We updated the design of this site on December 18, 2017. Learn more.
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.

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.

Condition or disease Intervention/treatment Phase
Cystinosis Drug: RP103 Phase 3

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 : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Safety and Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naïve Patients With Cystinosis
Actual Study Start Date : December 20, 2012
Primary Completion Date : December 13, 2016
Study Completion Date : December 13, 2016


Arm Intervention/treatment
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.
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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01744782


Locations
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo
Sao Paulo, SP, Brazil
Sponsors and Collaborators
Horizon Pharma USA, Inc.
Investigators
Study Director: Evelyn Olson, BS Horizon Pharma USA, Inc.

Additional Information:
Publications:
Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT01744782     History of Changes
Other Study ID Numbers: RP103-08
First Posted: December 7, 2012    Key Record Dates
Results First Posted: January 16, 2018
Last Update Posted: February 14, 2018
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Horizon Pharma USA, Inc.:
Nephropathic Cystinosis
Cysteamine
Delayed-release Cysteamine
CTNS Protein, Human
Orphan Disease

Additional relevant MeSH terms:
Cystinosis
Lysosomal Storage Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Cysteamine
Cystine Depleting Agents
Molecular Mechanisms of Pharmacological Action