Efficacy and Safety of Buspirone, Sustained-release Tablets, 15 mg in Patients With Autonomic Dysfunction Syndrome Accompanied by Vertigo

Double-blind Placebo-controlled Multicenter Randomized Clinical Trial to Evaluate the Efficacy and Safety of Buspirone, Sustained-release Tablets, 15 mg (JSC Valenta Pharm, Russia) in Patients With Autonomic Dysfunction Syndrome Accompanied by Vertigo

Study to evaluate the efficacy and safety of Buspirone, sustained-release tablets, 15 mg in patients with autonomic dysfunction syndrome accompanied by vertigo

Inclusion Criteria:

1. Signing and dating the patient's Informed Consent Form.
2. Women and men between the ages of 18 and 65, inclusive, at the time of signing the Informed Consent Form.
3. Clinical diagnosis: G90.8 Other autonomic nervous system disorders or G90.9 Autonomic nervous system disorder not specified.
4. Presence of dizziness, total DHI score from 36 to 52 points inclusive.
5. For women of preserved reproductive potential, a negative pregnancy test and agreement to use approved contraceptive methods for the duration of study participation, beginning at visit 0, and for 3 weeks after study termination; for men, agreement to use approved contraceptive methods for the duration of study participation and for 3 weeks after study termination.

Allowed contraceptive methods in this study are: intrauterine device, barrier method, or dual barrier method (condom or occlusion cap (diaphragm or cervical/vaulted cap) plus spermicide). Hormonal contraception is not permitted due to insufficient data on drug interactions of buspirone.

Women with infertility (menopausal (defined as not menstruating for at least 2 years or more) or with documented surgical sterilization (hysterectomy, bilateral oophorectomy, fallopian tubal ligation) and men with documented infertility or vasectomy are also eligible for participation.

Exclusion Criteria:

1. Known or suspected hypersensitivity to the active ingredient or any of the excipients of the study drug/placebo.

2. Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

3. Cumulative score > 2 on the Suicide Risk Assessment Scale.

4. Cumulative score > 16 on the Hamilton Scale.

5. Chronic heart failure New York Heart Association (NYHA) functional class III-IV, angina III-IV.

6. Syncopal and presyncopal conditions, including a history.

7. Acute cardiovascular disease or surgery (myocardial infarction, angioplasty, aortocoronary/mammary coronary artery bypass surgery, unstable angina, etc) less than 6 months before the screening visit.

8. Acute cerebral circulation disorders and/or transient ischemic attacks less than 6 months before the screening visit date.

9. Cardiac rhythm and conduction disorders, including a history. An established artificial pacemaker.

10. Established diagnosis of liver failure, including a history and/or changes in liver enzyme activity:

    • increased aspartate aminotransferase (AST), alanine aminotransferase (ALT) more than 2.5 times the upper limit of normal,
    • increase in the level of total bilirubin more than 1.5 times above the upper limit of normal;
    • Prothrombin time >18 s.

Chronic kidney disease history of stage IIIa-V (as defined by the National Kidney Foundation/Kidney Disease Outcomes Quality Initiative, NKF/KDOQI, 2006).

12. Glomerular filtration rate (GFR) ≤ 60 mL/min, calculated using the CKD-EPI equation, based on serum creatinine levels at screening.

13. Diabetes mellitus of moderate and severe severity, as well as mild subcompensation and decompensation.

14. Myasthenia gravis. 15. Glaucoma. 16. Systemic connective tissue diseases. 17. Autoimmune diseases. 18. The need for surgical and/or endovascular treatment in the next 3 months. 19. Epilepsy or seizures of unclear etiology, including a history of seizures. 20. Alcoholism, drug addiction, substance abuse in the history and/or at the time of screening (alcoholism - use of more than 30 ml of ethyl alcohol per day within the last 6 months; drug addiction - use of any narcotic substances in any dose within the last 6 months; substance abuse - use of any psychoactive substances in any dose within the last 6 months).

21. Schizophrenia, schizoaffective disorder, history of bipolar disorder. 22. Tuberculosis, hepatitis B and C, HIV, syphilis, history or screening results.

23. Conditions after surgical operations, if less than 6 months have passed since the operation.

24. Therapy for cognitive impairment, balance disorders, and dizziness 21 days or less before the date of Visit 1.

25. Use of an irreversible MAO inhibitor within 14 days or a reversible MAO inhibitor within 1 day before Visit 1.

26. Therapy with the following drugs and groups of drugs: 7 days or less before screening:

• Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SSNs);
• Betahistine preparations;
• Cytochrome P450 3A4 (CYP3A4) inhibitors and inducers: erythromycin, itraconazole, nefazodone, diltiazem, verapamil, etc;
• Cimetidine, warfarin, phenytoin, propranolol.

Monoamine oxidase inhibitors (MAOIs):

Do not use MAO inhibitors concomitantly or take the drug earlier than 14 days after withdrawal of an irreversible MAO inhibitor, or less than 1 day after withdrawal of a reversible MAO inhibitor.

27. History of malignancy, except for patients who have not had the disease within the last 5 years, patients with fully cured basal cell carcinoma of the skin, or fully cured carcinoma in situ.

28. Decompensated somatic diseases that, in the opinion of the investigator, would prevent the patient from following the regimen prescribed by the study protocol, or would not allow evaluation of therapy and compliance in accordance with the protocol, or could distort the results of the study.

29. Decompensated neuropsychiatric conditions, including multiple sclerosis, Parkinson's disease, endogenous depression or other conditions that, in the opinion of the investigator, will not permit the patient to follow the regimen prescribed by the research protocol or will not permit an evaluation of treatment effectiveness and compliance in accordance with the protocol, or may skew the results of the study.

30. Women who are pregnant or lactating; women planning to become pregnant within the next 2 months.

31. Patient using or planning to use hormonal contraception during the study 32. Patients who need concomitant therapy prohibited in this study. 33. Participation in another clinical trial within the last 3 months prior to the screening visit date.

34. Acute intoxication caused by alcohol, sleeping pills, analgesics, antipsychotics.

35. Patient's unwillingness or inability to comply with protocol procedures (in the opinion of the study physician).

36. Other conditions that, in the opinion of the Researcher, prevent the patient from being included in the study.

37. Patient is diagnosed with COVID-19 disease at the time of screening; or has symptoms of SARS or COVID-19 within 14 days prior to screening and has a positive rapid test for COVID-19 at screening.

Withdrawal Criteria:

1. Patient's desire to stop participating in the study.
2. Researcher's decision that continued participation in the study is contrary to the patient's best interests.
3. Patient's inclusion in the study in violation of the inclusion and non-inclusion criteria.
4. Researcher's decision to exclude the patient from the study because the patient did not cooperate adequately with the researcher during the study.
5. Skipping 3 or more consecutive study drug/placebo tablets or skipping 6 or more study drug/placebo tablets.
6. Unwanted event requiring withdrawal of study therapy or limiting protocol procedures.
7. Need to prescribe a patient medication from the Prohibited Companion Therapies section.
8. Loss of communication with the patient.
9. Pregnancy of the patient.
10. For each research visit: patient diagnosed with COVID-19 disease at the time of the visit; or presence of symptoms of ARI or COVID-19 within 7 days prior to the research visit and a positive rapid test for COVID-19 at the research visit.