Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis

NCT01744782 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RP103-08
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 2

Brief Summary

This was a long-term, open-label study of the safety, tolerability and effectiveness of RP103 in cystinosis patients who were naïve to any form of cysteamine treatment. Participants received RP103 treatment for at least 12 months. U.S. participants transitioned to the commercially approved drug PROCYSBI®. In Brazil, after at least 12 months of study participation and upon approval by the Brazilian regulatory authorities, participants were eligible to transition to a post-study drug supply program, and continue to receive the drug at no personal cost.

Conditions

Cystinosis

Keywords

Nephropathic Cystinosis; Cysteamine; Delayed-release Cysteamine; CTNS Protein, Human; Orphan Disease

Outcome Measures

Primary Outcomes (1)

• Mean White Blood Cell (WBC) Cystine Concentration at Each Visit

  Blood samples were taken 30 minutes after the morning RP103 dose at each study visit to determine White Blood Cell (WBC) cystine concentration. WBC cystine concentrations were determined using liquid chromatography.

  Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Month 6, Month 9, Month 12, Month 15, Month 18, Study Exit

Secondary Outcomes (4)

• Number of Participants With Adverse Events

  Day 1 through study exit

• Maximum Observed Plasma Concentration (Cmax) of Cysteamine

  30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later

• Time of the Maximum Observed Plasma Concentration (Tmax) of Cysteamine

  30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later

• Area Under the Plasma Concentration Versus Time Curve (AUC) of Cysteamine

  30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later

Study Arms (1)

RP103

EXPERIMENTAL

From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.

Drug: RP103

Interventions

RP103 DRUG

Cysteamine Bitartrate Delayed-release Capsules (RP103) were administered twice daily, orally or via gastrostomy tube (G-tube), after a 2-hour fast. The starting dose was one-quarter of the RP103 targeted maintenance dose based on age, weight, and body surface area. The recommended targeted maintenance dose for children up to 6 years old was 1 gram/m²/day, in 2 divided doses given Q12H. The dose was gradually escalated, in 10% steps, based on monitoring of WBC cystine levels 30 minutes after the morning RP103 dose collected every 2 weeks, until the participant's WBC cystine level was \<1 nmol ½ cystine/mg protein.

Also known as: Cysteamine Delayed-release Capsules

RP103

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female with a documented diagnosis of cystinosis
• No clinically significant change in liver function tests, i.e. 1.5 times upper limit of normal (ULN) for alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and/or 1.5 times ULN for total bilirubin, within 6 months prior to Screening
• No clinically significant change in renal function, i.e. estimated glomerular filtration rate (GFR) within 6 months prior to Screening
• Must have an estimated GFR \> 20 mL/minute/1.73m² (using the equation from Schwartz 2009 J Am Soc Nephrol 20:629-647)
• Female participants who are sexually active and of childbearing potential, i.e. not surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy) or at least 2 years naturally postmenopausal must agree to use an acceptable form of contraception from Screening through completion of the study. Acceptable forms of contraception for this study include hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to Screening, barrier (spermicidal condom or diaphragm with spermicide), IUD, or a partner who has been vasectomized for at least 6 months. Childbearing potential was defined as a female who had reached menarche.
• Participant or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study
• Had not taken any form of cysteamine bitartrate in the past

You may not qualify if:

• Current history of the following conditions or any other health issues that make it, in the opinion of the Investigator, unsafe for study participation:
• Inflammatory bowel disease if currently active, or prior resection of the small intestine
• Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias, or poorly controlled hypertension) within 90 days prior to Screening
• Active bleeding disorder within 90 days prior to Screening
• History of malignant disease within 2 years prior to Screening
• Hemoglobin level of \< 10 g/dL at Screening or, in the opinion of the investigator, a hemoglobin level that would make it unsafe for study participation
• Known hypersensitivity to penicillamine
• Female subjects who were nursing, planning a pregnancy, or were known or suspected to be pregnant
• Participants who, in the opinion of the investigator, were not able or willing to comply with study requirements
• Had received a kidney transplant or was currently on dialysis
• Was 6 years of age or older at the time of the Screening visit

Sponsors & Collaborators

• Amgen: lead

Study Sites (2)

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, São Paulo, Brazil

Location

Related Publications (1)

• Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21.

  PMID: 19158356 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Cystinosis; Rare Diseases

Condition Hierarchy (Ancestors)

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

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

Study Record Dates

• First Submitted: December 5, 2012
• First Posted: December 7, 2012
• Study Start: December 20, 2012
• Primary Completion: December 13, 2016
• Study Completion: December 13, 2016
• Last Updated: December 27, 2024
• Results First Posted: January 16, 2018

Record last verified: 2024-12

Locations

US (1); BR (1)