UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Study for drug-drug interactions involving hepatic OATPs using its endogenous substrates
Title of the study (Brief title)	OATP endogenous substrate-interaction study
Region	Japan

Condition
Condition	Healthy volunteers (Japanese male)
Classification by specialty	Adult
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	Quantitative analysis for interactions between OATP endogenous substrates, statins (atorvastatin, fluvastatin, pitavastatin, and rosuvastatin) and rifampicin via hepatic OATPs in Japanese healthy male adults
Basic objectives2	PK,PD
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Plasma and urinary concentrations of coproporphyrins, DHEAS, bilirubin and its glucuronides, bile acids (including glucuronide and sulfate conjugates), and 7a-hydroxy-4-cholesten-3-one, effect of the administration of rifampicin Plasma and urinary concentrations of atorvastatin, fluvastatin, pitavastatin, rosuvastatin, and rifampicin, and their metabolites, effect of the coadministration of rifampicin, pharmacokinetic parameters
Key secondary outcomes	SNPs of drug-metabolizing enzymes and transporters relating pharmacokinetics (OATP1B1, CYP3A4, CYP2C8, CYP2C9)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Drug administration (semi-pharmacological dose of atorvastatin, fluvastatin, pitavastatin, and rosuvastatin) -> (over 1week for washout) -> Drug administration(clinical dose of rifampicin (300 mg), and semi-pharmacological dose of atorvastatin, fluvastatin, pitavastatin, and rosuvastatin) -> (over 1week for washout) -> Drug administration (clinical dose of rifampicin (600 mg), and semi-pharmacological dose of atorvastatin, fluvastatin, pitavastatin, and rosuvastatin)
Interventions/Control_2
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	40 years-old >=
Gender	Male
Key inclusion criteria	a) Japanese male subjects at the age of 20-40 at the timing of informed consent b) Person who is judged as an appropriate subject for this clinical study by doctors based on the previous medical history and the results of clinical test at the screening c) BMI of subject should be in the range of 18.5 and 25 at the screening. d) person who can understand and follow the clinical study plan and give us a written informed consent based on the free will
Key exclusion criteria	a) Subjects who have any hypersensitivity to atorvastatin, fluvastatin, pitavasitatin, rosuvastatin, and rifampicin. b) Subjects who is suffering from acute narrow-angle glaucoma. c) Subjects who is suffering from hypotension( systolic blood pressure < 100mmHg ), hypertension (systolic blood pressure > 140mmHg), diabetes and anemia ( Hb < 12.0g/dL ) at the timing of the screening. d) Subjects who donated or lost over 200 mL (1 unit ) of blood in the past 4weeks or over 400mL (2 units) of blood in the past 3months. e) Subjects who suffer/suffered from severe nervous disease, celebrovascular disease, liver disease, kidney disease, endocrine disease, cardiovascular disease, gastrointestinal disease (including disease which is expected to affect the absorption of test drugs), respiratory disease and metabolic disease. f) Subjects who is confirmed to have severe clinical abnormalities judged by the diagnostics or physical examination by chief doctor or associate doctors. g) Subjects who is suffering from clinically severe diseases within 30 days before the administration of test drugs. h) Subjects who take medicine, health foods including St. John's wort, foods or drinks containing greapefruit, orange, and apple, and supplements, and cannot stop taking these during this clinical study. i) Subjects who smoke or take nicotine within 30 days before the administration of test drugs, and cannot stop smoking during this clinical study j) Subjects who take foods/drinks containing alcohol or caffeine one day before the date of hospital admission, and cannot stop taking these until the final day of this study. k) Subjects whose results of alcohol breath test or uninary drug screening are positive at the timing of screening. l) Subjects whose results of any tests of serological reaction for HBs antigen, HCV antibody or HIV antigen and antibody are positive m) Subjects who is not suitable for this study judged by chief doctor or associte doctors.
Target sample size	8

Research contact person
Name of lead principal investigator	Dr. Ken-ichi Furihata
Organization	P-One Clinic,Keikokai Medical Corp.
Division name	Chairman
Address	View Tower Hachioji 4F Yokamachi Hachioji City,Tokyo,Japan 192-0071
TEL	042-625-5216
Email	furihata@p1-clinic.or.jp

Public contact
Name of contact person	Dr. Ken-ichi Furihata
Organization	P-One Clinic,Keikokai Medical Corp.
Division name	Chairman
Address	View Tower Hachioji 4F Yokamachi Hachioji City,Tokyo,Japan 192-0071
TEL	042-625-5216
Homepage URL
Email	furihata@p1-clinic.or.jp

Sponsor
Institute	P-One Clinic,Keikokai Medical Corp.
Institute
Department

Funding Source
Organization	P-One Clinic,Keikokai Medical Corp. Sugiyama Laboratory, RIKEN Innovation Center, Research Cluster for Innovation, RIKEN
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
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

Other administrative information
Date of disclosure of the study information	2017 Year 08 Month 16 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 03 Month 03 Day
Anticipated trial start date	2016 Year 04 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Partially published
URL releasing results
Results
Other related information

Management information
Registered date	2017 Year 08 Month 16 Day
Last modified on	2017 Year 08 Month 16 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032837