A Bioequivalence Study of Cefadroxil Film Coated Tablets After A Single Oral Dose Administration to Healthy Subjects
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A 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
Cefadroxil tablets manufactured by GSK contains 1 mg of Cefadroxil
Drug: Cefadroxil tablets manufactured by NP
Cefadroxil tablets manufactured by NP contains 1 mg of Cefadroxil
|
| Experimental: Group B 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
Cefadroxil tablets manufactured by GSK contains 1 mg of Cefadroxil
Drug: Cefadroxil tablets manufactured by NP
Cefadroxil tablets manufactured by NP contains 1 mg of Cefadroxil
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Cairo | Egypt |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 201529
Study Results
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 Detail | 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. |
| Arm/Group Title | Treatment A-cefadroxil 1 gm + Treatment B-cefadroxil 1 gm |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 24 |
| COMPLETED | 24 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment A-cefadroxil 1 gm + Treatment B-cefadroxil 1 gm |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 24 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
26.46
(7.68)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
24
100%
|
| Race/Ethnicity, Customized (Number) [Number] | |
| Oriental |
24
100%
|
Outcome Measures
| Title | Maximal Measured Plasma Concentration (Cmax) After a Single Dose |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm |
|---|---|---|
| Arm/Group Description | In each period of the study, participants received one tablet of treatment A (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 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. | In each period of the study, participants received one tablet of 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 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. |
| Measure Participants | 24 | 24 |
| Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter] |
28.18
(8.12)
|
29.20
(8.80)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment A-cefadroxil 1 gm, Treatment B-cefadroxil 1 gm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence is established when 90% Confidence Interval falls within 80-125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Point estimate percent |
| Estimated Value | 95.91 | |
| Confidence Interval |
(2-Sided) 90% 85.67 to 107.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subject population. All participants were present at the time of measurement. |
| Arm/Group Title | Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm |
|---|---|---|
| Arm/Group Description | In each period of the study, participants received one tablet of treatment A (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 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. | In each period of the study, participants received one tablet of 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 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. |
| Measure Participants | 24 | 24 |
| AUC(0-t) |
106.55
(28.64)
|
102.21
(26.06)
|
| AUC(0-infinity) |
111.71
(30.15)
|
106.08
(26.40)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment A-cefadroxil 1 gm, Treatment B-cefadroxil 1 gm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence is established when 90% Confidence Interval falls within 80-125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Point estimate percent |
| Estimated Value | 102.31 | |
| Confidence Interval |
(2-Sided) 90% 90.46 to 115.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Comparison of AUC (0-t) between Treatment A and Treatment B | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Treatment A-cefadroxil 1 gm, Treatment B-cefadroxil 1 gm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence is established when 90% Confidence Interval falls within 80-125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Point estimate percent |
| Estimated Value | 103.13 | |
| Confidence Interval |
(2-Sided) 90% 91.19 to 116.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Comparison of AUC(0-infinity) between Treatment A and Treatment B | |
| Title | Time of the Maximum Plasma Concentration (T-max) and Terminal Half- Life (T-half) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subject population. All participants were present at the time of measurement. |
| Arm/Group Title | Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm |
|---|---|---|
| Arm/Group Description | In each period of the study, participants received one tablet of treatment A (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 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. | In each period of the study, participants received one tablet of 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 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. |
| Measure Participants | 24 | 24 |
| T-max |
1.50
|
1.50
|
| T-half |
2.28
|
2.10
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment A-cefadroxil 1 gm, Treatment B-cefadroxil 1 gm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2670 |
| Comments | ||
| Method | Wilcoxon's Signed-Rank Test | |
| Comments | Comparison of T-max between Treatment A and Treatment B. | |
| Title | Apparent First-order Elimination or Terminal Rate Constant (Ke) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subject population. All participants were present at the time of measurement. |
| Arm/Group Title | Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm |
|---|---|---|
| Arm/Group Description | In each period of the study, participants received one tablet of treatment A (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 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. | In each period of the study, participants received one tablet of 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 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. |
| Measure Participants | 24 | 24 |
| Mean (Standard Deviation) [Per hour] |
0.30
(0.03)
|
0.33
(0.05)
|
Adverse Events
| Time Frame | Adverse events (AE) and serious adverse events (SAE) were reported through out the study (up to 11 days) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | An AE and SAE were reported in all subject population. | |||
| Arm/Group Title | Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm | ||
| Arm/Group Description | In each period of the study, participants received one tablet of treatment A (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 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. | In each period of the study, participants received one tablet of 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 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. | ||
All Cause Mortality |
||||
| Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/24 (0%) | 0/24 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Treatment A-cefadroxil 1 gm | Treatment B-cefadroxil 1 gm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/24 (0%) | 0/24 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
- 201529