Mexidol® Efficacy and Safety in Treatment of VCIND in Older Adults

Open-label, Randomized, Comparative, Controlled Study of the Efficacy and Safety of Mexidol® Used as an Add-On to Standard Therapy in Older Adults With Vascular Cognitive Impairment, No Dementia

The primary objective of this study is to evaluate the efficacy of Mexidol® sequential parenteral and oral administration as part of comprehensive therapy in older adults with chronic brain ischemia and vascular cognitive impairment, no dementia (VCIND).

This is a pilot, open-label, prospective, randomized, comparative, controlled study in parallel groups designed to evaluate the efficacy and safety of sequential Mexidol® therapy used in addition to standard therapy in older adults with chronic brain ischemia and vascular cognitive impairment, no dementia (VCIND).

The study included 120 participants randomized into two groups:

• Group 1 received standard therapy combined with Mexidol® solution (500 mg once daily, IV infusion) for the first 5 days, followed by Mexidol® FORTE 250 tablets (250 mg three times daily) for 60 days.
• Group 2 received standard therapy only.

Within each treatment group, a pre-specified subgroup analysis was performed based on the presence or absence of frailty, followed by a comparative analysis of the secondary outcome measures for each subgroup.

Inclusion Criteria:

1. Signed and dated Informed Consent Form (ICF) by the patient or an impartial witness (in case of physical inability to sign)

2. Men and women aged ≥ 75 years at the time of signing the ICF

3. Patients with the diagnosis of mild cognitive disorder / vascular cognitive impairment, no dementia (ICD-10 code F06.7) established at least 1 year prior to screening

4. A total MoCA score of ≤23 points

5. MRI evidence of vascular brain damage obtained within 1 year prior to screening

6. Agreement to use highly effective methods of contraception throughout the study and for 3 weeks after study completion. Eligible participants include:

   • women of childbearing potential, who have a negative pregnancy test and use the following contraceptive methods: a barrier method (condom or occlusive cap [diaphragm or cervical/vault cap]) or a double-barrier method (condom or occlusive cap [diaphragm or cervical/vault cap] plus spermicide [foam/gel/film/cream/suppository]); women of non-childbearing potential with documented history of hysterectomy, tubal ligation, infertility, or postmenopausal status for more than 1 year;
   • fertile men who agree to use barrier contraception; men with documented infertility or prior vasectomy.

Exclusion Criteria:

1. Hypersensitivity to ethylmethylhydroxypyridine succinate or any other components of the investigational product
2. Galactose intolerance, lactase deficiency, or glucose-galactose malabsorption
3. Clinically confirmed dementia, defined with the Mini-Mental State Examination score of ≤ 24 points and/or a diagnosis of dementia established according to the Diagnostic and Statistical Manual of mental disorders, Fifth Edition (DSM-5) criteria
4. Clinical depression, confirmed by a standardized scale score (e.g., Beck Depression Inventory score of ≥ 29 points) or by a psychiatrist's evaluation
5. Chronic heart failure, class III-IV, according to the New York Heart Association (NYHA) Functional Classification at screening
6. Uncontrolled arterial hypertension
7. Uncontrolled diabetes mellitus
8. Thyroid dysfunction: hypothyroidism or hyperthyroidism
9. Impaired renal function (creatinine clearance calculated by the Cockcroft-Gault formula of less than 50 mL/min) at screening
10. Impaired hepatic function (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN) and/or total bilirubin ≥ 1.5 times the ULN) at screening
11. History of Human Immunodeficiency Virus (HIV), syphilis, hepatitis B, and/or hepatitis C
12. Severe vitamin B12 deficiency (less than 150 pmol/L)
13. Acute infectious diseases (influenza, upper respiratory tract infections, or other) within 4 weeks prior to screening
14. Purulent inflammatory diseases of any site
15. Use of prohibited medications or other substances that, in the investigator's opinion, may interfere with the study results within 30 days prior to screening, or the anticipated need for such medications during the patient's participation in the study
16. Use of medications based on ethylmethylhydroxypyridine succinate, trimetazidine, cytoflavin, or meldonium within 2 months prior to study initiation
17. Systemic autoimmune diseases or connective tissue diseases, requiring prior or current treatment with systemic corticosteroids, cytostatics, or other immunosuppressants
18. History of malignant neoplasms except for patients with no evidence of disease for the past 5 years, completely cured basal cell carcinoma of the skin, or completely cured carcinoma in situ
19. Other severe, decompensated, or unstable somatic diseases (any diseases or conditions that are life-threatening, worsen the patient's prognosis, or prevent participation in a clinical trial)
20. Unwillingness or inability of the patient to comply with the Protocol procedures (in the investigator's opinion)
21. History of and/or current alcoholism, drug addiction, or substance abuse at screening
22. History of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychiatric disorders
23. Participation in another clinical trial within 3 months prior to study enrollment
24. Any other conditions that, in the investigator's opinion, preclude the patient's inclusion in the study.