Bioequivalence Study of Perindopril /Amlodipine/Indapamide 8 mg (10 mg)/2.5 mg/10 mg Tablets in Healthy Volunteers Under Fasting Conditions

Inclusion Criteria:

1. Healthy european men or women aged between 18 to 45 years
2. Body mass index 18.5-30 kg/m² according to Quetelet's weight-height index
3. Verified diagnosis "healthy" according to the anamnesis data and the results ofstandard clinical, laboratory and instrumental examination methods, physicalexamination and anamnestic examination
4. The level of systolic blood pressure (SBP) measured in the sitting position at thetime of screening ≥100 mm Hg and ≤ 139 mm Hg and diastolic blood pressure (DBP) ≥ 60mm Hg or ≤ 90 mm Hg; heart rate more than 60 beats/min and less than 90 beats/min atthe time of screening, respiratory rate more than 12 and less than 20 per minute atthe time of screening, body temperature above 35.9 ° C and below 36.9 °C at the timeof screening
5. Subjects are able to understand the requirements of the study
6. Subjects are able to accept all the restrictions imposed during the course of thestudy
7. The written consent of the volunteer to be included in the study
8. For female subject:

• negative pregnancy test;
• adherence to reliable methods of contraception for female of childbearingpotential: sexual continence, or condom + spermicide, or diaphragm + spermicide,started at least 14 days before the first dose of the study drug; intrauterinecontraception is also a reliable method of contraception, installed at least 4weeks before taking the study drugs in the first period;
• сonsent to use these methods of contraception within 30 days after taking thedrug in the second period;
• women who do not use acceptable methods of contraception, if they are consideredincapable of childbearing, will also be able to participate in the study: womenwho have undergone a hysterectomy or tubal ligation, women with a clinicaldiagnosis of infertility, and women who are in menopause (at least a year withoutmenstruation in the absence of alternative pathologies that may cause thecessation of menstruation);
• in case of using contraceptives (injectable and oral hormonal contraceptives,subcutaneous hormonal implants or intrauterine hormonal therapeutic systems), thelatter should be canceled at least 60 days before taking the drug in the firstperiod;

9. For male: consent to use a double barrier method of contraception (condom +spermicide) or complete sexual abstinence, as well as consent not to participate insperm donation during the entire study and 30 days after taking the drug in the secondperiod.

Exclusion Criteria:

1. hypersensitivity to perindopril or any ACE inhibitors, amlodipine, indapamide orexcipients that are part of any of the investigational drugs, or intolerance to thesecomponents;
2. burdened allergic history
3. lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
4. acute infectious diseases or allergic diseases that ended less than 4 weeks beforetaking the drug in the first period;
5. surgical interventions on the gastrointestinal tract, with the exception ofappendectomy
6. clinically significant pathologies of the cardiovascular, bronchopulmonary,neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver,kidneys and blood;
7. the value of standard laboratory and instrumental parameters that go beyond thereference values
8. positive test for syphilis, hepatitis B, hepatitis C or HIV at the time of screening;
9. positive test for alcohol in exhaled air at screening
10. positive urine analysis for the content of narcotic and potent substances duringscreening (opiates, morphine, barbiturates, benzodiazepines, cannabinoids/marijuana)
11. for women - positive pregnancy test at screening
12. adherence to any low-sodium diet within 2 weeks prior to taking the drug in the firststudy period, or adherence to a special diet (vegetarian, vegan, salt-restricted)
13. intake of more than 10 units alcohol per week (1 unit of alcohol is equivalent to 500ml of beer, 200 ml of dry wine or 50 ml of spirits ethyl 40%) or history ofalcoholism, drug addiction, drug abuse;
14. inability to go without food for at least 12 hours and the inability to take the drugon an empty stomach;
15. donation of plasma or blood (450 ml or more) less than 3 months before taking the drugin the first period;
16. the use of injectable and oral hormonal contraceptives for 60 days before taking thedrug in the first period;
17. the use of subcutaneous hormonal implants or intrauterine hormonal therapeutic systemsfor 6 months before taking the drug in the first period;
18. use of any prescription and OTC drugs less than 2 weeks before the screening
19. use of well-known inducers of liver microsomal enzymes (barbiturates, carbamazepine,phenytoin, glucocorticoids, omeprazole, etc.) inhibitors of liver microsomal enzymes (antidepressants, cimetidine, diltiazem, macrolides, imidazoles, neuroleptics,verapamil, fluoroquinolones, antihistamines), vitamins, herbs and food additives (cat's claw, angelica officinalis, oenothera, pyrethrum, garlic, ginger, ginkgo, redclover, horse chestnut, green tea, ginseng; St. john's wort etc.) less than 30 daysbefore enrollement in the study
20. for women: volunteers with preserved reproductive potential who had unprotected sexualintercourse with an unsterilized male partner within 30 days before the first day ofscreening;
21. breastfeeding;
22. participation in other clinical trials of drugs less than 3 months before thescreening;
23. difficulty with taking blood;
24. smoking
25. volunteers who are unwilling or unable to give up alcohol and excessive physicalactivity from the first day of screening until the follow-up visit;
26. consumption of caffeine and xanthine-containing drinks and products (tea, coffee,chocolate, cola, etc.), products containing poppy seeds and use of citrus fruits (including grapefruit and grapefruit juice) from the first day of screening until thefollow-up visit;
27. intense physical activity or following lifestyle (night work, extreme physicalactivity)
28. lack of intention of volunteers to comply with the Protocol requirements throughoutthe course of the study and/or lack, in the opinion of the Investigator, of thevolunteers' ability to understand and evaluate the information on this study as partof the informed consent form signing process, in particular regarding the expectedrisks and possible discomfort;
29. dehydration due to diarrhea, vomiting or other reason within the last 24 hours beforetaking the drug in the first period of the study;
30. the presence of seizures, epilepsy and any other neurological disorders in the historyof volunteers