Clinical trial NCT05430217: Efficacy and Safety of Buspirone, Sustained-release Tablets, 15 mg in Patients With Autonomic Dysfunction Syndrome Accompanied by Vertigo
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vertigo
Autonomic Dysfunction
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2022-06-24
Enrollment: 268
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of response to therapy at Visit 5
timeFrame: Visit 5 (day 28±1)
Secondary outcomes:
measure: Frequency of response to therapy at Visits 2, 3, and 4.
timeFrame: Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1)
measure: Total score on the DHI Scale at Visits 2, 3, 4, and 5.
timeFrame: Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
measure: Change in total DHI score on Visits 2, 3, 4, and 5 compared to Visit 1
timeFrame: Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
measure: Proportion of patients with a 30% or greater reduction in DHI score compared to baseline by Visit 2, 3, 4, 5
timeFrame: Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
measure: Time elapsed before the total DHI score decreased by 50% or more from baseline
timeFrame: Day 1 - Day 28±1
measure: Time elapsed before the total DHI score decreased by 30% or more from baseline
timeFrame: Day 1 - Day 28±1
measure: Change in digital rating scale (DRS) score from Visit 1 to Visits 2, 3, 4, 5
timeFrame: Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
measure: Ddigital rating scale (DRS) score on Visit 2, 3, 4, and 5
timeFrame: Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
measure: The response on the Likert scale at Visits 2, 3, 4, and 5
timeFrame: Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
Other outcomes:
measure: Safety and Tolerability: adverse event (AE) number and frequency
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: serious AEs (SAEs) number and frequency
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: AE and SAE causal relationship
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: Percentage of patients who interrupted treatment due to AE
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: vital signs - systolic blood pressure (SBP)
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: vital signs - diastolic blood pressure (DBP)
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: vital signs - respiratory rate (RR)
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: vital signs - heart rate (HR)
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: vital signs - body temperature
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: physical examination results
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: results of the neurological examination
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - hemoglobin
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - hematocrit
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - red blood cells
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - white blood cells
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - neutrophils
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - lymphocytes
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - eosinophils
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - Monocytes
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - basophils
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - platelets
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: complete blood count - erythrocyte sedimentation rate
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - alanine transaminase (ALT)
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - aspartate transaminase (AST)
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - total bilirubin
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - glucose
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - total protein
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - creatinine
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - urea
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: blood test results - prothrombin time
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: urinalysis - pH
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: urinalysis - specific gravity
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: urinalysis - glucose
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: urinalysis - protein
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: urinalysis (microscopy) - red blood cells
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: urinalysis (microscopy) - white blood cells
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval (QTc)
timeFrame: From the screening to Visit 6 (day 35±1)
measure: Exploratory: total score on the Hamilton scale
timeFrame: Visit 4 (day 21±1), Visit 5 (day 28±1)
measure: Exploratory: change in total score on the Hamilton scale compared to Visit 1
timeFrame: Visit 4 (day 21±1), Visit 5 (day 28±1)
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Regional budgetary health care institution "Ivanovo Regional Clinical Hospital"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Research Center Eco-Security"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "X7 Clinical Research"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Research Center Eco-Safety"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "MK-Med"
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Budgetary Institution of Healthcare "City Hospital No. 40 of Kurortny District"
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Health Institution "City Polyclinic No. 106"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "MART"
Study officials:
References: