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Trial record 9 of 33 for:    CYSTEAMINE

Open-Label, Safety and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-Release Capsules (RP103) in 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: NCT01733316
Recruitment Status : Completed
First Posted : November 27, 2012
Results First Posted : May 24, 2017
Last Update Posted : August 13, 2018
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Tracking Information
First Submitted Date  ICMJE November 16, 2012
First Posted Date  ICMJE November 27, 2012
Results First Submitted Date  ICMJE April 10, 2017
Results First Posted Date  ICMJE May 24, 2017
Last Update Posted Date August 13, 2018
Actual Study Start Date  ICMJE January 31, 2013
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values [ Time Frame: While taking Cystagon® (Months 1, 2, 3): within 15 minutes pre-morning (AM) and pre-non AM dose. During 3 months of RP103 (Months 5, 6, 7): 30 minutes post-AM and post-evening (PM) dose. ]
The primary analysis of WBC cystine was performed using the natural log transformed WBC cystine level; the log transformation is a normalizing transformation. For each participant, the difference between the morning and corresponding non-morning log WBC cystine value (non-morning minus morning) at each monthly visit during the Cystagon® phase (Months 1, 2, and 3) was computed and these differences were averaged. The average difference between morning and non-morning log WBC cystine value was similarly computed for each participant during the RP103 phase (Months 5, 6, and 7). The primary analysis compared within-subject pairs (Cystagon® phase paired with RP103 phase) of non-morning minus morning average differences of log WBC cystine level.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2012)
  • White Blood Cell (WBC) Cystine Levels [ Time Frame: 7 Months ]
    Superior effectiveness of RP103 vs. Cystagon® will be evaluated comparing WBC cystine levels during two 3-month treatment periods (Cystagon® and RP103). An interim analysis will be performed after 20 subjects complete the two treatment periods; A final analysis will be performed after all 60 subjects have completed.
  • Long-Term Safety and Tolerability [ Time Frame: 7 Months minimum; 24 months maximum ]
    The safety profile of RP103 will be investigated with the following assessments: physical examination, vital signs, ECG, clinical laboratory testing and adverse events.
Change History Complete list of historical versions of study NCT01733316 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs [ Time Frame: From first dose of study drug to 7 days after last dose. Median duration of exposure was 91 days (range 82-108) for Cystagon® phase, 119 days (range 98-137) for the RP103 phase, and 861 days (range 30 - 1350) during the long-term RP-103 phase. ]
    AE: any untoward medical occurrence that does not necessarily have a causal relationship with study drug. SAE: any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is medically significant, and though not included in the above list, is an important medical event, according to the Investigator. Treatment-emergent adverse events (TEAEs) occurred after first dose of study drug. Clinically significant abnormalities in laboratory values (hematology, blood chemistry, urinalysis), electrocardiograms (ECGs), vital signs, and physical examinations were to be reported as adverse events and so are included in this summary of TEAEs
  • Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine [ Time Frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose ]
    Participants who reported halitosis ("bad breath") as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of dimethylsulfide (DMS) in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state pharmacokinetic (PK) samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
  • Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine [ Time Frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose ]
    Participants who reported halitosis ("bad breath") as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
  • Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine [ Time Frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose ]
    Participants who reported halitosis ("bad breath") as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
  • Halitosis Substudy: Expired Air DMS Concentrations [ Time Frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose 30 min post-dose, 2, 3, 4 and 6 hours post-dose. While taking RP103 (Month 4, 5, or 7): Within 15 min. prior to morning dose. 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose ]
    Participants who reported halitosis ("bad breath") as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2012)
  • Quality of Life - General [ Time Frame: 7 months minimum; 24 months maximum ]
    Long-term general quality of life will be assessed using instruments appropriate to the subjects' age and region (US or Europe).
  • Quality of Life - Fatigue/Sleep [ Time Frame: 7 months; 24 months maximum ]
    Long-term quality of life, specifically fatigue/sleep, will be assessed using instruments appropriate to the subjects' age and region (US or Europe).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-Label, Safety and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-Release Capsules (RP103) in Cystinosis
Official Title  ICMJE A Long-Term, Open-Label, Safety, Tolerability and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis
Brief Summary

The purpose of this study is to gather information about the effectiveness (how well it works to treat cystinosis) and safety of a new form of cysteamine bitartrate called RP103, compared to the already-approved drug cystinosis patients are taking called Cystagon®.

In cystinosis, the body builds up cystine. When taken regularly, the active ingredient of 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. To decide if RP103 is better than Cystagon®, the study will look at 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.

RP103 is 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®.

Some cystinosis patients have bad breath (halitosis) when they take Cystagon®. Study participants who experience bad breath with Cystagon® will be asked if they would like to participate in an optional "halitosis substudy" to investigate this issue by collecting some extra PK blood samples.

Detailed Description Not Provided
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
    Other Names:
    • cysteamine bitartrate delayed-release capsules
    • PROCYSBI®
  • Drug: Cystagon®
    Other Name: cysteamine bitartrate
Study Arms  ICMJE Experimental: All Participants

Cystagon® Phase: From Screening and during Months 1, 2, 3 participants receive their usual dose of Cystagon® every 6 hours (Q6H).

RP103 Phase: During Months 3.5, 4, 5, 6, 7 participants receive RP103 every 12 hours (Q12H).

Long Term Phase: On or after Month 7, for the remainder of study participants receive RP103 Q12H.

Interventions:
  • Drug: RP103
  • Drug: Cystagon®
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: May 19, 2017)
41
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2012)
60
Actual Study Completion Date  ICMJE July 10, 2017
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  • Male or female with a documented diagnosis of cystinosis
  • On a stable dose of Cystagon® at least 21 days prior to Screening
  • WBC cystine level > 1 nmol 1/2 cystine/mg of protein, on average over at least 2 measurements collected during the 2 years prior to Screening
  • No clinically significant change in liver function tests, i.e. 1.5 times upper limit of normal (ULN) for alanine aminotransferase and aspartate aminotransferase, 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/1.73m^2 (using the equation from Schwartz 2009 J Am Soc Nephrol 20:629-647)
  • Female subjects 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), intrauterine device, or a partner who has been vasectomized for at least 6 months.
  • Subject or their parent or guardian must provide written informed consent, assent (where applicable), prior to participation in the study

EXCLUSION CRITERIA:

  • Younger than 12 years of age
  • 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 < 9 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 cysteamine and penicillamine
  • Female subjects who are nursing, planning a pregnancy, or are known or suspected to be pregnant
  • Subjects who, in the opinion of the investigator, are not able or willing to comply with study requirements.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01733316
Other Study ID Numbers  ICMJE RP103-07
2012-002773-64 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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 July 2018

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