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A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease

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. Identifier: NCT02473445
Recruitment Status : Terminated (Sponsor decision to end development of RP103 for mitochondrial disease due to lack of efficacy demonstrated in base study RP103-MITO-001.)
First Posted : June 16, 2015
Results First Posted : May 11, 2018
Last Update Posted : May 11, 2018
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Tracking Information
First Submitted Date  ICMJE June 10, 2015
First Posted Date  ICMJE June 16, 2015
Results First Submitted Date  ICMJE March 6, 2018
Results First Posted Date  ICMJE May 11, 2018
Last Update Posted Date May 11, 2018
Actual Study Start Date  ICMJE May 19, 2015
Actual Primary Completion Date March 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2018)
Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Score [ Time Frame: Baseline, every 3 months and Study Exit (up to 24 Months) ]
The NPMDS evaluates the progression of mitochondrial disease in pediatric patients in 4 domains: I - Current Function (vision, hearing, communication, feeding, and mobility) with scores ranging from 0 to 21; II - System Specific Involvement (seizures, encephalopathy, bleeding diathesis or coagulation defects, gastrointestinal, endocrine, respiratory, cardiovascular, renal, liver, and blood) with scores ranging from 0 to 30. III - Current Clinical Assessment (growth and development over past 6 months, vision, strabismus and eye movement, myopathy, ataxia, pyramidal, extrapyramidal, and neuropathy) with scores ranging from 0 to 28; IV - Quality of Life with scores ranging from 0 to 25. For sections I-III, higher scores reflect more severe disease. For Section IV, a higher score reflects a lower quality of life.
Original Primary Outcome Measures  ICMJE
 (submitted: June 11, 2015)
Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Score [ Time Frame: Time Frame: Baseline vs. Month 24 ]
Quality of Life
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2018)
  • Change Over Time in Two of the Most Pre-eminent Symptoms [ Time Frame: Baseline, every 3 months and Study Exit (up to 24 Months) ]
    The two pre-eminent symptoms previously identified in study RP103-MITO-001 were to be continued to be assessed during the extension study. Symptoms included myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision.
  • Change Over Time in Pharmacodynamic Biomarkers [ Time Frame: Baseline, every 3 months and Study Exit (up to 24 Months) ]
    Change from baseline in glutathione, glutathione disulfide, and lactate analyses were not performed as the study was prematurely terminated.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2015)
Change in pre-eminent symptom scales (choice of 6-minute walk; Jama dynamometer; Barry-Albright Dystonia Scale; Friedreich Ataxia Rating Scale;Gross Motor Function Measure; Modified Lansky Play Performance Scale; Vision/Eye Examination) [ Time Frame: Time Frame: Baseline vs. Month 24 ]
Quality of life
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: June 11, 2015)
Change over time in Pharmacodynamic Biomarkers [ Time Frame: Time Frame: Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24 ]
glutathione, glutathione disulfide, lactate
Descriptive Information
Brief Title  ICMJE A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
Official Title  ICMJE A Long-Term Open-Label Extension Study of RP103-MITO-001 to Assess the Safety, Tolerability and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease
Brief Summary A long-term extension study to assess the safety, tolerability and efficacy of cysteamine bitartrate delayed-release capsules (RP103) in children with inherited mitochondrial diseases who previously enrolled into study RP103-MITO-001 (NCT02023866).
Detailed Description

Patients with inherited mitochondrial diseases associated with nuclear or mitochondrial deoxyribonucleic acid (DNA) mutations that impair the respiratory chain. These include, but are not limited to the following clinical syndromes: Leber's hereditary optic neuropathy; myoclonic epilepsy and ragged-red fibers (MERFF); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS); Kearn-Sayre syndrome; subacute necrotizing encephalopathy (Leigh Syndrome); polymerase gamma (POLG)-related disorders (Alpers-Huttenlocher Syndrome, Autosomal Dominant Progressive External Ophthalmoplegia, Autosomal Recessive Progressive External Ophthalmoplegia, Childhood Myocerebrohepatopathy Spectrum Disorders, Myoclonic Epilepsy Myopathy Sensory Ataxia, POLG-Related Ataxia Neuropathy Spectrum Disorders); Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE), also called myoneurogastrointestinal encephalopathy syndrome or polyneuropathy-ophthalmoplegia-leukoencephalopathy- Intestinal pseudoobstruction (POLIP) syndrome; others, e.g., mitochondrial cardiomyopathies and other syndromes due to multiple mitochondrial DNA deletions.

Patients completing study RP103-MITO-001 (NCT02023866) are eligible for enrollment into the extension study RP103-MITO-002 if all inclusion and exclusion criteria are fulfilled. Subjects continue on the last total daily dose of cysteamine bitartrate delayed-release capsules taken during RP103-MITO-001. Dose-adjustments are permitted.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label extension study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mitochondrial Diseases
Intervention  ICMJE Drug: Cysteamine Bitartrate
Cysteamine Bitartrate Delayed-release capsules
Other Names:
  • RP103
Study Arms  ICMJE Experimental: Cysteamine Bitartrate Delayed-release
Participants received cysteamine bitartrate delayed-release capsules (RP103) twice daily for up to 2 years. The starting dose was the same as the last dose received in study RP103-MITO-001, the maximum dose was 1.3 g/m²/day.
Intervention: Drug: Cysteamine Bitartrate
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 16, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: June 11, 2015)
Actual Study Completion Date  ICMJE March 6, 2017
Actual Primary Completion Date March 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Completed all visits in Study RP103-MITO-001 (NCT02023866).
  2. Body weight ≥ 5 kg.
  3. The subject must be willing to abstain from initiating dietary supplements and non-prescribed medications except as allowed by the Investigator, throughout the study (from Day 1 to Study Exit).
  4. Willing and able to comply with study drug dosing requirements, i.e. ingest the RP103 capsules intact, or sprinkled in liquid or soft food, or using a G-tube.
  5. Sexually active female subjects of childbearing potential (i.e., not surgically sterile [tubal ligation, hysterectomy, or bilateral oophorectomy]) must agree to utilize two of the following acceptable forms of contraception throughout the study (from Day 1 to Study Exit):

    • Hormonal contraception: birth control pills, injection, patch, vaginal ring or implant;
    • Condom or diaphragm, with spermicide;
    • Intrauterine device (IUD);
    • Sterile male partner (vasectomy performed at least 6 months prior to the study).
  6. Patient's legally authorized representative must provide written informed consent; Patient must provide assent, if required by local/institutional requirements.

Exclusion Criteria:

  1. Documented diagnosis of concurrent inborn errors of metabolism.
  2. Platelet count, lymphocyte count or hemoglobin below the lower limit of normal (LLN) at the Baseline visit.
  3. Hepatic insufficiency with liver enzyme tests (alkaline phosphatase, aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) greater than 2.5 times the upper limit of normal (ULN) at the Baseline Visit.
  4. Bilirubin > 1.2 g/dL at the Baseline Visit.
  5. Inability to complete the elements of the study, e.g., coma, hemodynamic instability or requiring continuous ventilator support.
  6. Malabsorption requiring total parenteral nutrition (TPN), chronic diarrhea, bouts of pseudo obstruction.
  7. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis.
  8. Patients with suspected elevated intracranial pressure, pseudotumor cerebri (PTC) and/or papilledema.
  9. Severe gastrointestinal disease including gastroparesis.
  10. History of drug or alcohol abuse.
  11. History of pancreatitis.
  12. Participated in an investigational drug trial (except the RP103-MITO-001 study) within 30 days or, within 90 days for a biologic, device, or surgical treatment, for inherited mitochondrial diseases prior to the Baseline Visit.
  13. Known or suspected hypersensitivity to cysteamine and penicillamine.
  14. Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or with a positive serum pregnancy test at the Baseline visit.
  15. Patients who, in the opinion of the Investigator, are not able or willing to comply with the protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02473445
Other Study ID Numbers  ICMJE RP103-MITO-002
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 April 2018

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