Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the rate and extent of absorption of amoxicillin-clavulanic acid 400 mg-57 mg chewable tablets (test) versus Augmentin® (reference) administered as 1 x 400 mg-57 mg chewable tablet under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
400 mg-57 mg chewable tablet
DRUGAugmentin®
400 mg-57 mg chewable tablet
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects will be females and/or males, non-smokers, 18 years of age and older.
Exclusion criteria
Subjects to whom any of the following applies will be excluded from the study: * Clinically significant illnesses within 4 weeks of the administration of study medication. * Clinically significant surgery within 4 weeks prior to the administration of the study medication. * Any clinically significant abnormality found during medical screening. * Any reason which, in the opinion of the medical subinvestigator, would prevent the subject from participating in the study. * Abnormal laboratory tests judged clinically significant. * Positive urine drug screen at screening. * Positive testing for hepatitis B, hepatitis C or HIV at screening. * ECG abnormalities (clinically significant) or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, or diastolic blood pressure lower than 50 or over 90; or heart rate less than 50 bpm) at screening. * Subjects with BMI ≥30.0. * History of significant alcohol abuse within six months of the screening visit or any indication of the regular use of more than two units of alcohol per day (1 Unit = 150 mL of wine or 360 mL of beer or 45 mL of alcohol 40%). * History of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana) within 3 months of the screening visit or hard drugs (such as cocaine, phencyclidine (PCP) and crack) within 1 year of the screening visit. * Any food allergy, intolerance, restriction or special diet that, in the opinion of the medical subinvestigator, contraindicates the subject's participation in this study. * History of allergic or hypersensitivity reactions to amoxicillin or clavulanic acid or other related drugs (e.g. penicillin, cephalosporins, cephamycins). * Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, rifampin/rifabutin; examples of inhibitors: antidepressants, cimetidine, diltiazem, erythromycin, ketoconazole, MAO inhibitors, neuroleptics, verapamil, quinidine, valproic acid) * use of an investigational drug or participation on an investigation study within 30 days prior to the administration of the study medication. * Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug. * Any clinically significant history or presence of clinically significant neurological, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric or metabolic disease. * Any food allergy, intolerance, restriction or special diet that could, in the opinion of the Medical Subinvestigator, contraindicate the subject's participation in this study. * Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products )including natural products, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption. * Subjects who have had a depot injection or an implant of any drug 3 months prior to administration of study medication. * Donation of plasma (500 mL) within 7 days. Donation or loss of whole blood prior to administration of the study medication as follows: * Less than 300 mL of whole blood within 30 days or * 300 mL to 500 mL of whole blood within 45 days or * more than 500 mL of whole blood within 56 days. * Positive alcohol breath test at screening. * Subjects who have used tobacco in any form within the 90 days preceding study drug administration. * Intolerance to venipunctures * Subjects with a clinically significant history of tuberculosis, epilepsy, asthma, diabetes, psychosis, or glaucoma will not be eligible for this study. * Any history of known Augmentin-associated cholestatic jaundice/hepatic dysfunction * Any known active mononucleosis * Subjects with dentures or braces. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration) - Amoxicillin | Blood samples were collected over 10 hour period | Bioequivalence based on Cmax |
| AUC0-inf - [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Amoxicillin | Blood samples were collected over 10 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Amoxicillin | Blood samples were collected over 10 hour period | Bioequivalence based on AUC0-t |
| Cmax (Maximum Observed Concentration) - Clavulanic Acid | Blood samples collected over 10 hour period | Bioequivalence based on Cmax |
| AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Clavulanic Acid | Blood samples collected over 10 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Clavulanic Acid | Blood samples collected over 10 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amoxicillin Clavulanic Acid (Test) First Amoxicillin-Clavulanic Acid 400/57 mg chewable tablet (test) dosed in first period followed by Augmentin® 400/57 mg chewable tablet (reference) dosed in second period | 24 |
| Augmentin® (Reference) First Augmentin® 400/57 mg chewable tablet (reference) dosed in first period followed by Amoxicillin-Clavulanic Acid 400/57 mg chewable tablet (test) dosed in second period | 28 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Difficulty with vein | 1 | 0 |
| Second Intervention | Difficulty with vein | 1 | 0 |
Baseline characteristics
| Characteristic | Amoxicillin Clavulanic Acid (Test) First | Augmentin® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 28 Participants | 52 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 23 Participants | 28 Participants | 51 Participants |
| Region of Enrollment Canada | 24 participants | 28 participants | 52 participants |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 34 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Outcome results
Primary
AUC0-inf - [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Amoxicillin
Bioequivalence based on AUC0-inf
Time frame: Blood samples were collected over 10 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanic Acid | AUC0-inf - [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Amoxicillin | 19089.36 ng*h/mL | Standard Deviation 3440.49 |
| Augmentin® | AUC0-inf - [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Amoxicillin | 19395.97 ng*h/mL | Standard Deviation 3670.87 |
90% CI: [96.71, 100.18]
Primary
AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Clavulanic Acid
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 10 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanic Acid | AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Clavulanic Acid | 2876.99 ng*h/mL | Standard Deviation 1022.59 |
| Augmentin® | AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Clavulanic Acid | 2833.74 ng*h/mL | Standard Deviation 1031.56 |
90% CI: [95.75, 112.5]
Primary
AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Amoxicillin
Bioequivalence based on AUC0-t
Time frame: Blood samples were collected over 10 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanic Acid | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Amoxicillin | 18939.13 ng*h/mL | Standard Deviation 3441.02 |
| Augmentin® | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Amoxicillin | 19263.26 ng*h/mL | Standard Deviation 3640.51 |
90% CI: [96.58, 100.03]
Primary
AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Clavulanic Acid
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 10 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanic Acid | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Clavulanic Acid | 2798.69 ng*h/mL | Standard Deviation 1011.64 |
| Augmentin® | AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Clavulanic Acid | 2749.12 ng*h/mL | Standard Deviation 1018.15 |
90% CI: [95.76, 113.52]
Primary
Cmax (Maximum Observed Concentration) - Amoxicillin
Bioequivalence based on Cmax
Time frame: Blood samples were collected over 10 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanic Acid | Cmax (Maximum Observed Concentration) - Amoxicillin | 7800.48 ng/mL | Standard Deviation 2113.68 |
| Augmentin® | Cmax (Maximum Observed Concentration) - Amoxicillin | 7599.29 ng/mL | Standard Deviation 2222.97 |
90% CI: [98.4, 107.88]
Primary
Cmax (Maximum Observed Concentration) - Clavulanic Acid
Bioequivalence based on Cmax
Time frame: Blood samples collected over 10 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanic Acid | Cmax (Maximum Observed Concentration) - Clavulanic Acid | 1483.32 ng/mL | Standard Deviation 508.73 |
| Augmentin® | Cmax (Maximum Observed Concentration) - Clavulanic Acid | 1449.68 ng/mL | Standard Deviation 497.08 |
90% CI: [95.33, 111.64]