Gastrointestinal Diseases
Conditions
Keywords
Bioequivalence, Fed condition, PARIET 20 mg, IDIAZOLE 20mg, Rabeprazole
Brief summary
This is an open-label, randomized, single dose, two-sequence, two-periods crossover study, separated by 7 days washout interval from the first Study Drug Administration. This study is conducted to determine the bioequivalence of Rabeprazole from IDIAZOLE 20mg Delayed-Release (DR) tablets (tabs) and PARIET 20 mg DR tabs after a single oral dose administration of each to healthy adults fed under conditions. In Period 1, subjects will be randomized to either Idiazole 20mg DR tabs or PARIET 20 mg DR tabs. Following a washout of at least 7 days, subjects will be crossed over in Period 2 to receive the treatment that they did not receive in Period 1. PARIET is a registered trademark of EISAI Co. Limited.
Interventions
IDIAZOLE 20mg DR tabs is a delayed-release, enteric-coated tablets containing 20 mg of rabeprazole sodium.
PARIET 20 mg DR tabs is a delayed-release, enteric-coated tablets containing 20 mg rabeprazole sodium.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female, age 18 to 55 years, inclusive. * Body weight within 10 percent of normal range according to the accepted normal values for body mass index (BMI). * Medical demographics without evidence of clinically significant deviation from normal medical condition. * Results of clinical laboratory test are within the normal range or with a deviation that is not considered clinically significant by principal investigator. * Subject does not have allergy to the drugs under investigation.
Exclusion criteria
* Subjects with known allergy to the products tested. * Subjects whose values of BMI were outside the accepted normal ranges. * Female subjects who were pregnant, nursing or taking birth control pills. * Medical demographics with evidence of clinically significant deviation from normal medical condition. * Results of laboratory tests which are clinically significant. * Acute infection within one week preceding first study drug administration. * History of drug or alcohol abuse. * Subject does not agree not to take any prescription or non-prescription drugs within two weeks before first study drug administration and until the end of the study. * Subject is on a special diet (for example subject is vegetarian). * Subject does not agree not to consume any beverages or foods containing methyl-xanthenes e.g. caffeine (coffee, tea, cola, chocolate etc.) 48 hours prior to the study administration of either study period until donating the last sample in each respective period. * Subject does not agree not to consume any beverages or foods containing grapefruit 7 days prior to first study drug administration until the end of the study. * Subject has a history of severe diseases which have direct impact on the study. * Participation in a bioequivalence study or in a clinical study within the last 6 weeks before first study drug administration. * Subject intends to be hospitalized within 6 weeks after first study drug administration. * Subjects who, through completion of this study, would have donated more than 500 milliliter (mL) of blood in 7 days, or 750 mL of blood in 30 days, 1000 mL in 90 days, 1250 mL in 120 days, 1500 ml in 180 days, 2000 mL in 270 days, 2500 mL of blood in 1 year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Measured Plasma Concentration (Cmax) of Rabeprazole | Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2 | Blood samples were collected for pharmacokinetic analyses in each period at specified time points. Pharmacokinetic parameters of rabeprazole were estimated using standard non-compartmental methods. The Cmax was computed directly from measured data. |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC [0-t]) of Rabeprazole | Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2 | Blood samples were collected for pharmacokinetic analyses in each period at specified time points. Pharmacokinetic parameters of rabeprazole were estimated using standard non-compartmental methods. AUC (0-t) was calculated from measured data points from time of administration to time of last quantifiable concentration (Clast) by the linear trapezoidal rule. |
| Mean Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0 to Infinity]) of Rabeprazole | Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2 | Blood samples were collected for pharmacokinetic analyses in each period at specified time points. Pharmacokinetic parameters of rabeprazole were estimated using standard non-compartmental methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time to the Maximum Plasma Concentration (Tmax) of Rabeprazole | Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2 | Blood samples were collected for pharmacokinetic analysis in each period at specified time points. Pharmacokinetic parameters of Rabeprazole were estimated using standard non-compartmental methods. Tmax was computed directly from the measured data. |
| Mean Apparent First-order Elimination or Terminal Rate Constant (Ke) of Rabeprazole | Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2 | Blood samples were collected for pharmacokinetic analysis in each period at specified time points. Pharmacokinetic parameters of Rabeprazole were estimated using standard non-compartmental methods. Ke was derived from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations. |
| Mean Terminal Half Life (t1/2) of Rabeprazole | Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2 | Half life is the period of time required for the concentration or amount of drug in the body to be reduced by one-half. Blood samples were collected for pharmacokinetic analysis in each period at specified time points. Pharmacokinetic parameters of Rabeprazole were estimated using standard non-compartmental methods. t1/2 was calculated as: t1/2 = Ln(2) / (-b), where b was obtained as the slope of the linear regression of the Ln-transformed plasma concentrations versus time in the terminal period of the plasma curve. |
Countries
Egypt
Participant flow
Recruitment details
Bioequivalence of rabeprazole from Idiazole 20 milligram (mg) tablets and Pariet 20 mg tablets was investigated after single oral dose administration to healthy participants under fed conditions. This study was conducted from 22 March 2014 to 30 March 2014.
Pre-assignment details
During this study, 74 participants were screened. One participant was excluded for significant variation in laboratory results at screening and three participants voluntarily withdrew before entering in to period 1. Hence, 70 participants were enrolled and randomized in study, and all 70 participants completed both periods of the study.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Eligible participants received a single oral dose of Pariet 20 mg enteric coated tablets or Idiazole 20 mg gastro-resistant tablets under fed condition in any of the 2 treatment periods. There was a 7 days washout interval between two study drug administration. | 70 |
| Total | 70 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 30.76 Years STANDARD_DEVIATION 9.05 |
| Region of Enrollment Egypt | 70 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 70 |
| other Total, other adverse events | 0 / 70 | 0 / 70 |
| serious Total, serious adverse events | 0 / 70 | 0 / 70 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC [0-t]) of Rabeprazole
Blood samples were collected for pharmacokinetic analyses in each period at specified time points. Pharmacokinetic parameters of rabeprazole were estimated using standard non-compartmental methods. AUC (0-t) was calculated from measured data points from time of administration to time of last quantifiable concentration (Clast) by the linear trapezoidal rule.
Time frame: Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2
Population: All subject population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idiazole 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC [0-t]) of Rabeprazole | 812.30 Hour*nanograms per milliliter | Standard Deviation 461.3 |
| Pariet 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC [0-t]) of Rabeprazole | 843.68 Hour*nanograms per milliliter | Standard Deviation 425.21 |
90% CI: [90.02, 103.44]
Primary
Maximal Measured Plasma Concentration (Cmax) of Rabeprazole
Blood samples were collected for pharmacokinetic analyses in each period at specified time points. Pharmacokinetic parameters of rabeprazole were estimated using standard non-compartmental methods. The Cmax was computed directly from measured data.
Time frame: Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2
Population: All subject population comprised of all participants who received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idiazole 20 mg | Maximal Measured Plasma Concentration (Cmax) of Rabeprazole | 393.50 Nanograms per milliliter | Standard Deviation 158.6 |
| Pariet 20 mg | Maximal Measured Plasma Concentration (Cmax) of Rabeprazole | 415.83 Nanograms per milliliter | Standard Deviation 179.24 |
90% CI: [90.12, 101.65]
Primary
Mean Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0 to Infinity]) of Rabeprazole
Blood samples were collected for pharmacokinetic analyses in each period at specified time points. Pharmacokinetic parameters of rabeprazole were estimated using standard non-compartmental methods.
Time frame: Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2
Population: All subject population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idiazole 20 mg | Mean Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0 to Infinity]) of Rabeprazole | 798.59 Hour*nanograms per milliliter | Standard Deviation 314.16 |
| Pariet 20 mg | Mean Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0 to Infinity]) of Rabeprazole | 931.81 Hour*nanograms per milliliter | Standard Deviation 442.17 |
90% CI: [87.06, 105.17]
Secondary
Mean Apparent First-order Elimination or Terminal Rate Constant (Ke) of Rabeprazole
Blood samples were collected for pharmacokinetic analysis in each period at specified time points. Pharmacokinetic parameters of Rabeprazole were estimated using standard non-compartmental methods. Ke was derived from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations.
Time frame: Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2
Population: All subject population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idiazole 20 mg | Mean Apparent First-order Elimination or Terminal Rate Constant (Ke) of Rabeprazole | 0.21 Per hour | Standard Deviation 0.14 |
| Pariet 20 mg | Mean Apparent First-order Elimination or Terminal Rate Constant (Ke) of Rabeprazole | 0.16 Per hour | Standard Deviation 0.09 |
Secondary
Mean Terminal Half Life (t1/2) of Rabeprazole
Half life is the period of time required for the concentration or amount of drug in the body to be reduced by one-half. Blood samples were collected for pharmacokinetic analysis in each period at specified time points. Pharmacokinetic parameters of Rabeprazole were estimated using standard non-compartmental methods. t1/2 was calculated as: t1/2 = Ln(2) / (-b), where b was obtained as the slope of the linear regression of the Ln-transformed plasma concentrations versus time in the terminal period of the plasma curve.
Time frame: Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2
Population: All subject population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idiazole 20 mg | Mean Terminal Half Life (t1/2) of Rabeprazole | 4.49 Hour | Standard Deviation 2.4 |
| Pariet 20 mg | Mean Terminal Half Life (t1/2) of Rabeprazole | 5.81 Hour | Standard Deviation 3.08 |
Secondary
Mean Time to the Maximum Plasma Concentration (Tmax) of Rabeprazole
Blood samples were collected for pharmacokinetic analysis in each period at specified time points. Pharmacokinetic parameters of Rabeprazole were estimated using standard non-compartmental methods. Tmax was computed directly from the measured data.
Time frame: Pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 14 and 24 hours post-dose in period 1 and 2
Population: All subject population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idiazole 20 mg | Mean Time to the Maximum Plasma Concentration (Tmax) of Rabeprazole | 3.93 Hour | Standard Deviation 1.06 |
| Pariet 20 mg | Mean Time to the Maximum Plasma Concentration (Tmax) of Rabeprazole | 3.86 Hour | Standard Deviation 1 |