Lyon

Lyon, France

Location

Hôpital Arnaud Villeneuve - CHU Montpellier

Montpellier, France

Location

Hopital Necker

Paris, France

Location

Robert Debre Hospital

Paris, France

Location

Radboud University Nijmegen Medical Center

Nijmegen, Netherlands

Location

Related Publications (4)

• 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

• Langman CB, Greenbaum LA, Grimm P, Sarwal M, Niaudet P, Deschenes G, Cornelissen EA, Morin D, Cochat P, Elenberg E, Hanna C, Gaillard S, Bagger MJ, Rioux P. Quality of life is improved and kidney function preserved in patients with nephropathic cystinosis treated for 2 years with delayed-release cysteamine bitartrate. J Pediatr. 2014 Sep;165(3):528-33.e1. doi: 10.1016/j.jpeds.2014.05.013. Epub 2014 Jun 16.

  PMID: 24948347 DERIVED

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
• 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 9, 2010
• Study Start: August 27, 2010
• Primary Completion: June 26, 2017
• Study Completion: June 26, 2017
• Last Updated: December 27, 2024
• Results First Posted: July 24, 2018

Record last verified: 2024-12

Locations

NL (1); FR (4); US (5)