Bioequivalence Study of Clavamox, Film-coated Tablets, 875 mg + 125 mg Pharmtechnology LLC, Belarus), and Augmentin®, Film-coated Tablets, 875 mg + 125 mg (GlaxoSmithKline Trading CJSC, Russia), in Healthy Volunteers Under Fasting Conditions

NCT03702894 | Completed Phase 1

• 1 other identifier: № FRM-05-AMOX version 2.0
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This was an open-label, randomized, single-center, single-dose, two-treatment, two-sequence, two-period, crossover, comparative study, where each subject was randomly assigned to the reference or the test formulation in each period of the study (sequences RT or TR), in order to evaluate if both formulations are bioequivalent.The study was conducted in multiple groups.

Conditions

Bioequivalence

Keywords

bioequivalence; amoxicillin; clavulanic acid; Augmentin

Outcome Measures

Primary Outcomes (4)

• Cmax of amoxicillin for the test and the reference products

  Maximum concentration in plasma among observed concentrations at pre-specified time points

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

• AUC0-t of amoxicillin for the test and the reference products

  Area under the plasma concentration versus time curve from time 0 to the last measured concentration

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

• Cmax of clavulanic acid for the test and the reference products

  Maximum concentration in plasma among observed concentrations at pre-specified time points

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

• AUC0-t of clavulanic acid for the test and the reference products

  Area under the plasma concentration versus time curve from time 0 to the last measured concentration

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

Secondary Outcomes (11)

• AUC0-∞ of amoxicillin for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

• AUC0-∞ of clavulanic acid for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

• Tmax of amoxicillin for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

• Tmax of clavulanic acid for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

• T1/2 of amoxicillin for the test and the reference products

  Time points: 0,00 (within 30 minutes before dosing) and 0.25, 0.5, 0.75, 1.00, 1.25, 1.5, 1.75, 2.00, 2.33, 2.67, 3.00, 3.5, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00 hours after dosing

Study Arms (2)

Clavamox,Coated Tablets, 875 mg + 125 mg

EXPERIMENTAL

Clavamox, Film-coated Tablets, 875 mg + 125 mg, is the test product. 14 of 28 subjects in each of two cohorts (total number of enrolled volunteers - 56) were given a single tablet (containing 875 mg mg of amoxicillin and 125 mg of clavulanic acid) in period 1 and period 2 of the clinical part of the study.

Drug: Clavamox

Augmentin®, Coated Tablets, 875 mg + 125 mg

ACTIVE COMPARATOR

Augmentin®, Film-coated Tablets, 875 mg + 125 mg, is the reference product. 14 of 28 subjects in each of two cohorts (total number of enrolled volunteers - 56) were given a single tablet (containing 875 mg mg of amoxicillin and 125 mg of clavulanic acid) in period 1 and period 2 of the clinical part of the study.

Drug: Augmentin®

Interventions

Clavamox DRUG

Clavamox, Film-coated Tablets, 875 mg + 125 mg, manufactured by Pharmtechnology LLC, Belarus

Also known as: the test product

Clavamox,Coated Tablets, 875 mg + 125 mg

Augmentin® DRUG

Augmentin®, Film-coated Tablets, 875 mg + 125 mg, marketed by GlaxoSmithKline Trading CJSC, Russia

Also known as: the reference product

Augmentin®, Coated Tablets, 875 mg + 125 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Caucasian men or women aged between 18 to 45 years
• Subjects having no clinically significant medical history and no clinically significant abnormalities in general physical examination, laboratory assessments and imaging studies.
• Body mass index 18.5-29.9 kg/m² with body mass \>45 kg and ≤100 kg
• Non-breastfeeding women
• Non-pregnant women
• If subject is a female and is of child bearing potential, she should be practicing an acceptable non-hormonal method of birth control for the duration of the study(at least 14 days before the start of the study, throughout the study and 14 days after the completion of the study), such as a combination of male condom and diaphragm with spermicide
• If subject is a male and and has a female partner of child bearing potential, he should be practicing an acceptable method of birth control for the duration of the study(at least 14 days before the start of the study, throughout the study and 14 days after the completion of the study), such as a combination of male condom and spermicide (double barrier method).
• Subjects are able to understand the requirements of the study, to sign a written informed consent, and also to accept all the restrictions imposed during the course of the study, and to agree to return for the required investigations.

You may not qualify if:

• Subjects with a known history of allergic disorders.
• Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients of the test and the reference product.
• Subjects with a known history of drug intolerance.
• History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to any of beta-lactam agents (e.g. a cephalosporin, carbapenem or monobactam).
• History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid.
• Dehydration due to diarrhea, vomiting or other reasons within 24 hours prior to start of the first period of the study.
• Subjects with history of psychiatric disorders.
• History of convulsions, epilepsy and any other neurological disorders.
• Dietary sodium restriction within two weeks prior to start of the study or adherence to special types of diets (vegetarian, vegan, with salt restriction) and lifestyle (work at night, extreme physical activity).
• Use of gestagen-containing injectable hormonal contraceptives, implants, intrauterine hormonal therapeutic systems within 6 months prior to start of the study.
• Female subjects of child bearing potential having unprotected intercourse with an unsterilized sexual partner within 30 days prior to start of the study.
• Consumption of xanthine-containing foods and drinks (tea, coffee, coca-cola, chocolate) within 72 hours prior to start of the first period of the study.
• Consumption of citrus fruits (including grapefruit and grapefruit juice) and cranberries (including cranberry juice and other cranberry drinks) within 14 days prior to start of the study.
• Cardiovascular, respiratory, gastrointestinal diseases, neuroendocrine disorders, renal and/or hepatic impairment, blood system disorders.
• Other conditions which, according to the researcher's judgment, may affect absorption, distribution, biotransformation and elimination of any formulation or increase risks of deterioration of volunteer's condition.

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• ClinPharmInvest, LLC: collaborator

Study Sites (1)

State Autonomous Healthcare Facility of the Yaroslavl Region "Clinical Hospital No. 2"

Yaroslavl, Yaroslavl Oblast, 150010, Russia

Location

MeSH Terms

Interventions

Amoxicillin-Potassium Clavulanate Combination

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Alexander Khokhlov, Professor

  ClinPharmInvest, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The subjects and the investigator will not be blinded towards the identity of the study products. However, analysts will be blinded towards identity of the study products administered.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 11, 2018
• Study Start: September 21, 2018
• Primary Completion: October 8, 2018
• Study Completion: October 8, 2018
• Last Updated: May 14, 2019

Record last verified: 2018-10

Locations

RU (1)