UMIN-CTR Clinical Trial

Public title

Single Blind, Placebo-Controlled Study of Acetaminophen for Liver function in Healthy Japanese Adults

Acronym

Study of Acetaminophen on Shift of Liver Function Markers

Scientific Title

Single Blind, Placebo-Controlled Study of Acetaminophen for Liver function in Healthy Japanese Adults

Scientific Title:Acronym

Study of Acetaminophen on Shift of Liver Function Markers

Region

Japan

Condition

Drug-induced liver injury (DILI)

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Others

Genomic information

YES

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

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)

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Yuji Kumagai

Organization

Kitasato University Hospital

Division name

Clinical trial Center

Zip code

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

Name of contact person

1st name
Middle name
Last name	Rieko Tanaka

Organization

Kitasato University School of Medicine

Division name

Kitasato Clinical Research Center

Zip code

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

Institute

Kitasato Clinical Trial Center

Institute

Department

Personal name

Organization

AMED

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Co-sponsor

National Institute of Health Sciences
Kihara Memorial Yokohama Foundation

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

北里大学病院臨床試験センター（神奈川県）

Date of disclosure of the study information

2015

Year

11

Month

18

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2015

Year

11

Month

18

Day

Date of IRB

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

Other related information

Registered date

2015

Year

11

Month

02

Day

Last modified on

2016

Year

12

Month

15

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022631