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.

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.

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.