UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Single Blind, Placebo-Controlled Study of Acetaminophen for Liver function in Healthy Japanese Adults
Title of the study (Brief title)	Study of Acetaminophen on Shift of Liver Function Markers
Region	Japan

Condition
Condition	Drug-induced liver injury (DILI)
Classification by specialty	Hepato-biliary-pancreatic medicine
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	Primary Objective: This study aims to evaluate the effect of acetaminophen (1,000 mg three times a day for four weeks) for pharmacokinetics, safety and liver function markers in healthy Japanese adults. The objective is not detections of clinical liver function but detections of novel biomarkers correlated with known markers. Secondary Objective: When continuous dosing of acetaminophen (1,000 mg at a time, three times a day) are given to Japanese healthy adults for 28 days, the causation with the background factor is examined in the subjects that a change of the liver function biomarker was observed.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Not applicable

Assessment
Primary outcomes	Biomarker for liver function ALT, AST, ALP, u-GTP, Total bilirubin, Direct bilirubin
Key secondary outcomes	(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)

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Single blind -participants are blinded
Control	Placebo
Stratification	YES
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Diagnosis
Type of intervention	Medicine
Interventions/Control_1	Acetaminophen (1,000 mg three times a day for 28 days)
Interventions/Control_2	Placebo (lactose, three times a day for 28 days)
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	45 years-old >=
Gender	Male and Female
Key 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.
Key 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.
Target sample size	240

Research contact person
Name of lead principal investigator	Yuji Kumagai
Organization	Kitasato University Hospital
Division name	Clinical trial Center
Address	1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, 252-0375 Japan
TEL	042-778-9965
Email	kuma-guy@za2.so-net.ne.jp

Public contact
Name of contact person	Rieko Tanaka
Organization	Kitasato University School of Medicine
Division name	Kitasato Clinical Research Center
Address	1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, 252-0375 Japan
TEL	042-778-9547
Homepage URL
Email	rieko_t@med.kitasato-u.ac.jp

Sponsor
Institute	Kitasato Clinical Trial Center
Institute
Department

Funding Source
Organization	AMED
Organization
Division
Category of Funding Organization
Nationality of Funding Organization

Other related organizations
Co-sponsor	National Institute of Health Sciences Kihara Memorial Yokohama Foundation
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	北里大学病院臨床試験センター（神奈川県）

Other administrative information
Date of disclosure of the study information	2015 Year 11 Month 18 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 11 Month 18 Day
Anticipated trial start date	2015 Year 12 Month 01 Day
Last follow-up date	2016 Year 03 Month 31 Day
Date of closure to data entry	2016 Year 10 Month 19 Day
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 11 Month 02 Day
Last modified on	2016 Year 12 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022631