Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01744782
Recruitment Status : Completed
First Posted : December 7, 2012
Results First Posted : January 16, 2018
Last Update Posted : February 14, 2018
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Tracking Information
First Submitted Date  ICMJE December 5, 2012
First Posted Date  ICMJE December 7, 2012
Results First Submitted Date  ICMJE December 13, 2017
Results First Posted Date  ICMJE January 16, 2018
Last Update Posted Date February 14, 2018
Actual Study Start Date  ICMJE December 20, 2012
Actual Primary Completion Date December 13, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2017)
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit [ Time Frame: 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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2012)
  • White Blood Cell (WBC) Cystine Levels [ Time Frame: 12 Months ]
    Steady-state cysteamine-trough WBC cystine levels 30 minutes post RP103 dose at each study visit.
  • Long-Term Safety and Tolerability [ Time Frame: 12 months minimum ]
    The safety profile of RP103 will be investigated with the following assessments: physical exam, vital signs, ECG, clinical laboratory testing and adverse events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2017)
  • Number of Participants With Adverse Events [ Time Frame: Day 1 through study exit ]
    Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs). An AE/adverse experience was any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. For additional information regarding adverse events, please see the safety section of the record.
  • Maximum Observed Plasma Concentration (Cmax) of Cysteamine [ Time Frame: 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 ]
    Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. The maximum observed plasma concentration (Cmax) of cysteamine was determined directly from the data.
  • Time of the Maximum Observed Plasma Concentration (Tmax) of Cysteamine [ Time Frame: 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 ]
    Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. The time of the maximum observed plasma concentration (Tmax) of cysteamine was determined directly from the data.
  • Area Under the Plasma Concentration Versus Time Curve (AUC) of Cysteamine [ Time Frame: 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 ]
    Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. AUC values were estimated using non-compartmental analysis methods. AUClast was defined as the area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (720 minutes). AUCinf was defined as the area under the plasma concentration-versus-time curve from time 0 to infinity.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis
Official Title  ICMJE An Open-Label, Safety and Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naïve Patients With Cystinosis
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.
Detailed Description

The purpose of this study was to gather information about the safety and effectiveness (how well it works to treat cystinosis) of a new drug called RP103.

In cystinosis, the body builds up cystine. When taken regularly, the active ingredient of an older, already approved drug called Cystagon® (cysteamine bitartrate) reduces cystine in the body. RP103 has the same active ingredient as Cystagon® and is designed to reduce cystine in a similar way that Cystagon® does. RP103 is also different from Cystagon®: Instead of the cysteamine bitartrate being absorbed from the stomach, RP103 is designed to be absorbed from the small intestine. This may make the effects of the drug last longer, so that it can be taken twice a day instead of four times a day like Cystagon®.

To decide if RP103 is effective, the study used two types of blood tests. One test is pharmacodynamics (PD), which measures the amount of white blood cell (WBC) cystine after taking study drug. WBC cystine is a laboratory test used to find out if cysteamine bitartrate is reducing cystine levels in the body. The second test is pharmacokinetics (PK), which measures the amount of cysteamine in the blood after taking the drug.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cystinosis
Intervention  ICMJE Drug: RP103
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.
Other Name: Cysteamine Delayed-release Capsules
Study Arms  ICMJE Experimental: RP103
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.
Intervention: Drug: RP103
Publications * Schwartz GJ, Muñoz 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2017)
17
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2012)
10
Actual Study Completion Date  ICMJE December 13, 2016
Actual Primary Completion Date December 13, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01744782
Other Study ID Numbers  ICMJE RP103-08
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Horizon Pharma USA, Inc.
Study Sponsor  ICMJE Horizon Pharma USA, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Evelyn Olson, BS Horizon Pharma USA, Inc.
PRS Account Horizon Pharma USA, Inc.
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP