Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Use of Ravicti™ in Patients With MCAD Deficiency With the 985A>G (K304E) Mutation

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: NCT01881984
Recruitment Status : Completed
First Posted : June 20, 2013
Results First Posted : July 11, 2017
Last Update Posted : September 25, 2017
Sponsor:
Collaborator:
Horizon Pharma Ireland, Ltd., Dublin Ireland
Information provided by (Responsible Party):
Gerard Vockley, MD, PhD, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE June 13, 2013
First Posted Date  ICMJE June 20, 2013
Results First Submitted Date  ICMJE February 14, 2017
Results First Posted Date  ICMJE July 11, 2017
Last Update Posted Date September 25, 2017
Study Start Date  ICMJE June 2013
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2013)
Metabolic Stress [ Time Frame: 7 weeks ]
Changes in the assessments of metabolic stress pre- and post-dosing with Ravicti will be the main outcome variable.
Original Primary Outcome Measures  ICMJE
 (submitted: June 17, 2013)
Changes in the assessments of metabolic stress [ Time Frame: 7 weeks ]
Changes in the assessments of metabolic stress (free fatty acids, acylcarnitine intermediates, ketones, fasting glucose, acylglycines) pre- and post-dosing with Ravicti will be the main outcome variable.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2013)
Pharmacokinetic (pK)Analysis [ Time Frame: 7 weeks ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2013)
Results from the pharmacokinetic (pK)analysis (the rate of conversion of the phenylbutyrate to phenylacetate) [ Time Frame: 7 weeks ]
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. A pre-dose sample will be collected at each visit which will be compared to the post-dosing pK samples to establish the rate at which the subject converts the phenylbutyrate to phenylacetate.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Use of Ravicti™ in Patients With MCAD Deficiency With the 985A>G (K304E) Mutation
Official Title  ICMJE 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
Brief Summary 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 at least one copy of 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 having at least one copy of the 985A>G mutation.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Medium-chain Acyl-CoA Dehydrogenase (MCAD) Deficiency
Intervention  ICMJE Drug: Ravicti
Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day
Other Name: glycerol phenylbutyrate
Study Arms  ICMJE Experimental: Ravicti
Open Label Study
Intervention: Drug: Ravicti
Publications * Kormanik K, Kang H, Cuebas D, Vockley J, Mohsen AW. Evidence for involvement of medium chain acyl-CoA dehydrogenase in the metabolism of phenylbutyrate. Mol Genet Metab. 2012 Dec;107(4):684-9. doi: 10.1016/j.ymgme.2012.10.009. Epub 2012 Oct 18.

*   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: March 1, 2016)
4
Original Estimated Enrollment  ICMJE
 (submitted: June 17, 2013)
6
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • confirmation of a diagnosis of MCAD deficiency
  • at least one copy 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01881984
Other Study ID Numbers  ICMJE PRO13050530
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gerard Vockley, MD, PhD, University of Pittsburgh
Study Sponsor  ICMJE University of Pittsburgh
Collaborators  ICMJE Horizon Pharma Ireland, Ltd., Dublin Ireland
Investigators  ICMJE
Principal Investigator: Gerard Vockley, MD, PhD University of Pittsburgh/Children's Hospital of Pittsburgh of UPMC
PRS Account University of Pittsburgh
Verification Date September 2017

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