Clinical trial NCT04269122: A Study to Assess Plasma Ammonia Time-Normalized Area Under the Curve and Rate of Ureagenesis in Healthy Adult Subjects
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ornithine Transcarbamylase Deficiency
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2020-02-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy Volunteers at a Phase 1 unit

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Plasma Ammonia Area Under the Curve (AUC0-24)
timeFrame: Part 1, Day 1 (Visits 1-3) and Part 2, Day 1:Predose (0hour) up to 24 hours post dose
measure: Rate of Ureagenesis Based On Presence of [1-13C] In Urea
timeFrame: Part 1, Day 1 (Visits 1-3) and Part 2, Day 1: Predose (0hour) up to 4 hours post dose
measure: Intra- and inter-subject coefficient of variation (CV) of AUC0-24 and Rate of Ureagenesis
timeFrame: Part 1 Treatment Period: 17 days; Part 2 Treatment Period: 3 days
Secondary outcomes:
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Phase 1 Unit
state: Texas
Study officials:
affiliation: Ultragenyx Pharmaceutical
name: Medical Director
role: STUDY_DIRECTOR
References: