Healthy
Conditions
Keywords
Rabeprazole, proton pump inhibitor, pharmacokinetics, pharmacodynamics, healthy adult male Japanese subjects
Brief summary
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.
Interventions
DRUGRabeprazole 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.
DRUGRabeprazole 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.
DRUGRabeprazole 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.
DRUGRabeprazole 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.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | Day 5 of administration during Period I-IV | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1 and Day 5 of administration during Period I-IV | 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. |
| Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | 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) | 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. |
Countries
Japan
Participant flow
Recruitment details
This study was recruited at 1 center in Japan during the period of 14-Sep-2010 to 2-Dec-2010.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population: Group A, Group B, Group C, Group D Includes Group A, Group B, Group C, and Group D. Participants received Rabeprazole sodium Tablets for 5 days in each period.
Group A Period I: 5 mg, Period II: 10 mg, Period III: 20 mg, Period IV: 40 mg
Group B Period I: 10 mg, Period II: 20 mg, Period III: 40 mg, Period IV: 5 mg
Group C Period I: 20 mg, Period II: 40 mg, Period III: 5 mg, Period IV: 10 mg
Group D Period I: 40 mg, Period II: 5 mg, Period III: 10 mg, Period IV: 20 mg
Participants started with a screening period 4 weeks prior to start of administration, followed by study periods I-IV, a washout period consisted of 6 days or longer between each period. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Entire Study Population: Group A, Group B, Group C, Group D |
|---|---|
| Age Continuous | 27.7 years STANDARD_DEVIATION 4.5 |
| Baseline Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours on Day 1 CYP2C19 Extensive Metabolizers 'EM' | 12.57 Percentage of Time in a 24 Hour Period STANDARD_DEVIATION 7.55 |
| Baseline Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours on Day 1 CYP2C19 Poor Metabolizers 'PM' | 9.91 Percentage of Time in a 24 Hour Period STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
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.
Time frame: Day 5 of administration during Period I-IV
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rabeprazole Sodium 5 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Extensive Metabolizers 'EM' (n=16) | 45.63 Percentage of Time in a 24 Hour Period | Standard Deviation 19.17 |
| Rabeprazole Sodium 5 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Poor Metabolizers 'PM' (n=8) | 62.51 Percentage of Time in a 24 Hour Period | Standard Deviation 14.79 |
| Rabeprazole Sodium 10 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Poor Metabolizers 'PM' (n=8) | 71.83 Percentage of Time in a 24 Hour Period | Standard Deviation 14.64 |
| Rabeprazole Sodium 10 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Extensive Metabolizers 'EM' (n=16) | 57.81 Percentage of Time in a 24 Hour Period | Standard Deviation 12.93 |
| Rabeprazole Sodium 20 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Extensive Metabolizers 'EM' (n=16) | 61.36 Percentage of Time in a 24 Hour Period | Standard Deviation 9.72 |
| Rabeprazole Sodium 20 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Poor Metabolizers 'PM' (n=8) | 75.74 Percentage of Time in a 24 Hour Period | Standard Deviation 20.62 |
| Rabeprazole Sodium 40 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Extensive Metabolizers 'EM' (n=16) | 71.52 Percentage of Time in a 24 Hour Period | Standard Deviation 12.2 |
| Rabeprazole Sodium 40 mg Tablet | Percentage Duration With An Intragastric pH >= 4 During The Entire 24 Hours Of Day 5 Administration | CYP2C19 Poor Metabolizers 'PM' (n=8) | 83.08 Percentage of Time in a 24 Hour Period | Standard Deviation 11.13 |
Secondary
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.
Time frame: 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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 215.5 ng*h/mL | Standard Deviation 88.4 |
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 235.7 ng*h/mL | Standard Deviation 97.1 |
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 455.0 ng*h/mL | Standard Deviation 137.7 |
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 584.6 ng*h/mL | Standard Deviation 137.1 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 539.1 ng*h/mL | Standard Deviation 199.6 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 1029.6 ng*h/mL | Standard Deviation 293.9 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 1230.4 ng*h/mL | Standard Deviation 200 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 429.7 ng*h/mL | Standard Deviation 209.4 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 2112.9 ng*h/mL | Standard Deviation 628.8 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 993.7 ng*h/mL | Standard Deviation 476.9 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 2330.6 ng*h/mL | Standard Deviation 662.9 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 866.9 ng*h/mL | Standard Deviation 385.6 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 4627.9 ng*h/mL | Standard Deviation 1296 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 1929.6 ng*h/mL | Standard Deviation 884.1 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 1807.2 ng*h/mL | Standard Deviation 949.2 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC[0-t]) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 4002.3 ng*h/mL | Standard Deviation 1216 |
Secondary
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.
Time frame: Day 1 and Day 5 of administration during Period I-IV
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 137.7 ng/mL | Standard Deviation 55.7 |
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 146.0 ng/mL | Standard Deviation 56.4 |
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 185.1 ng/mL | Standard Deviation 79 |
| Rabeprazole Sodium 5 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 251.9 ng/mL | Standard Deviation 55.1 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 382.8 ng/mL | Standard Deviation 82.9 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 434.7 ng/mL | Standard Deviation 98.5 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 508.5 ng/mL | Standard Deviation 63.8 |
| Rabeprazole Sodium 10 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 253.6 ng/mL | Standard Deviation 120.2 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 891.9 ng/mL | Standard Deviation 210.8 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 654.1 ng/mL | Standard Deviation 348.4 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 821.9 ng/mL | Standard Deviation 231.7 |
| Rabeprazole Sodium 20 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 520.0 ng/mL | Standard Deviation 267.7 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Poor Metabolizers 'PM' (n=8) | 1986.5 ng/mL | Standard Deviation 439.1 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 5: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 1018.5 ng/mL | Standard Deviation 516.9 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Extensive Metabolizers 'EM' (n=16) | 1007.6 ng/mL | Standard Deviation 513.1 |
| Rabeprazole Sodium 40 mg Tablet | Pharmacokinetic Parameter: Maximal Drug Concentration (Cmax) | Day 1: CYP2C19 Poor Metabolizers 'PM' (n=8) | 1574.2 ng/mL | Standard Deviation 596.6 |