Gastrointestinal Diseases
Conditions
Keywords
Idiazole 20mg, PARIET 20 mg, Rabeprazole, bioequivalence
Brief summary
This is an open-label, randomized, single dose, two-sequence, two-period crossover study, separated by 7 days washout interval from the first study drug administration. In this study, the bioavailability of Rabeprazole from Idiazole 20 milligram (mg) delayed release (DR) tablets and PARIET 20 mg DR tablets after a single oral dose administration of each to healthy adults under fasting conditions, will be investigated by determining the 90% confidence limits for the log-transformed ratio (Test product / Reference product) for the bioequivalence parameters. The influence of sequence, product and period effect will be tested by analysis of variance (ANOVA). In this study a total of 60 subjects plus 1-4 additional subjects will be enrolled and split into two groups (Group A and B) of 30 each. For each subject, a total of 33 blood draws will be done and the volume of blood will not exceed 300 milliliters (mL) for the study. PARIET is a registered trademark of EISAI Co. Limited.
Interventions
Delayed release tablets containing 20 mg of rabeprazole
Orally administered, delayed-release, enteric-coated tablets containing 20 mg of 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 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 |
|---|---|---|
| Mean Maximal Measured Plasma Concentration (Cmax) After a Single Dose | Pre-dose (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period. | Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as Least Squares Geometric Means with respective Geometric Coefficient of Variation (% CV). |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) and Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-infinity) | Pre-dose (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period. | Plasma samples for PK analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal method. AUC0-infinity was calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, where first-order elimination or terminal rate constant was calculated 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. Values were reported as Least Squares Geometric Means with respective % CV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half) | Pre-dose (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period. | Plasma samples for PK analysis were drawn at indicated time points of each treatment period. If the maximum value occurs at more than one point T-max was defined as the first time point with this value. The elimination or terminal half-life was calculated by dividing 0.693 (natural logarithm of 2) with b obtained as the slope of the linear regression of the logarithmically transformed plasma concentrations versus time in the terminal period of the plasma curve. |
| Apparent First-order Elimination or Terminal Rate Constant | Pre-dose (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period | Plasma samples for PK analysis were drawn at indicated time points of each treatment period. Apparent first-order elimination or terminal rate constant calculated 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. |
Countries
Egypt
Participant flow
Recruitment details
The study was planned on 60 adult healthy male and female participants, aged 18 to 55 years, at a single site of Egypt from 30 January 2014 to 27 October 2014. During each study period participants received test (treatment A- rabeprazole tablet) and reference (treatment B-rabeprazole tablet) products.
Pre-assignment details
Out of 64 participant screened, one participant was excluded because of significant variation in laboratory results and three participant withdrew the consent, remaining 60 were included in period I.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A-rabeprazole 20 mg + Treatment B-rabeprazole 20 mg In each period of the study, participants received one tablet of treatment A (rabeprazole 20 mg enteric coated tablet) or treatment B (rabeprazole 20 mg gastro-resistant tablet), given with 240 mL water according to a plan of randomization. Water was at room temperature and measured with a 250 mL cylinder. Participants were admitted the night before study drug administration, supervised for at least 10 h of overnight fasting, and confined until collecting 12 h blood sample during study drug administration of each period. The study drug administration took place between 10:00 am and 10:51 am on Day 1 of each study period. The two treatment periods were separated by a washout period of 7 days. | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Treatment A-rabeprazole 20 mg + Treatment B-rabeprazole 20 mg |
|---|---|
| Age, Continuous | 30.72 Years STANDARD_DEVIATION 9.01 |
| Region of Enrollment Egypt | 60 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 0 / 60 | 0 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) and Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-infinity)
Plasma samples for PK analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal method. AUC0-infinity was calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, where first-order elimination or terminal rate constant was calculated 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. Values were reported as Least Squares Geometric Means with respective % CV.
Time frame: Pre-dose (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period.
Population: All subject population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A- Rabeprazole 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) and Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-infinity) | AUC0-t | 916.07 ng.h/mL | Geometric Coefficient of Variation 43.3 |
| Treatment A- Rabeprazole 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) and Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-infinity) | AUC0-infinity | 971.38 ng.h/mL | Geometric Coefficient of Variation 41.98 |
| Treatment B- Rabeprazole 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) and Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-infinity) | AUC0-t | 922.52 ng.h/mL | Geometric Coefficient of Variation 40.97 |
| Treatment B- Rabeprazole 20 mg | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) and Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-infinity) | AUC0-infinity | 959.78 ng.h/mL | Geometric Coefficient of Variation 42.21 |
Comparison: Comparison of T- rabeprazole 20 mg and R- rabeprazole 20 mg for AUC0-t.90% CI: [92.54, 105.28]
Comparison: Comparison of Treatment A- rabeprazole 20 mg and Treatment B- rabeprazole 20 mg for AUC0-infinity.90% CI: [91.81, 104.71]
Primary
Mean Maximal Measured Plasma Concentration (Cmax) After a Single Dose
Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as Least Squares Geometric Means with respective Geometric Coefficient of Variation (% CV).
Time frame: Pre-dose (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period.
Population: All subject population comprised of all participants who were crossed over and completed the balance design, were included in the calculation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A- Rabeprazole 20 mg | Mean Maximal Measured Plasma Concentration (Cmax) After a Single Dose | 543.78 Nanogram per mL (ng/mL) | Geometric Coefficient of Variation 35.67 |
| Treatment B- Rabeprazole 20 mg | Mean Maximal Measured Plasma Concentration (Cmax) After a Single Dose | 530.34 Nanogram per mL (ng/mL) | Geometric Coefficient of Variation 32.98 |
90% CI: [95.81, 107.15]
Secondary
Apparent First-order Elimination or Terminal Rate Constant
Plasma samples for PK analysis were drawn at indicated time points of each treatment period. Apparent first-order elimination or terminal rate constant calculated 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 (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period
Population: All subject population. Data is presented for the participants available at the time of assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A- Rabeprazole 20 mg | Apparent First-order Elimination or Terminal Rate Constant | 0.35 Per hour | Geometric Coefficient of Variation 123.31 |
| Treatment B- Rabeprazole 20 mg | Apparent First-order Elimination or Terminal Rate Constant | 0.28 Per hour | Geometric Coefficient of Variation 46.12 |
Secondary
Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half)
Plasma samples for PK analysis were drawn at indicated time points of each treatment period. If the maximum value occurs at more than one point T-max was defined as the first time point with this value. The elimination or terminal half-life was calculated by dividing 0.693 (natural logarithm of 2) with b obtained as the slope of the linear regression of the logarithmically transformed plasma concentrations versus time in the terminal period of the plasma curve.
Time frame: Pre-dose (0.00) and 0.50, 1.00, 1.50, 2.00, 2.33, 2.66, 3.00, 3.33, 3.66, 4.00, 4.33, 4.66, 5.00, 5.33, 5.66, 6.00, 8.00, 12.00 and 14.00 h post-dose in each treatment period.
Population: All Subject Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A- Rabeprazole 20 mg | Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half) | Tmax | 2.66 h |
| Treatment A- Rabeprazole 20 mg | Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half) | T-half | 2.79 h |
| Treatment B- Rabeprazole 20 mg | Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half) | Tmax | 3.00 h |
| Treatment B- Rabeprazole 20 mg | Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half) | T-half | 2.50 h |
p-value: 0.0029Wilcoxon's Signed-Rank Test