A Bioequivalence Study of Cefadroxil Film Coated Tablets After A Single Oral Dose Administration to Healthy Subjects

Study Overview
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Brief Summary
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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. This study is conducted to determine the bioequivalence of cefadroxil from DURICEF™ film coated tablets manufactured by Smithkline Beecham Egypt, LLC affiliated co. to GalaxoSmithKline (GSK) and cefadroxil from BIODROXIL™ film coated tablets manufactured by Kahira Pharm &amp;Chem .Ind. Co . for Novartis Pharma (NP) after a single oral dose administration of each to healthy adult subjects under fasting conditions. In Period 1, subjects will be randomized to receive cefadroxil tablet manufactured by either GSK or NP. Following a washout of at least 7 days, subjects will be crossed over in Period 2 to receive the cefadroxil tablet that they did not receive in Period 1. DURICEF is a trademark of the GSK group of companies. BIODROXIL is a trademark of Sandoz.

Official Title
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Comparative Randomized, Single Dose, Two-way Crossover, Open-label Study to Determine the Bioequivalence of Cefadroxil From Duricef 1 gm Film Coated Tablets (Smithkline Beecham Egypt, LLC Affiliated Co. to GalaxoSmithKline ) and Biodroxil 1 gm Film Coated Tablets (Kahira Pharm &Chem .Ind. Co. for Novartis Pharma ) After a Single Oral Dose Administration of Each to Healthy Adults Under Fasting Conditions

Conditions
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Infections, Urinary Tract

Intervention / Treatment
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* Drug: Cefadroxil tablets manufactured by GSK
* Drug: Cefadroxil tablets manufactured by NP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female, age 18 to 55 years, inclusive. Body weight within 15 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Subjects will receive a single oral dose of cefadroxil tablet manufactured by GSK under fasting condition in treatment period 1 followed by 7 days washout interval from the first study drug administration. After the washout interval the subjects will receive a single dose of cefadroxil tablet manufactured by NP under fasting condition in treatment period 2 | Drug: Cefadroxil tablets manufactured by GSK<br>* Cefadroxil tablets manufactured by GSK contains 1 mg of Cefadroxil<br>Drug: Cefadroxil tablets manufactured by NP<br>* Cefadroxil tablets manufactured by NP contains 1 mg of Cefadroxil<br>|
| Experimental: Group B<br>Subjects will receive a single oral dose of cefadroxil tablet manufactured by NP under fasting condition in treatment period 1 followed by 7 days washout interval from the first study drug administration. After the washout interval the subjects will receive a single dose of cefadroxil tablet manufactured by GSK under fasting condition in treatment period 2 | Drug: Cefadroxil tablets manufactured by GSK<br>* Cefadroxil tablets manufactured by GSK contains 1 mg of Cefadroxil<br>Drug: Cefadroxil tablets manufactured by NP<br>* Cefadroxil tablets manufactured by NP contains 1 mg of Cefadroxil<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Pre-dose (0.00) and 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose in each treatment period. | 
| 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. Area under the plasma concentration-time curve from time zero (0) to the last measurable concentration (t), as calculated by the linear trapezoidal method. Area under the plasma concentration-time curve from time zero (0) to infinity (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 (Ke), where 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. | Pre-dose (0.00) and 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose in each treatment period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 lambda z, where lambda z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data after each single dose. | Pre-dose (0.00) and 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose in each treatment period. | 
| Apparent First-order Elimination or Terminal Rate Constant (Ke) | 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. | Pre-dose (0.00) and 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose in each treatment period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, film coated tablets, cefadroxil