A Clinical Pharmacological Study of Rabeprazole Sodium in Japanese Healthy Adult Male Volunteers (Study E3810)

A Clinical Pharmacological Study of Rabeprazole Sodium in Japanese Healthy Adult Male Volunteers

The purpose of this study is to compare the pharmacodynamics/pharmacokinetics of 5 mg, 10 mg, 20 mg and 40 mg of Rabeprazole sodium (E3810) when administered repeatedly once daily for 5 days to healthy adult male Japanese participants. This was a single-center, open-label, randomized, four-treatment, four-way crossover study.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rabeprazole sodium, 5 mg Tablets; Drug: Rabeprazole sodium, 10 mg Tablets; Drug: Rabeprazole sodium, 20 mg Tablets; Drug: Rabeprazole sodium, 40 mg Tablets (two 20 mg Tablets)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Toshima-ku, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy adult Japanese male between the age of 20-40
• body mass index between 18.5-25

Exclusion Criteria:

• clinically significant abnormal physical examination, vital signs or electrocardiogram
• use of any prescription medication, antacid, nutritional supplement, vitamin preparation, or herb-containing drug within the previous 4 weeks
• use of any non-prescription medication within the previous 1 week
• history of drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rabeprazole sodium Tablets, 5 mg	Drug: Rabeprazole sodium, 5 mg Tablets; Rabeprazole sodium Tablets, 5 mg administered for 5 days. Day 1 and Day 5: participants received a single dose with 200 mL of water in the morning while fasting for 10 hours or longer. Day 2 to Day 4: participants received a single dose with 200 mL of water >= 2 hours after the completion of breakfast.; Other Names: E3810, E3810-J081-040
Experimental: Rabeprazole sodium Tablets, 10 mg	Drug: Rabeprazole sodium, 10 mg Tablets; Rabeprazole sodium Tablets, 10 mg administered for 5 days. Day 1 and Day 5: participants received a single dose with 200 mL of water in the morning while fasting for 10 hours or longer. Day 2 to Day 4: participants received a single dose with 200 mL of water >= 2 hours after the completion of breakfast.; Other Names: E3810, E3810-J081-040
Experimental: Rabeprazole sodium Tablets, 20 mg	Drug: Rabeprazole sodium, 20 mg Tablets; Rabeprazole sodium Tablets, 20 mg administered for 5 days. Day 1 and Day 5: participants received a single dose with 200 mL of water in the morning while fasting for 10 hours or longer. Day 2 to Day 4: participants received a single dose with 200 mL of water >= 2 hours after the completion of breakfast.; Other Names: E3810, E3810-J081-040
Experimental: Rabeprazole sodium Tablets, 40 mg (two 20 mg Tablets)	Drug: Rabeprazole sodium, 40 mg Tablets (two 20 mg Tablets); Rabeprazole sodium Tablets, 40 mg (two 20 mg Tablets) administered for 5 days. Day 1 and Day 5: participants received a single dose with 200 mL of water in the morning while fasting for 10 hours or longer. Day 2 to Day 4: participants received a single dose with 200 mL of water, >=2 hours after the completion of breakfast.; Other Names: E3810, E3810-J081-040

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration	The 24-hour intragastric pH monitoring was performed on Day 5 of administration in each study period (Period I-IV). Data was displayed based on the participant's CYP2C19 genotype: CYP2C19-EM are extensive metabolizers who have normal metabolizing capacity. CYP2C19-PM are poor metabolizers with a metabolizing capacity deficiency or remarkably decreased metabolizing capacity.	Day 5 of administration during Period I-IV

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax)	Pharmacokinetic parameter: maximal drug concentration (Cmax) measured in nanograms per milliliter (ng/mL) was calculated on Day 1 and Day 5 of administration during each Period (I-IV). Data was displayed based on the participant's CYP2C19 genotype: CYP2C19-EM are extensive metabolizers who have normal metabolizing capacity. CYP2C19-PM are poor metabolizers with a metabolizing capacity deficiency or remarkably decreased metabolizing capacity.	Day 1 and Day 5 of administration during Period I-IV
Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t])	Pharmacokinetic parameter: Area under the plasma concentration-time curve from time 0 (administration of the drug) to time t (the last quantifiable concentration time point). AUC measured in nanogram hours per milliliter (ng*h/mL) was calculated on Day 1 and Day 5 of administration during each Period (I-IV). Data was displayed based on the participant's CYP2C19 genotype: CYP2C19-EM are extensive metabolizers who have normal metabolizing capacity. CYP2C19-PM are poor metabolizers with a metabolizing capacity deficiency or remarkably decreased metabolizing capacity.	Day 1 and Day 5 of administration during Period I-IV (0, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24 hours post-dose)

Collaborators and Investigators

• Sponsor: Eisai Co., Ltd.
• Investigators: Study Director: Masahiro Munesue, Japan/Asia Clinical Research Product Creation Unit, Japan Clinical Development, Japan Clinical Development Section

Publications and helpful links

General Publications

• Hayato S, Hasegawa S, Hojo S, Okawa H, Abe H, Sugisaki N, Munesue M, Horai Y, Ohnishi A. Dose-response relationships of rabeprazole 5, 10, 20, and 40 mg once daily on suppression of gastric acid secretion through the night in healthy Japanese individuals with different CYP2C19 genotypes. Eur J Clin Pharmacol. 2012 May;68(5):579-88. doi: 10.1007/s00228-011-1164-7. Epub 2011 Nov 23.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: September 14, 2010
• First Submitted That Met QC Criteria: September 14, 2010
• First Posted (Estimate): September 15, 2010

Study Record Updates

• Last Update Posted (Estimate): November 30, 2012
• Last Update Submitted That Met QC Criteria: November 27, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; Rabeprazole; proton pump inhibitor; pharmacodynamics; healthy adult male Japanese subjects
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole
• Other Study ID Numbers: E3810-J081-040

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No