Bioequivalence Study of an Amoxicillin-Clavulanic

Bioequivalence Study of an Amoxicillin-Clavulanic Acid Suspension Preparation. Cross-over, Randomized, Single Dose, Two Treatments, Two Periods and Two Sequences Trial in Fasting Conditions

The objective of this study was to confirm if two formulations of amoxicillin and clavulanic acid (suspension) are bioequivalent.

Test product was AUGMENTIN 12H (400 mg Amoxicillin and 57 mg Clavulanic acid/ 5 ml; Glaxo Wellcome France) and reference product AUGMENTIN 12H (400 mg Amoxicillin and 57 mg Clavulanic acid/ 5 ml; GlaxoSmithKline Mexico). The single dosage was 10 ml of suspension.

The study was prospective, open-label, randomized, crossover, single dose, with 02 treatments, 02 sequences and 02 periods, under fasting conditions.

The population was composed of 35 healthy volunteers, both genders, adults between 18-50 years.

The comparative bioavailability of the two formulations was evaluated based in statistical comparisons of relevant pharmacokinetic parameters, obtained from data of drug concentrations in blood.

Study Overview

• Status: Completed
• Conditions: Infections, Respiratory Tract
• Intervention / Treatment: Drug: 400 mg Amoxicillin + 57 mg Clavulanic Acid/ 5 ml; Drug: 400 mg Amoxicillin + 57 mg Clavulanic Acid/ 5 ml

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Both genders. Ages between 18 and 45 years old. BMI (Body Mass Index) between 20 to 26 kg/m2. Anti-doping tests negative results. Females with negative pregnancy tests Clinical biochemical test values: Hematic Biometry, Urine Analysis, Biochemical Profile: (Glucose, Ureic Nitrogen, Urea, Creatinine, Uric Acid, Cholesterol, Triglycerides, Total Proteins, Albumin, Globulin, Bilirubin (total, indirect and direct), Alkaline Phosphatase, Lactic Dehydrogenase, AST, ALT, Calcium, Phosphorus, Sodium, Potassium, Chlorine and Iron), Ac VIH, AgsHB and RPR (luetic test), must fall within an interval between minimum and maximum values in connection to said tests accepted values.

Normal Electrocardiogram and Chest X-rays. In exception cases, accepted may be a candidate for which any previously mentioned test is exceeded regarding considered valid maximum and minimum accepted normal values, as long as it involves an isolated value and there are no other manifestations which could allow assuming that a given value is related to a disease or is remnant of another. These cases must be approved by clinical area and declared as "Non-clinically significant".

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Exclusion Criteria:

Biochemistry, Electrocardiographic Radiological Anomalies; Anti-doping tests positive results, Positive results regarding RPR; VIH and AgsHB tests. Personal or family history of allergy to medication in question. Having any kind of allergy, since these persons are in higher risk of suffering from medicamentous allergy.

Tobacco use. Recreational drug use. Persons undergoing any medical treatment. Existence of concurrent or intercurrent disease. Existence of justified doubt regarding questionnaire answers truthfulness. Having participated in bioequivalence or bioavailability studies or having donated blood 2 months before the study.

Presence of clinically important gastrointestinal diseases or malabsorption history during the last year.

Presence of a medical condition requiring regular medication (with prescription or over-the- counter medication) with systemic absorption.

Narcotics or alcohol addiction history requiring treatment. Finally, excluded will be all those volunteers not meeting that established in Mexican Official Standard NOM-177-SSA1-1998.

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Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A(reference)/B(test); initial administration of reference and cross-over to test	Drug: 400 mg Amoxicillin + 57 mg Clavulanic Acid/ 5 ml; Reference product; Other Names: AUGMENTIN 12H suspension GlaxoSmithKline Mexico; Drug: 400 mg Amoxicillin + 57 mg Clavulanic Acid/ 5 ml; Test product; Other Names: AUGMENTIN 12H suspension GlaxoWellcome Production France
Experimental: B(test)/A(reference); initial administration of test and cross-over to reference	Drug: 400 mg Amoxicillin + 57 mg Clavulanic Acid/ 5 ml; Reference product; Other Names: AUGMENTIN 12H suspension GlaxoSmithKline Mexico; Drug: 400 mg Amoxicillin + 57 mg Clavulanic Acid/ 5 ml; Test product; Other Names: AUGMENTIN 12H suspension GlaxoWellcome Production France

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (CMAX) of Amoxicillin-Clavulanic Acid	Pharmacokinetics	0.0, 0.16, 0.33, 0.66, 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 2.75, 3.0, 3.5, 4.0, 5.0, 6.0, and 8.0 postdosage
Area under the plasma concentration versus time curve (AUC) of Amoxicillin-Clavulanic Acid	Pharmacokinetics	0.0, 0.16, 0.33, 0.66, 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 2.75, 3.0, 3.5, 4.0, 5.0, 6.0, and 8.0 postdosage

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2011
• Primary Completion (Actual): March 30, 2011
• Study Completion (Actual): March 30, 2011

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 17, 2013
• First Posted (Estimate): January 21, 2013

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Bioequivalence; Mexico; Respiratory infections; Amoxicillin-Clavulanic Acid
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections; 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: 116984