A Study to Assess Plasma Ammonia Time-Normalized Area Under the Curve and Rate of Ureagenesis in Healthy Adult Subjects

Completed

• Conditions: Ornithine Transcarbamylase Deficiency
• Interventions: Other: No Intervention

• Registration Number: NCT04269122
• Lead Sponsor: Ultragenyx Pharmaceutical Inc

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.

Study Timeline

• Study Start: 2019-08-02
• Study First Submitted: 2020-02-10
• Study First Submitted QC: 2020-02-11
• Study First Posted: 2020-02-13
• Primary Completion: 2020-02-20
• Study Completion: 2020-02-20
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-27
• Last Update Posted: 2020-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Part 2	No Intervention	90 eligible subjects will be asked to participate in 1 inpatient visit, 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.
Part 1	No Intervention	30 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.

Primary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

PPD Phase 1 Unit; 🇺🇸 Austin, Texas, United States