Infections, Urinary Tract
Conditions
Keywords
Bioequivalence, film coated tablets, cefadroxil
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. 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 &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.
Interventions
DRUGCefadroxil tablets manufactured by GSK
Cefadroxil tablets manufactured by GSK contains 1 mg of Cefadroxil
DRUGCefadroxil tablets manufactured by NP
Cefadroxil tablets manufactured by NP contains 1 mg of Cefadroxil
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Measured Plasma Concentration (Cmax) After a 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. | 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. |
| 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 0.25, 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of the Maximum Plasma Concentration (T-max) and Terminal Half- Life (T-half) | Pre-dose (0.00) and 0.25, 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. | 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. |
| Apparent First-order Elimination or Terminal Rate Constant (Ke) | 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. | 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
Total of 24 participants were enrolled in from March-2014 to April-2014. During each study period participants received test (treatment A-cefadroxil tablet) and reference (treatment B-cefadroxil tablet) products.
Pre-assignment details
Total of 28 participants were screened, out of which 4 were screen failure. Of 4 participants, 1 withdrawn due to significant variation in laboratory results and 3 withdrawn upon their will.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A-cefadroxil 1 gm + Treatment B-cefadroxil 1 gm In each period of the study, participants received one tablet of treatment A (cefadroxil 1 gram \[gm\] film coated \[F.C.\] tablet) or treatment B (cefadroxil 1 gm F.C. tablet), given with 240 ml water. Water was at room temperature and measured with a 250 ml cylinder according to a plan of randomization. The study drug administration took place between 09:00 ante meridiem (am) and 09:46 am for both periods in the morning of study Day 1 of each study period. A washout period of 7 days between the two study drug administrations was allowed. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Treatment A-cefadroxil 1 gm + Treatment B-cefadroxil 1 gm |
|---|---|
| Age, Continuous | 26.46 Years STANDARD_DEVIATION 7.68 |
| Race/Ethnicity, Customized Oriental | 24 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
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. 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.
Time frame: 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.
Population: All subject population. All participants were present at the time of measurement.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A-cefadroxil 1 gm | 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) | AUC(0-t) | 106.55 Microgram.hour per milliliter | Geometric Coefficient of Variation 28.64 |
| Treatment A-cefadroxil 1 gm | 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) | AUC(0-infinity) | 111.71 Microgram.hour per milliliter | Geometric Coefficient of Variation 30.15 |
| Treatment B-cefadroxil 1 gm | 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) | AUC(0-t) | 102.21 Microgram.hour per milliliter | Geometric Coefficient of Variation 26.06 |
| Treatment B-cefadroxil 1 gm | 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) | AUC(0-infinity) | 106.08 Microgram.hour per milliliter | Geometric Coefficient of Variation 26.4 |
90% CI: [90.46, 115.7]
90% CI: [91.19, 116.62]
Primary
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.
Time frame: 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.
Population: All subject population: who were crossed over and completed the balance design, were included in the calculation. All participants were present at the time of measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A-cefadroxil 1 gm | Maximal Measured Plasma Concentration (Cmax) After a Single Dose | 28.18 Microgram per milliliter | Geometric Coefficient of Variation 8.12 |
| Treatment B-cefadroxil 1 gm | Maximal Measured Plasma Concentration (Cmax) After a Single Dose | 29.20 Microgram per milliliter | Geometric Coefficient of Variation 8.8 |
90% CI: [85.67, 107.37]
Secondary
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.
Time frame: 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.
Population: All subject population. All participants were present at the time of measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A-cefadroxil 1 gm | Apparent First-order Elimination or Terminal Rate Constant (Ke) | 0.30 Per hour | Standard Deviation 0.03 |
| Treatment B-cefadroxil 1 gm | Apparent First-order Elimination or Terminal Rate Constant (Ke) | 0.33 Per hour | Standard Deviation 0.05 |
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 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.
Time frame: 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.
Population: All subject population. All participants were present at the time of measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A-cefadroxil 1 gm | Time of the Maximum Plasma Concentration (T-max) and Terminal Half- Life (T-half) | T-max | 1.50 Hour |
| Treatment A-cefadroxil 1 gm | Time of the Maximum Plasma Concentration (T-max) and Terminal Half- Life (T-half) | T-half | 2.28 Hour |
| Treatment B-cefadroxil 1 gm | Time of the Maximum Plasma Concentration (T-max) and Terminal Half- Life (T-half) | T-max | 1.50 Hour |
| Treatment B-cefadroxil 1 gm | Time of the Maximum Plasma Concentration (T-max) and Terminal Half- Life (T-half) | T-half | 2.10 Hour |
p-value: 0.267Wilcoxon's Signed-Rank Test