Use of Ravicti™ in Patients With MCAD Deficiency With the 985A>G (K304E) Mutation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ravicti Open Label Study |
Drug: Ravicti
Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Metabolic Stress [7 weeks]
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 [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.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
Sponsors and Collaborators
- University of Pittsburgh
- Horizon Pharma Ireland, Ltd., Dublin Ireland
Investigators
- Principal Investigator: Gerard Vockley, MD, PhD, University of Pittsburgh/Children's Hospital of Pittsburgh of UPMC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- PRO13050530
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ravicti |
|---|---|
| Arm/Group Description | Open Label Study Ravicti: Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day |
| Period Title: Overall Study | |
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Ravicti |
|---|---|
| Arm/Group Description | Open Label Study Ravicti: Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day |
| Overall Participants | 4 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
4
100%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
100%
|
| Male |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
4
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
4
100%
|
Outcome Measures
| Title | Metabolic Stress |
|---|---|
| Description | Changes in the assessments of metabolic stress pre- and post-dosing with Ravicti will be the main outcome variable. |
| Time Frame | 7 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the small sample size in this Phase I study, details on the analysis cannot be provided due to concerns with subject confidentiality. |
| Arm/Group Title | Ravicti |
|---|---|
| Arm/Group Description | Open Label Study Ravicti: Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day |
| Measure Participants | 0 |
| Title | Pharmacokinetic (pK)Analysis |
|---|---|
| Description | 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. |
| Time Frame | 7 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the small sample size in this Phase I study, details on the analysis cannot be provided due to concerns with subject confidentiality. |
| Arm/Group Title | Ravicti |
|---|---|
| Arm/Group Description | Open Label Study Ravicti: Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Approximately 7 weeks | |
|---|---|---|
| Adverse Event Reporting Description | The definition of adverse event and a serious adverse event used to collect this information did not differ from the clinicaltrials.gov definition. | |
| Arm/Group Title | Ravicti | |
| Arm/Group Description | Open Label Study Ravicti: Open-label design comparing Ravicti at doses of 2, 4, and 6 grams/m2/day | |
All Cause Mortality |
||
| Ravicti | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | |
Serious Adverse Events |
||
| Ravicti | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Ravicti | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/4 (75%) | |
| Gastrointestinal disorders | ||
| Dry mouth | 1/4 (25%) | 1 |
| Nausea | 2/4 (50%) | 2 |
| Vomiting | 1/4 (25%) | 1 |
| Investigations | ||
| Elevated PBA level | 2/4 (50%) | 2 |
| Musculoskeletal and connective tissue disorders | ||
| Neck pain | 1/4 (25%) | 1 |
| Nervous system disorders | ||
| Decreased reflexes | 1/4 (25%) | 1 |
| Vascular disorders | ||
| Thromboembolic event | 1/4 (25%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Gerard Vockley |
|---|---|
| Organization | University of Pittsburgh |
| Phone | 412-692-7746 |
| gerard.vockley@chp.edu |
- PRO13050530