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

• Status: Completed
• Trial end date: 2018-10-08
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Pharmtechnology LLC
• Collaborators: ClinPharmInvest CRO; ClinPharmInvest, LLC
• Treatments: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acid; Clavulanic Acids

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Surgical interventions on the gastrointestinal tract with the exception of appendectomy.

• Acute infectious diseases less than 4 weeks prior to the start of the study.

• ECG abnormalities.

• Sitting systolic blood pressure < 100 mm Hg or > 130 mm Hg and/or sitting diastolic blood pressure < 70 mm Hg or > 90 mm Hg.

• Heart rate <60 or >80 beats per minute at screening check-in.

• Use of liver enzyme inducers and inhibitors, in particular isoenzyme CYP3A4 (inducers:

omeprazole, cimetidine, products containing the extract of Hypericum perforatum, barbiturates, carbamazepine, phenytoin, glucocorticoids; inhibitors: antiviral drugs, clarithromycin, ciprofloxacin, gestodene) within 30 days prior to the start of the study.

• Use of any systemic drugs within 14 days prior to the start of the study.

• Use of OTC drugs, including herbs and nutritional supplements within 7 days prior to the Dosing Date (including vitamins and natural food additives, phyto supplements,herbal preparations such as, cat's claw, angelica officinalis, oenothera, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng).

• Donation of plasma or blood (450 ml or more) within 2 months prior to the start of the study.

• Intake of more than 10 units alcohol per week (1 unit of alcohol is equivalent to ½ liter of beer, 200 ml dry wine or 50 ml of spirits) or history alcoholism, drug addiction, drug abuse.

• Smoking more than 10 cigarettes per day.

• Participation in other clinical trials of medicines within 3 months prior to the start of the study.

• Positive test for syphilis, hepatitis B, hepatitis C or HIV.

• Positive pregnancy test (for female subjects with child bearing potential).

• Breast-feeding.

• Positive test for alcohol.

• Positive urinary screen test for drugs of abuse.

• Oral contraceptives should be withdrawn 2 months prior to the start of the study.

• Subjects who refuse to comply with the study protocol and/or not credible therein and who are, at the discretion of the Principal Investigator, unable to understand and assess the information about the study, expected risks and possible discomfort in the process of signing written informed consent.

• The values of standard laboratory and instrumental parameters that exceed reference values of the local clinical laboratory