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

Study Overview

• Status: Completed
• Conditions: Vertigo; Autonomic Dysfunction
• Intervention / Treatment: Drug: Buspirone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 152040
    • Regional budgetary health care institution "Ivanovo Regional Clinical Hospital"
  • Saint Petersburg, Russian Federation, 191119
    • Limited Liability Company "Research Center Eco-Security"
  • Saint Petersburg, Russian Federation, 194156
    • Limited Liability Company "X7 Clinical Research"
  • Saint Petersburg, Russian Federation, 196143
    • Limited Liability Company "Research Center Eco-Safety"
  • Saint Petersburg, Russian Federation, 197372
    • Limited liability company "MK-Med"
  • Saint Petersburg, Russian Federation, 197706
    • Saint Petersburg State Budgetary Institution of Healthcare "City Hospital No. 40 of Kurortny District"
  • Saint Petersburg, Russian Federation, 198328
    • St. Petersburg State Budgetary Health Institution "City Polyclinic No. 106"
  • Saint Petersburg, Russian Federation, 199178
    • Limited Liability Company "MART"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buspirone, sustained-release tablets, 15 mg; 15 mg/day	Drug: Buspirone; 1 tablet (15 mg) once per day for 28 days
Placebo Comparator: Placebo; 1 placebo tablet/day	Drug: Placebo; 1 placebo tablet once per day for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of response to therapy at Visit 5	A number (%) of patients with reduction of ≥50% in the total Dizziness Handicap Inventory (DHI) score (25-item self-report questionnaire with total score from 0 to 100; higher scores mean a worse outcome) compared to Visit 1	Visit 5 (day 28±1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of response to therapy at Visits 2, 3, and 4.	A number (%) of patients with reduction of ≥50% in the total Dizziness Handicap Inventory (DHI) score (25-item self-report questionnaire with total score from 0 to 100; higher scores mean a worse outcome) compared to Visit 1	Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1)
Total score on the DHI Scale at Visits 2, 3, 4, and 5.	Total Dizziness Handicap Inventory (DHI) score (25-item self-report questionnaire with total score from 0 to 100; higher scores mean a worse outcome)	Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
Change in total DHI score on Visits 2, 3, 4, and 5 compared to Visit 1	The difference between the total Dizziness Handicap Inventory (DHI) score (25-item self-report questionnaire with total score from 0 to 100; higher scores mean a worse outcome) on Visit 2-5 and Visit 1	Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
Proportion of patients with a 30% or greater reduction in DHI score compared to baseline by Visit 2, 3, 4, 5	A number (%) of patients with reduction of ≥30% in the total Dizziness Handicap Inventory (DHI) score (25-item self-report questionnaire with total score from 0 to 100; higher scores mean a worse outcome) compared to Visit 1	Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
Time elapsed before the total DHI score decreased by 50% or more from baseline	Time (days) elapsed before a ≥50% decrease in Dizziness Handicap Inventory (DHI) score (25-item self-report questionnaire with total score from 0 to 100; higher scores mean a worse outcome)	Day 1 - Day 28±1
Time elapsed before the total DHI score decreased by 30% or more from baseline	Time (days) elapsed before a ≥30% decrease in Dizziness Handicap Inventory (DHI) score (25-item self-report questionnaire with total score from 0 to 100; higher scores mean a worse outcome)	Day 1 - Day 28±1
Change in digital rating scale (DRS) score from Visit 1 to Visits 2, 3, 4, 5	The difference between the total DRS score (from minimum of 0 to maximum of 10 points; higher scores mean a worse outcome) on Visit 2-5 and Visit 1	Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
Ddigital rating scale (DRS) score on Visit 2, 3, 4, and 5	DRS score (from minimum of 0 to maximum of 10 points; higher scores mean a worse outcome) on the Visit	Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)
The response on the Likert scale at Visits 2, 3, 4, and 5	Percentage of patients with complete response, significant relief, moderate relief, minor relief, and no response on the Likert scale at Visits 2, 3, 4, and 5.	Visit 2 (day 7±1), Visit 3 (day 14±1), Visit 4 (day 21±1), Visit 5 (day 28±1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability: adverse event (AE) number and frequency	Number and frequency of adverse events (AEs)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: serious AEs (SAEs) number and frequency	Number and frequency of serious AEs (SAEs)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: AE and SAE causal relationship	Number and frequency of AEs and SAEs related to the use of the study drug/placebo	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: Percentage of patients who interrupted treatment due to AE	Number and percentage of patients who interrupted treatment due to AE	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: vital signs - systolic blood pressure (SBP)	SBP, mmHg	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: vital signs - diastolic blood pressure (DBP)	DBP, mmHg	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: vital signs - respiratory rate (RR)	RR, breaths per minute	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: vital signs - heart rate (HR)	HR, beats per minute	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: vital signs - body temperature	Body temperature, centigrade scale	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: physical examination results	Any patient complaints or abnormalities found during examination by a general practitioner	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: results of the neurological examination	Any patient complaints or abnormalities found during examination by a neurologist	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - hemoglobin	Hemoglobin, g/dL	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - hematocrit	Hematocrit, %	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - red blood cells	Red blood cells, 10^6/uL	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - white blood cells	White blood cells, 10^3/uL	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - neutrophils	Neutrophils, %	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - lymphocytes	Lymphocytes, %	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - eosinophils	Eosinophils, %	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - Monocytes	Monocytes, %	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - basophils	Basophils, %	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - platelets	Platelets, 10^3/uL	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: complete blood count - erythrocyte sedimentation rate	Erythrocyte sedimentation rate, mm per hour	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - alanine transaminase (ALT)	ALT in blood serum, U/L	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - aspartate transaminase (AST)	AST in blood serum, U/L	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - total bilirubin	Total bilirubin in blood serum, umol/L	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - glucose	Glucose in blood serum, mmol/L	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - total protein	Total protein in blood serum, g/L	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - creatinine	Creatinine in blood serum, umol/L	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - urea	Urea in blood serum, mmol/L	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: blood test results - prothrombin time	Prothrombin time, s	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: urinalysis - pH	pH of the urine	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: urinalysis - specific gravity	Specific gravity of the urine	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: urinalysis - glucose	Glucose in the urine (mmol/L)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: urinalysis - protein	Protein in the urine (g/L)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: urinalysis (microscopy) - red blood cells	Red blood cells in the urine (number in sight)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: urinalysis (microscopy) - white blood cells	White blood cells in the urine (number in sight)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: heart rate (beats per minute)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: PQ interval (ms)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QRS complex (ms)	From the screening to Visit 6 (day 35±1)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval (QTc)	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QTc (ms)	From the screening to Visit 6 (day 35±1)
Exploratory: total score on the Hamilton scale	Total score on the Hamilton scale (21-item scale with total score from 0 to 52; higher scores mean a worse outcome)	Visit 4 (day 21±1), Visit 5 (day 28±1)
Exploratory: change in total score on the Hamilton scale compared to Visit 1	Difference between the score on the Hamilton scale (21-item scale with total score from 0 to 52; higher scores mean a worse outcome) on Visit 4 or 5 and Visit 1	Visit 4 (day 21±1), Visit 5 (day 28±1)

Collaborators and Investigators

• Sponsor: Valenta Pharm JSC

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Actual): May 9, 2022
• Study Completion (Actual): May 9, 2022

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): June 24, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Vestibular Diseases; Sensation Disorders; Vertigo; Dizziness; Primary Dysautonomias; Autonomic Nervous System Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Anti-Anxiety Agents; Buspirone
• Other Study ID Numbers: BUSP-03-03-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No