Trial record 1 of 1 for:    "medium-chain acyl-coenzyme a dehydrogenase deficiency"
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Use of Ravicti™ in Patients With MCAD Deficiency With the 985A>G (K304E) Mutation

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Hyperion Therapeutics, Inc.
Information provided by (Responsible Party):
Gerard Vockley, MD, PhD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01881984
First received: June 13, 2013
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

This is a medical research study to test a medication in adult patients with a disease called medium-chain acyl-CoA dehydrogenase (MCAD) deficiency caused by the 985A>G mutation. The medication is glycerol phenylbutyrate, called Ravicti, which is currently FDA approved for the treatment of urea cycle disorders. Previous research suggests that Ravicti may also be effective in the treatment MCAD deficiency. This study will investigate the safety and efficacy (how well it works) of Ravicti in patients with MCAD deficiency caused by the 985A>G mutation.


Condition Intervention Phase
Medium-chain Acyl-CoA Dehydrogenase (MCAD) Deficiency
Drug: Ravicti
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Use of Glycerol Phenylbutyrate (Ravicti™) as a Chaperone to Stabilize Enzyme in Patients With MCAD Deficiency Due to the Common MCAD 985A>G (K304E) Mutation

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Metabolic stress [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]
    Changes in the assessments of metabolic stress pre- and post-dosing with Ravicti will be the main outcome variable.


Secondary Outcome Measures:
  • Pharmacokinetic (pK)analysis [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]
    Results from the pharmacokinetic (pK)analysis (the rate of conversion of the phenylbutyrate to phenylacetate) will also be reviewed to assess for changes pre- and post-dosing with Ravicti as well as changes in these levels at the different doses of Ravicti.


Estimated Enrollment: 6
Study Start Date: June 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ravicti Drug: Ravicti
Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day
Other Name: glycerol phenylbutyrate

Detailed Description:

Participation in the study will require one overnight admission and three outpatient visits at the Clinical and Translational Research Center at Children's Hospital of Pittsburgh of UPMC (also called the PCTRC). The total length of the study is 7 weeks.

Subjects will have blood work and an intravenous access line (IV) placed for several blood draws during the visit. Subjects will begin fasting at 8pm during the admission, which means they may consume only non-caloric fluids (water, unsweetened black coffee or tea, or sugar-free beverages). The next morning, fasting blood work will be obtained. The subject can then eat breakfast and will receive the study drug, Ravicti. The total time of fasting will be 12 hours.

Dosing for this study will begin at 2 grams/m2/day, which is about one-fifth (1/5) the dose used for other disorders. The reason for starting the dose lower in MCAD patients is that Ravicti is metabolized by the MCAD enzyme. Following the initial dose, blood will be drawn from the IV every two hours for 8 hours. These blood studies will check the levels of Ravicti in the subject's blood and monitor how the subject's body metabolizes them. The subject will be discharged 8 hours after drug administration. Following discharge, the subject will take Ravicti every day for two weeks.

Visit 2: After two weeks at a dose of 2 grams/m2/day, the subject will fast after 8 PM, and will come to the PCTRC the following morning to have an IV placed and blood draws. If the subject's blood work from the first visit shows that there is no concern, the subject's dose will be increased to 4 grams/m2/day. The subject will receive the first dose at this level in the PCTRC with breakfast, and blood samples will be collected from the IV every 2 hours for the next 8 hours. The subject will continue on this dose for two weeks.

Visit 3: After two weeks at a dose of 4 grams/m2/day, the subject will fast after 8 PM, and will come to the PCTRC the following morning to have an IV placed and blood draws. If the subject's blood work from the previous visit shows that there is no concern, the subject's dose will be increased to 6 grams/m2/day. The subject will receive the first dose at this level in the PCTRC with breakfast, and blood samples will be collected from the IV every 2 hours for the next 8 hours. The subject will continue on this dose for two weeks.

Visit 4 (final): After two weeks at a dose of 6 grams/m2/day, the subject will fast after 8 PM, and will come to the CTRC the following morning to have one blood draw. The subject will return any unused Ravicti, and their study participation will be completed.

All study procedures will be done at no cost to the subjects.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • confirmation of a diagnosis of MCAD deficiency
  • two copies of 985A>G MCAD mutation
  • ability to follow protocol

Exclusion Criteria:

  • positive pregnancy test
  • currently breastfeeding
  • currently taking any medication for which there is a potential drug interaction with Ravicti, includes corticosteroids, valproic acid, haloperidol, and probenecid
  • liver or kidney insufficiency
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01881984

Contacts
Contact: Elizabeth McCracken, MS, CGC 412-692-5662 elizabeth.mccracken@chp.edu

Locations
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Elizabeth McCracken, MS, CGC    412-692-5662    elizabeth.mccracken@chp.edu   
Principal Investigator: Gerard Vockley, MD, PhD         
Sub-Investigator: Georgianne Arnold, MD         
Sub-Investigator: Areeg El-Gharbawy, MD         
Sponsors and Collaborators
University of Pittsburgh
Hyperion Therapeutics, Inc.
Investigators
Principal Investigator: Gerard Vockley, MD, PhD University of Pittsburgh/Children's Hospital of Pittsburgh of UPMC
  More Information

Additional Information:
Publications:
Responsible Party: Gerard Vockley, MD, PhD, Professor of Pediatrics/Human Genetics, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01881984     History of Changes
Other Study ID Numbers: PRO13050530
Study First Received: June 13, 2013
Last Updated: March 17, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Medium-chain acyl-CoA dehydrogenase deficiency
MCAD deficiency
MCADD
ACADM deficiency
MCADH deficiency
985A>G mutation
K304E mutation
Ravicti
glycerol phenylbutyrate

Additional relevant MeSH terms:
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Metabolic Diseases
Glycerol
4-phenylbutyric acid
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014