Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The purpose of this study is to assess the bioequivalence between Amoxicillin/Clavulanate Potassium Oral Suspension 600/42.9 mg/5 mL and Augmentin ES-600 Oral Suspension, 600/42.9 mg/5 mL in healthy, male and female subjects, under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 600 mg/42.9 mg/5 mL, single-dose fasting
DRUGAugmentin ES-600™
1 x 600 mg/42.9 mg/5 mL, single-dose fasting
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
* Healthy, non-smoking male or non-pregnant, non-lactating female subjects, 18 years of age and over. * Body weight within ±15% of the appropriate weight range published in 1993 by Metropolitan Life Insurance Company, Statistical Bureau and body-mass index (BMI) less than 30. * Negative for: * HIV * Hepatitis B and C * Urine drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone). * Cotinine (urine test) * Breath alcohol (Breathalyzer) * HCG (females only) * No significant diseases or clinically significant abnormal laboratory values. * No clinically significant findings in the physical examination. * No clinically significant findings in vital sign measurements and 12-lead electrocardiogram (ECG). * Informed of the nature of the study and give written consent prior to receiving any study medication. * Female subjects: surgically steril, post-menopausal or practicing a recognized safe method of contraception (abstention, oral or implanted contraceptives, intra-uterine device or consistent condom plus spermicide use).
Exclusion criteria
* Known history or presence of any disease or condition which might compromise the following body systems: immunologic, endocrine, renal, cardiovascular, respiratory, hematologic, gastrointestinal, neurologic, hepatic, psychiatric or dermatologic * More specifically: history or presence of significant: sensitivity to multiple allergens, diarrhea, stomach or intestinal disease, mononucleosis, renal or hepatic dysfunction and asthma. * Known or suspected carcinoma. * Known history or presence of: * Hypersensitivity or idiosyncratic reaction to amoxicillin, clavulanic acid, penicillin, cephalosporins and/or any other β-lactamase inhibitors. * Clavulin-associated jaundice/hepatic dysfunction. * Alcoholism within last 12 months. * Drug dependence and/or substance abuse. * Use of tobacco or nicotine-containing products, within last 12 months. * On a special diet within 4 weeks prior to drug administration (i.e. a deliberate change in diet for any reason). * Participation in another clinical trial or received an investigational product in the previous 30 days prior to drug administration. * Donation up to 250 mK of blood in the previous 30 days, 251-500 mKL in the previous 45 days, 501-750 mL in the previous 60 days or above 750 mL in the previous 90 days prior to study start. * Requirement of any medication, (prescription and/or over-the-counter) or dietary supplements on a routine basis, with the exception of occasional use of acetaminophen and oral or implanted contraceptives. * Difficulty fasting or consuming the standard prescribed meals.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bioequivalence Based on Cmax for Amoxicillin | Blood samples collected over 14 hour period | Cmax - Maximum Observed Concentration |
| Bioequivalence Based on AUC0-inf for Amoxicillin | Blood samples collected over 14 hour period | AUC0-inf - Area under the concentration-time curve from time zero to infinity (extrapolated) |
| Bioequivalence Based on AUC0-t for Amoxicillin | Blood samples collected over 14 hour period | AUC0-t - Area under the concentration-time curve from time zero to time of last non-zero concentration |
| Bioequivalence Based on Cmax for Clavulanic Acid | Blood samples collected over 14 hour period | Cmax - Maximum Observed Concentration |
| Bioequivalence Based on AUC0-inf for Clavulanic Acid | Blood samples collected over 14 hour period | AUC0-inf - Area under the concentration-time curve from zero to infinity (extrapolated) |
| Bioequivalence Based on AUC0-t for Clavulanic Acid | Blood samples collected over 14 hour period | AUC0-t - Area under the concentration-time curve from time zero to time of last non-zero concentration |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test First Amoxicillin and Clavulante Potassium for Oral Suspension, 600/42.9 mg/5mL test product dosed in first period followed by AugmentinES-600™ for Oral Suspension 600/42.9 mg/5mL reference product dosed in second period | 24 |
| Reference First AugmentinES-600™ for Oral Suspension 600/42.9 mg/5mL reference product dosed in first period followed by Amoxicillin and Clavulante Potassium for Oral Suspension 600/42.9 mg/5mL test product dosed in second period | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | Test First | 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 | 24 Participants | 48 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 20 Participants | 18 Participants | 38 Participants |
| Region of Enrollment Canada | 24 participants | 24 participants | 48 participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Outcome results
Primary
Bioequivalence Based on AUC0-inf for Amoxicillin
AUC0-inf - Area under the concentration-time curve from time zero to infinity (extrapolated)
Time frame: Blood samples collected over 14 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanate | Bioequivalence Based on AUC0-inf for Amoxicillin | 27318.54 ng*h/mL | Standard Deviation 4774.49 |
| AugmentinES-600™ | Bioequivalence Based on AUC0-inf for Amoxicillin | 26515.59 ng*h/mL | Standard Deviation 4691.18 |
90% CI: [101.25, 104.88]
Primary
Bioequivalence Based on AUC0-inf for Clavulanic Acid
AUC0-inf - Area under the concentration-time curve from zero to infinity (extrapolated)
Time frame: Blood samples collected over 14 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanate | Bioequivalence Based on AUC0-inf for Clavulanic Acid | 1335.73 ng*h/mL | Standard Deviation 628.13 |
| AugmentinES-600™ | Bioequivalence Based on AUC0-inf for Clavulanic Acid | 1283.73 ng*h/mL | Standard Deviation 508.17 |
90% CI: [94.73, 108.71]
Primary
Bioequivalence Based on AUC0-t for Amoxicillin
AUC0-t - Area under the concentration-time curve from time zero to time of last non-zero concentration
Time frame: Blood samples collected over 14 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanate | Bioequivalence Based on AUC0-t for Amoxicillin | 26662.17 ng*h/mL | Standard Deviation 4754.01 |
| AugmentinES-600™ | Bioequivalence Based on AUC0-t for Amoxicillin | 25906.24 ng*h/mL | Standard Deviation 4662.03 |
90% CI: [101.08, 104.83]
Primary
Bioequivalence Based on AUC0-t for Clavulanic Acid
AUC0-t - Area under the concentration-time curve from time zero to time of last non-zero concentration
Time frame: Blood samples collected over 14 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanate | Bioequivalence Based on AUC0-t for Clavulanic Acid | 1241.09 ng/h/mL | Standard Deviation 627.5 |
| AugmentinES-600™ | Bioequivalence Based on AUC0-t for Clavulanic Acid | 1195.82 ng/h/mL | Standard Deviation 503.91 |
90% CI: [91.95, 109.13]
Primary
Bioequivalence Based on Cmax for Amoxicillin
Cmax - Maximum Observed Concentration
Time frame: Blood samples collected over 14 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanate | Bioequivalence Based on Cmax for Amoxicillin | 7331.46 ng/mL | Standard Deviation 1414.94 |
| AugmentinES-600™ | Bioequivalence Based on Cmax for Amoxicillin | 7235.76 ng/mL | Standard Deviation 1434.42 |
90% CI: [97.71, 105.33]
Primary
Bioequivalence Based on Cmax for Clavulanic Acid
Cmax - Maximum Observed Concentration
Time frame: Blood samples collected over 14 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin Clavulanate | Bioequivalence Based on Cmax for Clavulanic Acid | 516.42 ng/mL | Standard Deviation 197.44 |
| AugmentinES-600™ | Bioequivalence Based on Cmax for Clavulanic Acid | 507.38 ng/mL | Standard Deviation 162.09 |
90% CI: [92.41, 107.52]