Bioequivalence Study of Esomeprazole in Healthy Adult Subjects Under Fasting Condition

Study Overview
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Brief Summary
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The current study is conducted to evaluate and compare the relative bioavailability for Esomeprazole in two different products containing 40 mg Esomeprazole after a single oral dose administration under fasting conditions.

Detailed Description
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A randomized, single-dose, two-treatment, partial replicate, three-phase, three-sequence, bioequivalence study of the two study products. Blood samples were collected at different time intervals and stored at -70⁰C freezer. Esomeprazole plasma concentrations were analyzed using a validated LC-MS-MS method then pharmacokinetics and statistical analysis were performed on the concentrations obtained using Phoenix WinNonlin® software.

Official Title
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A Randomized, Single-Dose, Partial Replicate, Three-period, Three-sequence, Open-Label, Bioequivalence Study Comparing Esomeprazole in Two Different Drug Products After Oral Administration to Healthy Adult Subjects Under Fasting Conditions

Conditions
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Bioequivalence

Intervention / Treatment
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* Drug: Test product (T) 40 mg Hard Gelatin Capsules
* Drug: Reference product (R) 40 mg Hard Gelatin Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent is obtained for study. Age 18 - 55 years, Body mass index between 18.5 and 30 kg/m2 Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination. Vital signs without significant deviations. All laboratory screening results are within the normal range or clinically non-significant Exclusion Criteria: History or presence of any disorder or condition that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the investigator. History of any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, allergic, dermatologic, hematologic, neurologic, or psychiatric disease, or cancer. Any confirmed significant allergic reactions against any drug, or multiple allergies. Clinically significant illness 28 days before study period I. Alcohol or any solvent intake. Regular use of medication. Positive urine screening of drugs of abuse. Use of any systemic medications (prescription medications, OTC products, supplements, or herbal preparations) for 14 days prior to dosing and during the study. History or presence of significant smoking (more than one pack per day cigarettes) or refusal to abstain from smoking for 48 hours before dosing until checkout. Blood donation within the past 60 days. Participation in another bioequivalence study within 60 days prior to the start of period I of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A randomized, single-dose, partial replicate crossover, three-phase, three-sequence, two treatments bioequivalence study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test product (T) 40 mg Hard Gelatin Capsules<br>Single oral dose of 40 mg capsule | Drug: Test product (T) 40 mg Hard Gelatin Capsules<br>* Hard Gelatin Capsules products containing 40 mg Esomeprazole<br>|
| Active Comparator: Reference product (R) 40 mg Hard Gelatin Capsules (first dose)<br>Single oral dose of 40 mg capsule | Drug: Reference product (R) 40 mg Hard Gelatin Capsules<br>* Reference product (R) 40 mg Hard Gelatin Capsules<br>|
| Active Comparator: Reference product (R) 40 mg Hard Gelatin Capsules (second dose)<br>Single oral dose of 40 mg capsule | Drug: Reference product (R) 40 mg Hard Gelatin Capsules<br>* Reference product (R) 40 mg Hard Gelatin Capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Cmax is observed as the maximum of Esomeprazole peak concentration | Pre-dose (0) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5 , 6 , 8 , 10 , 12 and 24 hours post dose | 
| Area under the plasma concentration curve from administration to last observed concentration at time t (AUC(0-t)) | The AUC (0-t) is the area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (tlast) | Pre-dose (0) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5 , 6 , 8 , 10 , 12 and 24 hours post dose | 
| Area under the plasma concentration curve extrapolated to infinite time (AUC(0-inf)) | AUC(0-inf) the area under the curve, which is a way of measuring the total amount of the active drug in a subject's system over a period of time from administration (0) to the time that the drug is no longer present in the subject's body (infinity) | Pre-dose (0) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5 , 6 , 8 , 10 , 12 and 24 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum time (Tmax) | Time until Cmax is reached | Pre-dose (0) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5 , 6 , 8 , 10 , 12 and 24 hours post dose | 
| Elimination Rate Constant (Kel) | Kel is a value used in pharmacokinetics to describe the rate at which a drug is removed from the human system | Pre-dose (0) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5 , 6 , 8 , 10 , 12 and 24 hours post dose | 
| Plasma concentration half-life (t1/2) | t1/2 is the time taken for the plasma concentration of a drug to reduce to half its original value. It is used to estimate how long it takes for a drug to be removed from your body. | Pre-dose (0) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, 5, 5.5 , 6 , 8 , 10 , 12 and 24 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esomeprazole, Bioequivalence, Randomized, Replicate