Study of the Safety and Efficacy of Prenofitol Tablets

Stage 1.

Patients meeting all of the following criteria will be eligible for inclusion in the study:

1. Volunteers of either sex, aged 40 to 69 years (inclusive);
2. Provision of signed Informed Consent prior to the initiation of any screening procedures, and, in the Investigator's opinion, the ability to comply with all study requirements;
3. Body mass index (BMI) of 18.5-39.9 kg/m² (inclusive);
4. Low-density lipoprotein cholesterol (LDL-C) level >3 mmol/L and \<6.5 mmol/L at the time of screening;
5. Triglyceride (TG) level \<4.5 mmol/L at the time of screening.
6. Agreement by all volunteers and the female sexual partners of male volunteers of reproductive potential to use barrier methods of contraception throughout the study and for one month after completion of the study;
7. Negative pregnancy test based on a urine test performed at the screening visit (for all female study participants);
8. Negative test results for HIV, hepatitis B and hepatitis C, and syphilis;
9. Negative urine test for narcotic drugs and psychostimulant substances;
10. Negative alcohol test;
11. Ability to attend all study visits. Stage 2

Patients meeting all of the following criteria will be eligible for inclusion in the study:

1. Provision of signed Informed Consent prior to the initiation of any screening procedures, and, in the Investigator's opinion, the ability to comply with all study requirements;
2. Male and female patients aged 40 to 69 years (inclusive);
3. Low-density lipoprotein cholesterol (LDL-C) level >3 mmol/L and \<6.5 mmol/L at the time of screening;
4. Triglyceride (TG) level \<4.5 mmol/L at the time of screening;
5. Essential arterial hypertension;
6. Medically controlled endocrine disorders;
7. Medically controlled diabetes mellitus, with a glycated hemoglobin (HbA1c) level of \<6.5%;
8. Body mass index (BMI) of 18.5-39.9 kg/m² (inclusive);
9. Agreement by all patients and the female sexual partners of male patients of reproductive potential to use barrier methods of contraception throughout the study and for one month after completion of the study.
10. Negative pregnancy test based on a urine test performed at the screening visit (for women of reproductive potential);
11. Negative blood test results for HIV, hepatitis B and hepatitis C, and syphilis;
12. Negative urine test for narcotic drugs and psychostimulant substances;
13. No smoking of tobacco products or use of nicotine-containing products for 6 months prior to screening;
14. Negative cotinine test;
15. Negative alcohol test;
16. Ability to attend all study visits.

Exclusion Criteria:

Stage 1.

1. Inability to read in Russian; inability or unwillingness to understand the nature of the study. Any other conditions that limit the validity of obtaining informed consent or may affect the patient's ability to participate in the study;
2. Significant history of allergic reactions or drug intolerance;
3. Acute coronary syndrome or stroke occurring less than 1 year prior to enrollment in the study;
4. Use of medicinal products that have a pronounced effect on hemodynamics, liver function, or other relevant functions (e.g., barbiturates, omeprazole, cimetidine, rifampicin, etc.) within 2 months prior to the start of the study;
5. Use of medicinal products (prescription or over-the-counter), including herbal medicinal products (e.g., St. John's wort), cytochrome CYP3A enzyme inducers, vitamins, and biologically active food supplements within 14 days prior to the start of the study;
6. Depot injections of any medicinal products within 3 months prior to the start of the study and throughout the entire study period until the patient has completed their participation in the study;
7. Consumption of more than 10 units of alcohol per week (1 unit of alcohol is equivalent to 0.5 L of beer, 200 mL of dry wine, or 50 mL of spirits) or a history of alcoholism;
8. Blood donation of 450 mL or more of blood or plasma within 2 months prior to the study;
9. Clinically significant, in the Investigator's opinion, abnormalities in complete blood count, blood biochemistry, or other laboratory parameters relevant to the safety of participation in the study;
10. Positive test results for HIV, syphilis, or hepatitis B or C markers (HBsAg and anti-HCV);
11. Participation in a clinical trial involving medicinal products within 3 months prior to the start of the study;
12. A history of surgical procedures involving the gastrointestinal tract, except appendectomy;
13. Chronic or acute diseases of the cardiovascular, bronchopulmonary, nervous, or endocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys, or blood; psychiatric disorders, including a history of psychiatric disorders;
14. Acute infectious diseases (influenza, acute respiratory viral infections, etc.) within 4 weeks prior to the start of the study;
15. Dehydration due to diarrhea, vomiting, or any other cause within 24 hours prior to the start of the study;
16. A history of drug and/or medicinal product dependence and/or substance abuse;
17. Positive breath alcohol test or positive urine test for narcotic drugs and/or potent medicinal substances;
18. Positive pregnancy test;
19. Inability to place a venous catheter for blood sampling (e.g., due to skin disorders at venipuncture sites);
20. Mental, physical, or other conditions that prevent the patient from adequately assessing their own behavior and/or properly complying with the requirements of the study protocol;
21. A special diet (e.g., vegetarian, vegan, or sodium-restricted diet) or lifestyle (e.g., night-shift work or extreme physical exertion).

Stage 2.

Patients will not be eligible for inclusion in the study if they meet at least one of the following criteria:

1. Inability to read in Russian; inability or unwillingness to understand the nature of the study. Any other conditions that limit the validity of obtaining informed consent or may affect the patient's ability to participate in the study;
2. Significant history of allergic reactions or drug intolerance;
3. Hypersensitivity to any component of the investigational medicinal products;
4. A history of familial hypercholesterolemia or type I, III, IV, or V hyperlipoproteinemia;
5. Grade III obesity or higher (BMI >40 kg/m²);
6. Use of any statins or regular use of other lipid-lowering medicinal products within 3 months prior to screening;
7. Clinically significant cardiovascular diseases (myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary angioplasty); symptoms of severe congestive heart failure (CHF), functional class (FC) II-IV according to NYHA (or heart failure with preserved ejection fraction [HFpEF] or heart failure with reduced ejection fraction [HFrEF]);
8. Active liver disease at screening; serum transaminase levels more than 3 times the upper limit of normal (ULN) at screening; Child-Pugh class B or C liver cirrhosis; myopathy; serum creatine phosphokinase (CPK) levels more than 4 times the ULN at screening; serum creatinine \<70 μmol/L;
9. Active neoplastic process, carcinoid syndrome, malignancy within 5 years prior to the start of the study, or immunodeficiency disorders;
10. Prior therapy with glucocorticosteroid hormones, systemic antineoplastic agents, or immunosuppressive medicinal products within 6 months prior to screening;
11. Participation in another clinical trial involving a medicinal product concurrently with or within 90 days prior to enrollment in this study;
12. For women of reproductive potential: pregnancy and/or breastfeeding, or refusal to use a reliable method of contraception;
13. Severe, decompensated, or unstable somatic diseases, or any other diseases or conditions that, in the Investigator's opinion, may complicate the interpretation of treatment results;
14. Any hemodynamic type of congestive heart failure (CHF);
15. Requirement for the use of medicinal products prohibited by the study protocol;
16. Unwillingness to participate in the clinical study, or inability or unwillingness of the patient to comply with the treatment protocol requirements, including adherence to the visit schedule and treatment compliance, and to follow the rules of participation in the clinical study.