Bioequivalence Study of Clavamox, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml (Pharmtechnology LLC, Belarus), and Augmentin®, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml (GlaxoSmithKline Trading CJSC, Russia), in Healthy Volunteers Under Fasting Conditions

NCT03616301 | Completed Phase 1

• 1 other identifier: FRM-04-AMOX version 2.0
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomized, single-center, single-dose, two-treatment, two-sequence, two-period, crossover, comparative study, where each subject will be 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.

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)

• Number of treatment-related adverse events (AE) for the test and the reference products as assessed by guidance predefined in the protocol

  17 days

• 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

Study Arms (2)

Clavamox, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml

EXPERIMENTAL

Clavamox, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml is the test product. 14 of 28 subjects in each of two cohorts (total number of enrolled volunteers - 56) will be given single oral dose (5 ml containing 400 mg of amoxicillin and 57 mg of clavulanic acid) in period 1 and period 2 of the clinical part of the study.

Drug: Clavamox

Augmentin®, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml

ACTIVE COMPARATOR

Augmentin®, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml is the reference product. 14 of 28 subjects in each of two cohorts (total number of enrolled volunteers - 56) will be given single oral dose (5 ml containing 400 mg of amoxicillin and 57 mg of clavulanic acid) in period 1 and period 2 of the clinical part of the study.

Drug: Augmentin®

Interventions

Clavamox DRUG

Clavamox, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml, manufactured by Pharmtechnology LLC, Belarus

Clavamox, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml

Augmentin® DRUG

Augmentin®, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml, marketed by CJSC GlaxoSmithKline Trading, Russia

Augmentin®, Powder for Oral Suspension, 400 mg + 57 mg / 5 ml

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: This study is an open-label study; 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: July 31, 2018
• First Posted: August 6, 2018
• Study Start: July 28, 2018
• Primary Completion: August 13, 2018
• Study Completion: August 13, 2018
• Last Updated: October 15, 2018

Record last verified: 2018-07

Locations

RU (1)