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

NCT ID: NCT01881984

Last Updated: 2017-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2016-02-29

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.

Conditions

Medium-chain Acyl-CoA Dehydrogenase (MCAD) Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ravicti

Open Label Study

Group Type: EXPERIMENTAL

Ravicti

Intervention Type: DRUG

Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day

Interventions

Ravicti

Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day

Intervention Type: DRUG

Other Intervention Names

glycerol phenylbutyrate

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Horizon Pharma Ireland, Ltd., Dublin Ireland

INDUSTRY

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Gerard Vockley, MD, PhD

Professor of Pediatrics/Human Genetics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gerard Vockley, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh/Children's Hospital of Pittsburgh of UPMC

Locations

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23141465 (View on PubMed)

Related Links

http://ghr.nlm.nih.gov/condition/medium-chain-acyl-coa-dehydrogenase-deficiency

U.S. National Library of Medicine Genetics Home Reference Information on MCAD Deficiency

Other Identifiers

PRO13050530

Identifier Type: -

Identifier Source: org_study_id