Status:
COMPLETED
Phase IIa Study of Fomepizole for Acetaldehyde Toxicity After Ethanol Exposure in Subjects With Altered Ethanol Metabolism
Lead Sponsor:
Amgen
Conditions:
Aldehyde Dehydrogenase-2 (ALDH2) Deficiency
Eligibility:
All Genders
21-50 years
Phase:
PHASE2
Brief Summary
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. Th...
Detailed Description
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 gr...
Eligibility Criteria
Inclusion
- Signed informed consent
- Age 21 to 50 years
- Subject of Japanese descent
- History of flushing, with or without palpitations, or nausea (Alcohol Sensitivity Screening Test ≥ 3.1) following occasional or inadvertent ethanol consumption either currently or in the past
- Subjects must be healthy volunteers with no other clinically relevant abnormalities as determined by medical history, blood chemistry, complete blood count (CBC), urinalysis,and 12-lead electrocardiogram (ECG)
- Positive skin ethanol patch test (100 μL of 70% ethanol on a lint pad applied to skin for 7 minutes results in an area of erythema)
- For Cohort 4, enrolled subjects were either homozygous or heterozygous for the ALDH2\*2 genotype as assessed by genotyping at Screening
Exclusion
- Vaccination within 2 weeks of Day 1
- Current respiratory disease or a past history of chronic respiratory disease, or current smoker within last six months
- Any one of the following Screening ECG findings:
- QTc (Bazett) interval duration greater than 450 msec (male) or 470 msec (female), or
- QRS interval greater than 120 msec, or
- PR interval greater than 220 msec
- History or evidence of drug or alcohol abuse or regular consumption of more than 8 units of alcohol daily (1 unit = 300 mL beer, 1 glass wine, 1 measure spirit) or those who may have difficulty abstaining from non study alcohol during the 36 hours prior to dose administration and until completion of blood sampling on Day 7
- Subjects who have donated blood totalling more than 550 mL within the 3 months prior to Day 1
- Use of any prescription medication other than oral contraceptives during the 14 days prior to Day 1, unless approved by both the Principal Investigator (PI) and the Sponsor
- Inability to abstain from smoking any tobacco product from within prior to 2 hours of blood sampling to after 2 hours of blood sampling during the study period.
- Use of any over-the-counter product, herbal product, diet aid, hormone supplement, etc., within 14 days prior to Day 1 unless approved by both the PI and the Sponsor
- Chronic use of pain medications
- Administration of an investigational agent within the last 30 days (or within a period of less than 5 times the agent's half-life, whichever is longer) prior to Day 1
- Major surgery within 60 days prior to Day 1, or any planned surgery or medical procedure during the study period (through Day 7)
- Positive alcohol breath-test or Positive drug screen (e.g., opiates, barbiturates, cannabinoids, benzodiazepines, cocaine, amphetamines) during screening or at Day 0 Check-In
- Known hypersensitivity reaction to Antizol® or other pyrazoles, tomato juice
- Abnormal laboratory results, including:
- WBC ≤3.5 × 109/L or neutrophil count ≤2.0 × 10\^9/L
- Hemoglobin \<12.0 or \>16.0 gm/dL
- Creatinine ≥2 mg/dL
- Total bilirubin ≥2 mg/dL
- Alanine aminotransferase and/or aspartate aminotransferase ≥2 times the upper limit of normal
- PaO2 ≤95% on room air by pulse oximetry
- Urine dipstick positive for protein, blood, ketones, glucose or leukocyte esterase
- Any other clinically significant abnormal result for hematology, clinical chemistry, or urinalysis at screening or check-In
- Positive serum pregnancy test for females of childbearing potential
- Subject and/or partner unable or unwilling to use an effective form of barrier contraceptives during the course of the study and for 7 days after study drug administration.
- Cancer (excluding adequately treated basal cell carcinoma) within the last 5 years
- Significant past medical history of hepatic, renal, cardiovascular (including family history of prolonged QT syndrome), pulmonary, gastrointestinal, hematological, locomotor, immunologic, ophthalmologic, metabolic endocrine or other diseases; or any condition that in the opinion of the Investigator would complicate or compromise the study, or the well-being of the subject
- Any other reason, which in the opinion of the Principal Investigator, would prevent the subject from completing or following the study schedule
Key Trial Info
Start Date :
April 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 1 2008
Estimated Enrollment :
32 Patients enrolled
Trial Details
Trial ID
NCT00661141
Start Date
April 1 2008
End Date
June 1 2008
Last Update
December 27 2024
Active Locations (1)
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1
Covance Honolulu CRU
Honolulu, Hawaii, United States, 96813