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

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

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

Study Overview

• Status: Completed
• Conditions: Ornithine Transcarbamylase Deficiency
• Intervention / Treatment: Other: No Intervention

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 Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Phase 1 Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy Volunteers at a Phase 1 unit

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Part 1; 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.	Other: No Intervention; No intervention
Part 2; 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.	Other: No Intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2019
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): February 20, 2020

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Actual): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease
• Other Study ID Numbers: 301NHV01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No