Trial Outcomes & Findings for A Bioequivalence Study of Idiazole 20mg DR Tabs and PARIET® 20 mg DR Tabs After a Single Oral Dose Administration Under Fasting Conditions in Healthy Adults (NCT NCT02446483)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

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.

Results posted on

2017-11-17

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Treatment A-rabeprazole 20mg,Then Treatment B-rabeprazole 20mg Participants received one tablet of treatment A (rabeprazole 20 milligram \[mg\] enteric coated tablet) given with 240 milliliter (mL) water according to a plan of randomization. Water was at room temperature and measured with a 250 mL cylinder. After a washout period of 7 days, participants then received one tablet of treatment B (rabeprazole 20 mg gastro-resistant tablet) given with 240 mL water. Participants were admitted the night before study drug administration, supervised for at least 10 hours (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 ante meridiem (am) and 10:51 am on Day 1 of each study period.	Treatment B-rabeprazole 20mg,Then Treatment A-rabeprazole 20mg Participants received one tablet of 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. After a washout period of 7 days, participants then received one tablet of treatment A (rabeprazole 20 mg enteric coated tablet) given with 240 mL water. 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.
Period 1: Intervention Period 1 STARTED	30	30
Period 1: Intervention Period 1 COMPLETED	30	30
Period 1: Intervention Period 1 NOT COMPLETED	0	0
Period 2: Washout Period (7 Days) STARTED	30	30
Period 2: Washout Period (7 Days) COMPLETED	30	30
Period 2: Washout Period (7 Days) NOT COMPLETED	0	0
Period 3: Intervention Period 2 STARTED	30	30
Period 3: Intervention Period 2 COMPLETED	30	30
Period 3: Intervention Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Bioequivalence Study of Idiazole 20mg DR Tabs and PARIET® 20 mg DR Tabs After a Single Oral Dose Administration Under Fasting Conditions in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment A-rabeprazole 20 mg + Treatment B-rabeprazole 20 mg n=60 Participants 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.
Age, Continuous	30.72 Years STANDARD_DEVIATION 9.01 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Region of Enrollment Egypt	60 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Treatment B- Rabeprazole 20 mg n=60 Participants In each period of the study, participants received one tablet of treatment B (rabeprazole 20 mg gastro-resistant tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.	Treatment A- Rabeprazole 20 mg n=60 Participants In each period of the study, participants received one tablet of treatment A (rabeprazole 2 mg enteric coated tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.
Mean Maximal Measured Plasma Concentration (Cmax) After a Single Dose	530.34 Nanogram per mL (ng/mL) Geometric Coefficient of Variation 32.98	543.78 Nanogram per mL (ng/mL) Geometric Coefficient of Variation 35.67

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment B- Rabeprazole 20 mg n=60 Participants In each period of the study, participants received one tablet of treatment B (rabeprazole 20 mg gastro-resistant tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.	Treatment A- Rabeprazole 20 mg n=60 Participants In each period of the study, participants received one tablet of treatment A (rabeprazole 2 mg enteric coated tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.
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	916.07 ng.h/mL Geometric Coefficient of Variation 43.30
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	971.38 ng.h/mL Geometric Coefficient of Variation 41.98

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment B- Rabeprazole 20 mg n=60 Participants In each period of the study, participants received one tablet of treatment B (rabeprazole 20 mg gastro-resistant tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.	Treatment A- Rabeprazole 20 mg n=60 Participants In each period of the study, participants received one tablet of treatment A (rabeprazole 2 mg enteric coated tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.
Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half) Tmax	3.00 h Interval 1.5 to 8.0	2.66 h Interval 1.5 to 5.66
Time of the Maximum Plasma Concentration (T-max) and Terminal Half-life (T-half) T-half	2.50 h Interval 0.7 to 5.73	2.79 h Interval 0.23 to 6.27

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment B- Rabeprazole 20 mg n=57 Participants In each period of the study, participants received one tablet of treatment B (rabeprazole 20 mg gastro-resistant tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.	Treatment A- Rabeprazole 20 mg n=56 Participants In each period of the study, participants received one tablet of treatment A (rabeprazole 2 mg enteric coated tablet) with 240 mL of water either in sequence of treatment AB or treatment BA as per the 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.
Apparent First-order Elimination or Terminal Rate Constant	0.28 Per hour Geometric Coefficient of Variation 46.12	0.35 Per hour Geometric Coefficient of Variation 123.31

Adverse Events

Treatment A- Rabeprazole 20 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment B- Rabeprazole 20 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER