Drug-induced liver injury (DILI)
Conditions
Interventions
Acetaminophen (1,000 mg three times a day for 28 days)
Placebo (lactose, three times a day for 28 days)
Sponsors
Kitasato Clinical Trial Center
National Institute of Health Sciences Kihara Memorial Yokohama Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for inclusion in this study have to fulfill all of following criteria and be judged eligible for the study by the investigator. 1) Those who have ability to provide written consent to participate in the study. 2) Healthy male subjects between the ages of 20 and 45 years at the time of obtaining informed consent. 3) Body weight between 50 kg and 100 kg (between 45 kg and 80 kg in female) and a body mass index (BMI) between 18 and 27 kg/m2. 4) AST and ALT values are within upper limits normal of trial site pasility. 5) Judged to be healthy by the study physician based on medical examinations and clinical laboratory tests. 6) It is a condition that grandparents are Japanese.
Exclusion criteria
Exclusion criteria: Subjects will be excluded from enrollment by the following criteria. The investigator must ensure the criteria basically at the timing of screening. 1) Any subject with a past history of anaphylaxis due to acetaminophen. 2) Any subject with peptic ulcer. 3) Any subject with blood abnormality, hepatopathy, kidney damage or cardiac dysfunction. 4) Aspirin-induced asthma or a history of diseases of aspirin-induced asthma. 5) Alcohol drinkers (daily alcohol intake of 30 g or more in the past 3 months). 6) Use of any medicine, energy drink and health food product containing Saint John's wort or use of a drug within 14 days before study drug administration. 7) Participation in any other clinical trial within the past 12 weeks. 8) Persons who have donated more than 200 ml of blood in the past 4 weeks or more than 400 ml of blood in the past 12 weeks (more than 200 ml of blood in the past 4 weeks or more than 400 ml of blood in the past 16 weeks in female). 9) Any subject with a positive serological response for syphilis, HIV antigen or antibody, HBs antigen, or HCV antibody. 10) Any subject have drug or food allergies. 11) Any subject known to abuse drugs or who tests positive for a drug in urine screening tests. 12) Women who are pregnant, maybe pregnant or lactation. 13) Any condition that, in the opinion of the investigator, would make the patient unsuitable for inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Biomarker for liver function ALT, AST, ALP, u-GTP, Total bilirubin, Direct bilirubin | — |
Secondary
| Measure | Time frame |
|---|---|
| (1) Pharmacokinetics Plasma concentration of unchanged acetaminophen, Urinary concentration of acetaminophen metabolite and Pharmacokinetic parameters (2) Safety Adverse events Vital sign, Electrocardiogram, and Laboratory evaluations (3) Candidate Biomarker for liver function Glutamate dehydrogenase (GLDH), Malate dehydrogenase (MDH), Paraoxonase (PON-1), Purine nucleoside phosphorylase (PNP), Arginase-1 (ARG-1), Sorbitol dehydrogenase (SDH), GSTa, miR-122, High mobility group box-1(HMGB-1), Keratin-18 (4)Background Background of subject, Polymorphism (CYP2E1, UGT1A1) | — |
Countries
Japan
Contacts
Public ContactRieko Tanaka
Kitasato University School of Medicine Kitasato Clinical Research Center
Outcome results
None listed