Ornithine Transcarbamylase Deficiency
Conditions
Brief summary
The objective of the study is to characterize 24-hour plasma ammonia levels, characterize urea production rates in healthy normal subjects.
Detailed description
During Part 1, eligible subjects will be asked to participate in 3 inpatient visits, each lasting up to 3 days (Day -1 to Day 2). Each visit will assess 24-hour ammonia levels in plasma and rate of urea production for 4 hours following ingestion of \[1-13C\]sodium acetate. Sodium acetate is used as a tracer to measure the rate of ureagenesis. During Part 2, eligible subjects will be asked to participate in 1 inpatient visit, lasting up to 3 days (Day -1 to Day 2). The visit will assess 24-hour ammonia levels in plasma and rate of urea production for 4 hours following ingestion of \[1-13C\]sodium acetate. Sodium acetate is used as a tracer to measure the rate of ureagenesis.
Interventions
OTHERNo Intervention
No intervention
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index between 18 and 30 kg/m2, inclusive.
Exclusion criteria
* History of liver disease as evidenced by any of the following: portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, or a liver biopsy with evidence of stage 3 fibrosis. * Significant hepatic inflammation or cirrhosis as evidenced by imaging or any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than the upper limit of normal (ULN), total bilirubin \>1.5 × ULN, alkaline phosphatase \>2.5 × ULN. NOTE: the ALT and/or AST levels may be repeated. * Subject has a history of gout. * Plasma ammonia level that is not within normal limits at Screening in the opinion of the Investigator or Sponsor. * Received any vaccine within 14 days prior to Screening. * Pregnant, lactating, or intending to become pregnant at any time during the study. * Blood transfusion within 8 weeks prior to Screening.diuretics, cyclophosphamide and other cytotoxic agents, tolbutamide, chlorpropamide, diazoxide, dichlorphenamide, pyrazinamide, probenecid, theophylline/aminophylline, riluzole, warfarin and other antithrombotic agents, supplements containing aluminum hydroxide, or iron supplements within 30 days of Part 1or Part 2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Ammonia Area Under the Curve (AUC0-24) | Part 1, Day 1 (Visits 1-3) and Part 2, Day 1:Predose (0hour) up to 24 hours post dose | Characterization of ammonia production over 24hr |
| Rate of Ureagenesis Based On Presence of [1-13C] In Urea | Part 1, Day 1 (Visits 1-3) and Part 2, Day 1: Predose (0hour) up to 4 hours post dose | Characterization of nitrogen flux as determined by production of urea. Sodium acetate is used as a tracer to measure the rate of ureagenesis. |
| Intra- and inter-subject coefficient of variation (CV) of AUC0-24 and Rate of Ureagenesis | Part 1 Treatment Period: 17 days; Part 2 Treatment Period: 3 days | Comparative analysis of both parameters |
Countries
United States
Outcome results
None listed