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

NCT04269122 | Completed FDA Drug

• 1 other identifier: 301NHV01
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Ornithine Transcarbamylase Deficiency

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

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

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

Interventions

No Intervention OTHER

No intervention

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy Volunteers at a Phase 1 unit

You may qualify if:

• Body mass index between 18 and 30 kg/m2, inclusive.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (1)

PPD Phase 1 Unit

Austin, Texas, 78744, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine and plasma

MeSH Terms

Conditions

Ornithine Carbamoyltransferase Deficiency Disease

Condition Hierarchy (Ancestors)

Urea Cycle Disorders, Inborn; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 13, 2020
• Study Start: August 2, 2019
• Primary Completion: February 20, 2020
• Study Completion: February 20, 2020
• Last Updated: March 30, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)