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

Overview

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

Full Title of Study: “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

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: February 28, 2020

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.

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.

Interventions

  • Other: Sodium Acetate
    • Used as a tracer to measure the rate of ureagenesis

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Plasma Ammonia Area Under the Curve (AUC0-24)
    • Time Frame: 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
  • Rate of Ureagenesis Based On Presence of [1-13C] In Urea
    • Time Frame: 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
  • Intra- and inter-subject coefficient of variation (CV) of AUC0-24 and Rate of Ureagenesis
    • Time Frame: Part 1 Treatment Period: 17 days; Part 2 Treatment Period: 3 days
    • Comparative analysis of both parameters

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Ultragenyx Pharmaceutical Inc
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Director, Study Director, Ultragenyx Pharmaceutical
  • Overall Contact(s)
    • Patients Contact: Patient Advocacy, 1-415-483-8800, patientadvocacy@ultragenyx.com

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