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

Cystinosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01197378
• Other study ID #: RP103-04
• Secondary ID: 2010-018365-34
• Status: Completed
• Phase: Phase 3
• Start date: August 27, 2010
• Est. completion date: June 26, 2017

Study information

• Verified date: June 2018
• Source: Horizon Pharma USA, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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®.

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 quarterly clinic visits for the duration of the study and home use of cysteamine bitartrate delayed-release capsules.

Initially, enrollment was open to those patients who had completed the previous Phase 3 Study (RP103-03, NCT01000961). Subsequently enrollment in Study RP103-04 was opened to additional participants, including children aged 1 to 6 years and renal transplant recipients, who had previously been on a stable dose of Cystagon® for at least 21 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 26, 2017
• Est. primary completion date: June 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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 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.

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 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.

Related Conditions & MeSH terms

• Cystinosis

Intervention

Drug:
• Cysteamine Bitartrate Delayed-release Capsules
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.

Locations

Country	Name	City	State
France	Hospices Civils de Lyon	Lyon
France	Hôpital Arnaud Villeneuve - CHU Montpellier	Montpellier
France	Hopital Necker	Paris
France	Robert Debre Hospital	Paris
Netherlands	Radboud University Nijmegen Medical Center	Nijmegen
United States	Emory Children's Center	Atlanta	Georgia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Texas Children's Hospital/Baylor University	Houston	Texas
United States	California Pacific Medical Center (CPMC) Research Institute	San Francisco	California
United States	Stanford University Medical School	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Horizon Pharma USA, Inc.

Countries where clinical trial is conducted

United States,  France,  Netherlands, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Trough Plasma Cysteamine Concentration	Plasma cysteamine concentration was determined using methods employing Hydrophilic Interaction Liquid Chromatography (HILC) high pressure liquid chromatography (HPLC) tandem mass spectrometry (HPLC-MS/MS).	Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
Secondary	White Blood Cell Cystine Concentration	White blood cell (WBC) cystine concentration was determined using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).	Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose

External Links

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