UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A three-way crossover clinical pharmacological study to evaluate a drug interaction on P-gp at Blood Brain Barrier between histamine H1 receptor antagonist Ebastine and P-gp inhibitor Verapamil by using saccadic eye movement analyzing system and visual analogue scale (VAS) in healthy Japanese male volunteers
Title of the study (Brief title)	Clinical pharmacological study to evaluate a drug interaction on P-gp at Blood Brain Barrier between histamine H1 receptor antagonist Ebastine and P-gp inhibitor Verapamil
Region	Japan

Condition
Condition	healthy Japanese male volunteers
Classification by specialty	Not applicable
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The aim of this study is to evaluate a drug interaction on P-gp at Blood Brain Barrie in healthy Japanese male volunteers. A three-way crossover with more than a 6-day washout period between study sessions is planed. Three study medication group are as follows; E10 group: oral single dose of Ebastin, histamine H1 receptor antagonist, 10 mg, E20 group: oral single dose of Ebastin 20 mg and EV group: oral single dose of Ebastin 10 mg and oral single dose of Verapamil, P-gp inhibitor, at 3 hours after Ebastin dosing. Sedative side effect of Ebastin is measured with both saccadic eye movement analysis as a subjective evaluation and Visual Analogue Scale (VAS) as an objective evaluation. And PK/PD analysis is also performed.
Basic objectives2	PK,PD
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Not applicable

Assessment
Primary outcomes	Saccadic eye movement peak velocity
Key secondary outcomes	Other saccadic eve movement parameters (latency) Visual analogue scale alertness score Plasma concentration of Carabastine

In outcomes field, the entry of just a few words such as "safety" or "efficiency" will not be accepted. Specify the name of outcome measures, including the time when you plan to measure. Usually, only one primary outcome is accepted. Write the other outcomes in "secondary outcomes" field.

Base
Study type	Interventional

Study design
Basic design	Cross-over
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	No need to know

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Ebastin 10 mg single oral dose
Interventions/Control_2	Ebastin 20 mg single oral dose
Interventions/Control_3	Ebastin 10 mg single oral dose +Verapamil 80 mg single oral dose
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

In interventions field, include the details of interventions, such as duration, amount, and frequency. If the intervention includes prescription or use of medical devices, duration is required.

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	40 years-old >
Gender	Male
Key inclusion criteria	1.Healthy Japanese male volunteer 2.Age from 20<= <40 3.Subjects who can report self condition 4.Without clinically significant abnormalities in a series of screening examination 5.Written informed consent
Key exclusion criteria	1.Any clinically significant history of drug abuse, alcoholic abuse, heart, liver, kidney, lung, and blood disease etc. thought to be not eligible to participate in the study 2.Subjects known to treated with medicine which has a sedative effect or an antihistaminic agents 3.Subjects who can not abstaine from smoking during study period 4. Subjects who have the 1st deg. AV block on their ECG examination at screening visit. 5. Subjects who have any clinically significant abnormalities on their ECG examination at screening visit. 6.Any drug allergy history 7.Subjects who is using excessive alcohol regularly (cannot keep abstinence for study period) 8.Perticipation in any clinical trial within 4 months 9.Donation of more than 200mL blood within 3 months 10.Any use of drugs in the 2 weeks prior to study drug administration 11.Subjects who, in the opinion of the investigator, are not likely to participate in the study for any reason
Target sample size	8

Research contact person
Name of lead principal investigator	Naoki UCHIDA MD.,PhD
Organization	Showa University School of Medicine
Division name	Second department of Pharmacology
Address	1-5-8 Hatanodai Shinagawa-ku Tokyo 142-8555
TEL	03-3784-8128
Email	nuchida@med.showa-u.ac.jp

Public contact
Name of contact person	Naoki UCHIDA MD.,PhD
Organization	Showa University School of Medicine
Division name	Second department of Pharmacology
Address	1-5-8 Hatanodai Shinagawa-ku Tokyo 142-8555
TEL	03-3784-8128
Homepage URL
Email	nuchida@med.showa-u.ac.jp

Sponsor
Institute	Showa University School of Medicine Second department of Pharmacology
Institute
Department

Sponsor means an organization that is responsible for plan, deployment and report of the research including funding management. It doesn't mean funding agency". Therefore, all clinical trial should have the one.

Funding Source
Organization	The Special Subsidies in Subsidies for ordinary expenses of private schools from the Ministry of Education, Culture, Sports, Science and Technology in 2006.
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Yakusen-kai Kannondai Clinic
Name of secondary funｄer(s)	Not applicable

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	2007 Year 02 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2007 Year 01 Month 11 Day
Anticipated trial start date	2007 Year 01 Month 01 Day
Last follow-up date	2007 Year 03 Month 01 Day
Date of closure to data entry	2007 Year 05 Month 01 Day
Date trial data considered complete	2007 Year 05 Month 01 Day
Date analysis concluded	2007 Year 06 Month 01 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results
Results	Cmax and AUC of plasma Carebastine, active metabolite of Ebastine, in E20 were about 2-fold higher than those in E10. The amount of increased of Cmax and AUC was proportionateto dose escalation. The pharmacokinetic profiles of plasma carebastine in EV was similar to those in E10, not co-administered P-gp inhibitor verapamil. That suggested verapamil 80 mg did not affect on ebastine and carebastine PK. No statistically significant change was observed in SPV after dose of ebastine in all E10, E20 and EV groups. And VAS, as a parameter subjective evaluation, was also no significant change in all groups. These results suggested that clinically significant sedative side effect would not occur after dose of the 2nd generation of anti-histamine Ebastine, even though P-gp at BBB was inhibited by verapamil co-administered. Chinese Journal of Pharmacology and Toxicology. 21(4) p.335, 2007 Jpn. J Clin. Pharmacol. Ther., 38(Suppl): S244, 2007
Other related information

Management information
Registered date	2007 Year 01 Month 19 Day
Last modified on	2016 Year 04 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000000691