Clinical trial NCT06843044: Efficacy and Safety of Ranquilon in Patients With Anxiety Disorders Due to Neurasthenia and Adaptation Disorders
Official title: An Open-label, Comparative, Randomized, Multicenter Phase IV Clinical Study to Investigate the Clinical Efficacy and Safety of the Drug Ranquilon, Tablets, 1 mg, in Patients With Anxiety Disorders Due to Neurasthenia and Adaptation Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Anxiety
Neurasthenia
Adaptation Abnormal
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2025-02-24
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study is to evaluate the efficacy of the drug Ranquilon, 1 mg tablets, at a dosage of 6 mg/day compared to the drug Afobazole, 10 mg tablets, at a dosage of 30 mg/day for the treatment of patients with anxiety disorders due to neurasthenia and adaptation disorders.


Eligibility criteria: Inclusion Criteria:

1. Men and women aged 18 to 70 years;
2. Availability of written consent to participate in the study in accordance with current legislation;
3. Patients with anxiety and established diagnoses based on ICD-10 criteria: neurasthenia (F48.0) or adaptation reaction disorder (F43.2);
4. Anxiety severity on the HARS scale of 18-24 points;
5. Assessment of the severity of suicidal thoughts using the Columbia scale \<3 points;
6. Severity of asthenia on the Multidimensional Fatigue Inventory Scale (MFI-20) greater than 50 points;
7. Total score on the Hamilton Depression Rating Scale (HAMD-17) \< 6;
8. Score on the CGI-s scale of at least 4 points;
9. Negative pregnancy test for women with preserved reproductive potential;
10. Agreement to use effective contraceptive methods throughout the study and for 30 days after its completion (for women with preserved reproductive potential and men);
11. Ability to understand the requirements placed on study participants, provide written consent to participate in the study (including for the use and transfer of information regarding the patients' health status relevant to the study), and comply with the procedures outlined in the study protocol.

Non-inclusion Criteria:

1. Known intolerance to the active and/or excipient substances contained in the study drugs;
2. Known lactase deficiency, lactose intolerance, glucose-galactose malabsorption, or galactose intolerance;
3. Patients requiring prohibited concomitant therapy within this study (MAO inhibitors, antidepressants, neuroleptics, anxiolytics and sedatives (including herbal), hypnotics when used on a regular basis), or who have taken these medications within the last month;
4. Established or suspected alcohol/narcotic substance use at the time of screening or randomization, and/or a history of alcohol, narcotic, or drug dependence;
5. Presence of oncological diseases, including in history (except for cured tumors with stable remission for more than 5 years);
6. Presence of tuberculosis, including in history;
7. Presence of HIV, chronic viral hepatitis B/C, syphilis (including in history), or a positive test for HIV, hepatitis B/C, or syphilis during screening;
8. Patients with a diagnosis of other anxiety disorders (F41) established based on ICD-10 criteria;
9. Schizophrenia, schizoaffective disorders, affective disorders, and panic disorders;
10. Acute psychosis (endogenous-processual, organic, or somatogenic), including in history;
11. Organic lesions of the central nervous system of traumatic and alcoholic origin;
12. Post-encephalitic syndrome;
13. Brain tumors, including in history;
14. Degenerative diseases of the central nervous system (CNS), particularly multiple sclerosis;
15. Depressions, including in history;
16. Suicide attempts in history;
17. Generalized anxiety disorder, including in history;
18. Epilepsy, seizures, including in history;
19. Decompensated diabetes mellitus;
20. Established diagnosis of chronic kidney disease stage 3A and above, or estimated glomerular filtration rate (eGFR) calculated by the Cockcroft-Gault formula ≤ 59 ml/min/1.73 m²;
21. Established diagnosis of liver failure of any severity, or elevated levels of ALT, AST or total bilirubin \>3 times the upper limit of normal according to laboratory standards;
22. Conditions following extensive surgical interventions if less than six months have passed since the procedure;
23. Chronic heart failure III-IV functional class according to the New York Heart Association (NYHA) classification;
24. Severe, decompensated, or unstable diseases (any diseases or conditions that threaten the patient's life or worsen the patient's prognosis and make it impossible to conduct clinical research on the patient);
25. Pregnant women, breastfeeding women, or those planning pregnancy during the study and for 30 days after participation ends;
26. Refusal by the patient to use permitted methods of contraception or to completely abstain from sexual contact throughout the entire period of participation in the study starting from Visit 0 and for 30 days after completion of participation;
27. Current participation or planned participation by the patient in psychological or psychotherapeutic activities aimed at treating anxiety disorder during the clinical trial period;
28. Participation in any other clinical trial within 90 days prior to the start of the screening period;
29. Lack of willingness to cooperate from the patient;
30. Other reasons that, in the investigator's opinion, prevent the patient from participating in the study or pose an unjustified risk to the patient.

Exclusion Criteria:

1. The patient's desire to withdraw from the study (withdrawal of informed consent);
2. Each patient has the right to discontinue participation in the study at any time without explanation. Withdrawal from the study will not affect the medical care provided to the patient in the future.
3. The investigator's decision that the patient needs to be excluded in the best interest of the patient;
4. The patient refuses to cooperate with the investigator or is non-compliant;
5. Emergence of reasons/situations during the study that threaten the patient's safety (e.g., hypersensitivity reactions, serious adverse events, etc.);
6. Inclusion of a patient in the study that does not meet the inclusion/exclusion criteria, including cases of deviation from normal values in laboratory test results obtained at Visit 0;
7. Significant violation of the treatment regimen.

   A significant violation is considered:
   1. Missing doses of the study drugs for 2 full consecutive days or more, or
   2. Taking a total number of tablets \< 80% or \> 120% of the full course (the full course for Ranquilon is 168 tablets, and for Afobazole, it is 84 tablets).
8. Positive pregnancy test;
9. Confirmed diagnosis of COVID-19;
10. Emergence of other reasons during the study that prevent its conduct according to the protocol;
11. Patient death;
12. Termination of the study by the Sponsor;
13. Termination of the study by the Investigator;
14. Termination of the study by regulatory authorities.

Primary outcomes:
measure: The proportion of patients with a significant reduction in anxiety levels (by 50% or more) on Hamilton Anxiety Rating Scale (HARS) compared to baseline on Day 29 ± 1 (Visit 3)
timeFrame: Day 29 ± 1 (Visit 3)
Secondary outcomes:
measure: Change in anxiety levels according to the Hamilton Anxiety Rating Scale (HARS) scale on Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Proportion of patients with a reduction in anxiety levels on the Hamilton Anxiety Rating Scale (HARS) scale to 17 points or less on Day 29 ± 1 (Visit 3)
timeFrame: Day 29 ± 1 (Visit 3)
measure: Proportion of patients with a score of 2 points or less on the Clinical Global Impression (CGI-s) scale as assessed by the physician (healthy or borderline disorder) on Day 29 ± 1 (Visit 3)
timeFrame: Day 29 ± 1 (Visit 3)
measure: Change in the severity of the patient's condition on the Clinical Global Impression (CGI-s) scale by Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Change in the total score on the Multidimensional Fatigue Inventory (MFI-20) on Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Proportion of patients with a reduction in total score on the Multidimensional Fatigue Inventory (MFI-20) by 25% on Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Proportion of patients with a reduction in total score on the Multidimensional Fatigue Inventory (MFI-20) by 50% on Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Proportion of patients with a total score on the Multidimensional Fatigue Inventory (MFI-20) reduced to 30 points or less on Day 29 ± 1 (Visit 3)
timeFrame: Day 29 ± 1 (Visit 3)
measure: Absolute value of the patient's self-assessment of their subjective condition for all individual items on the Multidimensional Fatigue Inventory (MFI-20) scale by Day 29 ± 1 (Visit 3)
timeFrame: Day 29 ± 1 (Visit 3)
measure: Change in total score on the Columbia-Suicide Severity Rating Scale (C-SSRS) by Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Change in total score on the Emotional Eating Questionnaire by Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Change in total score on the Psychological Stress Measure (PSM-25) by Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 29 ± 1 (Visit 3)
measure: Safety and Tolerability: adverse event (AE) rate
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 43 ± 1 for each participant
measure: Safety and Tolerability: AEs associated with the study drug
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 43 ± 1 for each participant
measure: Safety and Tolerability: treatment discontinuation
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 43 ± 1 for each participant
measure: Safety and Tolerability: vital signs - systolic blood pressure (SBP)
timeFrame: Screening, day 1, day 29 ± 1, day 43 ± 1
measure: Safety and Tolerability: vital signs - diastolic blood pressure (DBP)
timeFrame: Screening, day 1, day 29 ± 1, day 43 ± 1
measure: Safety and Tolerability: vital signs - respiratory rate (RR)
timeFrame: Screening, day 1, day 29 ± 1, day 43 ± 1
measure: Safety and Tolerability: vital signs - heart rate (HR)
timeFrame: Screening, day 1, day 29 ± 1, day 43 ± 1
measure: Safety and Tolerability: vital signs - body temperature
timeFrame: Screening, day 1, day 29 ± 1, day 43 ± 1
measure: Safety and Tolerability: concomitant treatment
timeFrame: From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to day 43 ± 1 for each participant
measure: Safety and Tolerability: clinical blood test - hemoglobin
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - hematocrit
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - red blood cell count
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - platelet count
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - leukocyte count
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - myelocytes
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - band neutrophils
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - segmented neutrophils
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - basophils
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - monocytes
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: clinical blood test - lymphocytes
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - specific gravity
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - color
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - transparency
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - pH
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - protein
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - glucose
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - red blood cells
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - white blood cells
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - epithelial cells
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - ketone bodies
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: urinalysis - urobilinogen
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - glucose
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - cholesterol
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - protein
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - bilirubin
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - creatinine
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - alkaline phosphatase
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - alanine transaminase
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - aspartate transaminase
timeFrame: Screening, day 29 ± 1
measure: Safety and Tolerability: blood chemistry - urea
timeFrame: Screening, day 29 ± 1
Other outcomes:
Locations:
city: Engels
country: Russian Federation
facility: Engels Psychiatric Hospital State Health Care Institution of the Ministry of Health of the Saratov Region
city: Moscow
country: Russian Federation
facility: Unimed-C Jsc
city: Saint Petersburg
country: Russian Federation
facility: Aurora MedFort LLC
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Research Center Eco-Safety"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Stepmed Clinic"
city: Saratov
country: Russian Federation
facility: Saratov City Psychoneurological Dispensary
Study officials:
References: