UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	OPEN-LABEL, RANDOMIZED, CROSSOVER STUDY TO ASSESS THE DOSE-DEPENDENT EFFECT OF RIFAMPICIN ON THE PHARMACOKINETICS OF ENDOGENOUS BIOMARKERS AND PROBE DRUGS FOR ASSESSMENT OF DRUG-DRUG INTERACTIONS MEDIATED BY OATP1B
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 OATP1B endogenous substrates, statins (atorvastatin, pitavastatin, rosuvastatin and valsartan) and rifampicin via hepatic OATP1B in Japanese healthy male adults
Basic objectives2	Pharmacokinetics
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Plasma concentrations of coproporphyrins, total and direct bilirubin, bile acids (including glucuronide and sulfate conjugates), and 7a-hydroxy-4-cholesten-3-one, effect of the administration of rifampicin Plasma concentrations of atorvastatin, pitavastatin, rosuvastatin, valsartan and rifampicin, and their metabolites, effect of the coadministration of rifampicin, pharmacokinetic parameters
Key secondary outcomes	Effect of genetic polymorphisms of OATP1B1 and other transporters and metabolizing enzymes related to the disposition of the probe drugs and endogenous substrates

Base
Study type	Interventional

Study design
Basic design	Cross-over
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -but assessor(s) are blinded
Control	Placebo
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	baseline (day0), day 1 Drug administration (semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin) -> (over 1week for washout) -> Drug administration(clinical dose of rifampicin (150 mg), and semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin) -> (over 1week for washout) -> Drug administration(clinical dose of rifampicin (300 mg), and semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin)-> (over 1week for washout) -> Drug administration(clinical dose of rifampicin (600 mg), and semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin)
Interventions/Control_2	baseline (day0), day 1 Drug administration (semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin) -> (over 1week for washout) -> Drug administration(clinical dose of rifampicin (300 mg), and semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin) -> (over 1week for washout) -> Drug administration(clinical dose of rifampicin (150 mg), and semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin)-> (over 1week for washout) -> Drug administration(clinical dose of rifampicin (600 mg), and semi-pharmacological dose of atorvastatin, valsartan, pitavastatin, and rosuvastatin)
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	1.a history of hypersensitivity to atorvastatin, pitavastatin, rosuvastatin, valsartan and rifampicin 2.lactose intolerance 3.hypotension (systolic blood pressure <90 mmHg) or hypertension (systolic blood pressure >160 mmHg) 4.donated or lost 200 mL (1 unit) of blood within 4 weeks before administration of study drugs or 400 mL (2 units) of blood within 3 months before administration of study drugs 5.a medical history/complication of severe nerve disease, cerebrovascular disease, liver disease, kidney disease, endocrine disease, cardiovascular disease, gastrointestinal disease (including digestive system disease which is considered to affect the absorption of study drugs), respiratory disease, metabolic disease, and anemia 6.known to have Gilberts Disease, and/or Rotor syndrome 7.confirmed of a clinically severe abnormality based on medical examination or physical examination by the investigator or subinvestigator 8.a clinically severe disease within 30 days before administration of study drugs 9.took drugs, health food including St. Johns wort, food 14 days prior to dosing and beverages including grapefruit, orange and apple (including food containing them), and nutritional supplements 7 days prior to dosing and cannot comply with prohibition of taking them during the study 10.smoking or taking nicotine within 30 days before administration of study drugs and who cannot comply with smoking cessation during the study period 11.took alcohol/caffeine-containing food on the day before hospitalization in each study period and cannot comply with prohibition of taking them until the day of discharge in each study period 12.tested positive in an alcohol breath test/urine drug test at screening 13.cannot discontinue the use of drugs other than study drugs from 2 weeks before administration of study drugs until the study completion 14.positive to HBs antigens, HCV antibodies, or HIV antigens/antibodies 15.judged inappropriate by the investigator or subinvestigator
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	Hiroyuki Kusuhara
Organization	The University of Tokyo
Division name	Graduate School of Pharmaceutical Sciences
Address	7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
TEL	03-5841-4770
Homepage URL
Email	kusuhara@mol.f.u-tokyo.ac.jp

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

Funding Source
Organization	Pfizer
Organization
Division
Category of Funding Organization	Outside Japan
Nationality of Funding Organization	USA

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	医療法人社団慶幸会　ピーワンクリニック

Other administrative information
Date of disclosure of the study information	2018 Year 08 Month 09 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2018 Year 01 Month 22 Day
Anticipated trial start date	2018 Year 02 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	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2018 Year 08 Month 09 Day
Last modified on	2018 Year 08 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038418