Amoxicillin-Clavulanic Acid 400 mg-57 mg Chewable Tablets Under Non-Fasting Conditions

Randomized, 2-Way Crossover, Bioequivalence Study of Amoxicillin-Clavulanic Acid 400 mg-57 mg Chewable Tablets and AUGMENTIN® 400 mg-57 mg Chewable Tablets Administered as 1 x 400 mg-57 mg Chewable Tablet in Healthy Subjects Under Fed Conditions

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 fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: amoxicillin-clavulanic acid; Drug: Augmentin®

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3X 2H9
      • Anapharm Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Subjects will be females and/or males, non-smokers, 18 years of age and older.

Exclusion Criteria

• 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 exclusion criteria for female subjects only:

• Breast feeding subjects.
• Positive urine pregnancy test at screening (performed on all females).

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amoxicillin Calvulanic Acid; Amoxicillin Clavulanic Acid 400-57 mg Chewable Tablet (test) dosed in first period followed by Augmentin® 40-57 mg Chewable Tablet (reference) dosed in second period	Drug: amoxicillin-clavulanic acid; 400 mg-57 mg chewable tablet
Active Comparator: Augmentin®; Augmentin® 400-57 mg Chewable Tablet (test) dosed in first period followed by Amoxicillin Clavulanic Acid 400-57 mg Chewable Tablet (reference) dosed in second period	Drug: Augmentin®; 400 mg-57 mg chewable tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (Maximum Observed Concentration) - Amoxicillin	Bioequivalence based on Cmax	Blood samples collected over 10 hour period
AUC0-inf - [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Amoxicillin	Bioequivalence based on AUC0-inf	Blood samples collected over 10 hour period
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	Blood samples collected over 10 hour period
Cmax (Maximum Observed Concentration) - Clavulanic Acid	Bioequivalence based on Cmax	Blood samples were collected over 10 hour period
AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Clavunlanic Acid	Bioequivalence based on AUC0-inf	Blood samples collected over 10 hour period
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	Blood samples collected over 10 hour period

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: Richard Larouche, MD, Anapharm

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): September 1, 2003
• Study Completion (Actual): September 1, 2003

Study Registration Dates

• First Submitted: February 2, 2009
• First Submitted That Met QC Criteria: February 3, 2009
• First Posted (Estimate): February 4, 2009

Study Record Updates

• Last Update Posted (Estimate): August 18, 2009
• Last Update Submitted That Met QC Criteria: July 6, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: 30074 (Registry Identifier: DAIDS-ES Registry Number)