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

Ornithine Transcarbamylase Deficiency Clinical Trial

Official title:

A Single-Center Study to Assess Plasma Ammonia Time-Normalized Area Under the Curve From Time Zero to 24 Hours and Rate of Ureagenesis in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04269122
• Other study ID #: 301NHV01
• Status: Completed
• Start date: August 2, 2019
• Est. completion date: February 20, 2020

Study information

• Verified date: March 2020
• Source: Ultragenyx Pharmaceutical Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of the study is to characterize 24-hour plasma ammonia levels, characterize urea production rates in healthy normal subjects.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: February 20, 2020
• Est. primary completion date: February 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ornithine Transcarbamylase Deficiency

Intervention

Other:
• No Intervention
No intervention

Locations

Country	Name	City	State
United States	PPD Phase 1 Unit	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Ammonia Area Under the Curve (AUC0-24)	Characterization of ammonia production over 24hr	Part 1, Day 1 (Visits 1-3) and Part 2, Day 1:Predose (0hour) up to 24 hours post dose
Primary	Rate of Ureagenesis Based On Presence of [1-13C] In Urea	Characterization of nitrogen flux as determined by production of urea. Sodium acetate is used as a tracer to measure the rate of ureagenesis.	Part 1, Day 1 (Visits 1-3) and Part 2, Day 1: Predose (0hour) up to 4 hours post dose
Primary	Intra- and inter-subject coefficient of variation (CV) of AUC0-24 and Rate of Ureagenesis	Comparative analysis of both parameters	Part 1 Treatment Period: 17 days; Part 2 Treatment Period: 3 days