Acetaldehyde Toxicity Clinical Trial
Official title:
Phase IIa, Prospective, Randomized, Blinded, Intra-Subject Controlled, Dose Escalation Study of Fomepizole for Mitigation of Acetaldehyde Related Toxicity in Human Subjects With Altered Ethanol Metabolism With Concomitant Ethanol Exposure
This trial will evaluate if fomepizole (4-methylpyrazole)can treat symptoms associated with alcohol intolerance due to aldehyde dehydrogenase 2 (ALDH2) Deficiency, an inherited metabolic disorder. These symptoms include flushing, nausea, headache, shortness of breath and dizziness, resulting from exposure to acetaldehyde, the primary metabolite of ethanol. Long-term, serious health risks have been associated with repeated exposure to acetaldehyde, a carcinogen, among ALDH2-deficient individuals.
Approximately 32 subjects will be enrolled in ascending dosing cohorts of 8 subjects each. Each subject will receive an oral dose of study drug (fomepizole or placebo) with concomitant ethanol with group assignment in a randomized 1:1:1:1 ratio (2 subjects each group) on Study Day 1. Each subject is their own intra-subject control with the alternative study drug (fomepizole or placebo) administered on the next day (Study Day 2). Four subjects in each cohort will receive study drug (fomepizole or placebo) administered 30 minutes prior to ethanol, 4 with study drug (fomepizole or placebo) administered 30 minutes after ethanol. The study will assess safety and tolerability of fomepizole and the PK/PD of 4-MP, ethanol and acetaldehyde in the subject population. ;
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment