Efficacy and Safety of Ranquilon in Patients With Anxiety Disorders Due to Neurasthenia and Adjustment Disorders

An Open-label, Comparative, Randomized, Multicenter Phase IV Clinical Study to Evaluate the Clinical Efficacy and Safety of the Drug Ranquilon, Tablets, 1 mg, in Patients With Anxiety Disorders Due to Neurasthenia and Adjustment Disorders

Study is to evaluate the efficacy and safety 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 adjustment disorders.

Study Overview

• Status: Recruiting
• Conditions: Anxiety; Adjustment Disorders; Neurasthenia
• Intervention / Treatment: Drug: Ranquilon; Drug: Afobazole

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Engels, Russian Federation, 413090
    • Recruiting
    • Engels Psychiatric Hospital State Health Care Institution of the Ministry of Health of the Saratov Region
    • Contact: Alexey Kokoshnikov, MD; Phone Number: +7-8453-552633; Email: kokoshnikoff@mail.ru
  • Moscow, Russian Federation, 119571
    • Recruiting
    • Unimed-C Jsc
    • Contact: Elena Volnaya, MD; Phone Number: +7-495-135-50-10; Email: drvolnaya@yandex.ru
  • Saint Petersburg, Russian Federation, 196143
    • Recruiting
    • Limited Liability Company "Research Center Eco-Safety"
    • Contact: Maxim M Gavrik, MD; Phone Number: +7-812-735-96-98; Email: polniy_maximus@mail.ru
  • Saint Petersburg, Russian Federation
    • Recruiting
    • Limited Liability Company "Stepmed Clinic"
    • Contact: Oleg Goncharov, MD, PhD; Phone Number: +7-812-3375800; Email: ovg2804@gmail.com
  • Saint Petersburg, Russian Federation, 194156
    • Recruiting
    • Aurora MedFort LLC
    • Contact: Igor Balaban, MD; Phone Number: +7-921-903-94-95; Email: igorbalaban.81@mail.ru
  • Saratov, Russian Federation, 410038
    • Recruiting
    • Saratov City Psychoneurological Dispensary
    • Contact: Yuriy Filimonov, MD; Phone Number: +7-8452-752797; Email: yuriyfilimonov555@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females aged 18 to 70 years;
2. Written informed consent form in accordance with current legislation;
3. Patients with anxiety and established diagnoses based on ICD-10 criteria: neurasthenia (F48.0) or adjustment 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 of childbearing potential;
10. Agreement to use effective contraceptive methods throughout the study and for 30 days after its completion (for women of childbearing potential and men);
11. Ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of health-related information), 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. Tuberculosis, including in history;
7. Presence of HIV, chronic viral hepatitis B/C, syphilis (including past history), or a positive test for HIV, hepatitis B/C, or syphilis at 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. History of brain tumors (including past diagnoses);
14. Degenerative diseases of the central nervous system (CNS), particularly multiple sclerosis;
15. History of depression (including past episodes);
16. Suicide attempts in history;
17. Generalized anxiety disorder, including in history;
18. History of epilepsy and seizures (including past episodes);
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. History of major surgical interventions within six months prior to screening;
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 poses a life-threatening risk to the patient, worsens the patient's prognosis, or makes participation in the clinical study impossible);
25. Pregnant women, breastfeeding women, or women planning to become pregnant during the study or within 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 patient cooperation;
30. Other reasons, at the investigator's discretion, that may hinder the patient's participation in the study or pose unjustified risk to the patient.

Exclusion Criteria:

1. The patient's decision to withdraw from the study (revocation 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 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. Sponsor-initiated study termination;
13. Termination of the study by the Investigator;
14. Termination of the study by regulatory authorities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ranquilon, 6 mg/day; Ranquilon, 1 mg tablets, at a dosage of 6 mg/day for 28 days	Drug: Ranquilon; 1 mg tablets; Other Names: GB-115; N-(6-phenylhexanoyl)glycyl-L-tryptophan amide
Active Comparator: Afobazole, 30 mg/day; Afobazole, 10 mg tablets, at a dosage of 30 mg/day for 28 days	Drug: Afobazole; 10 mg tablets; Other Names: Fabomotizole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	HARS scale includes 14 items, each of which is rated on the Likken scale (from 0 points as absence of the symptom to 4 points as the worst possible symptom). Of these, 13 items relate to the manifestation of anxiety in daily life, 14th item relate to the manifestation of anxiety during examinations.	Day 29 ± 1 (Visit 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	The scale ranges from 1 to 7 points, where 1 indicates healthy and 7 indicates very severe disorder.	Day 29 ± 1 (Visit 3)
Change in total score on the Columbia-Suicide Severity Rating Scale (C-SSRS) by Day 29 ± 1 (Visit 3) compared to baseline	A severity rating of "3" or higher indicates a serious risk of suicide. A rating of "5" and any identified suicidal actions indicate an extremely high risk and an absolute necessity for urgent therapeutic measures and hospitalization. The section "intensity of suicidal thoughts" allows for a more accurate assessment of severity and prediction of its dynamics.	Day 29 ± 1 (Visit 3)
Change in total score on the Emotional Eating Questionnaire by Day 29 ± 1 (Visit 3) compared to baseline	The scale ranges from 0 to 30 points, where a minimum indicates no emotional overeating and a maximum indicates a strong dependence of eating behavior on emotional state.	Day 29 ± 1 (Visit 3)
Change in total score on the Psychological Stress Measure (PSM-25) by Day 29 ± 1 (Visit 3) compared to baseline	A score below 99 indicates low stress, a score between 100-125 indicates moderate stress; a score above 125 indicates high stress	Day 29 ± 1 (Visit 3)
Safety and Tolerability: adverse event (AE) rate	Number and frequency of adverse events (AEs) or serious AEs (SAEs)	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
Safety and Tolerability: AEs associated with the study drug	Number and frequency of AEs or SAEs associated with the study drug	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
Safety and Tolerability: treatment discontinuation	Percentage of patients who discontinued treatment due to the occurrence of AEs/SAEs	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
Safety and Tolerability: vital signs - systolic blood pressure (SBP)	SBP, mmHg	Screening, day 1, day 29 ± 1, day 43 ± 1
Safety and Tolerability: vital signs - diastolic blood pressure (DBP)	DBP, mmHg	Screening, day 1, day 29 ± 1, day 43 ± 1
Safety and Tolerability: vital signs - respiratory rate (RR)	RR, breaths per minute	Screening, day 1, day 29 ± 1, day 43 ± 1
Safety and Tolerability: vital signs - heart rate (HR)	HR, beats per minute	Screening, day 1, day 29 ± 1, day 43 ± 1
Safety and Tolerability: vital signs - body temperature	Body temperature, Celsius scale	Screening, day 1, day 29 ± 1, day 43 ± 1
Safety and Tolerability: concomitant treatment	Data on concomitant treatment (if any)	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
Safety and Tolerability: clinical blood test - hemoglobin	Hemoglobin (g/L)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - hematocrit	Hematocrit (%)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - red blood cell count	Red blood cell count (cells/L)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - platelet count	Platelet count (cells/L)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - leukocyte count	Leukocyte count (cells/L)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate	Erythrocyte sedimentation rate (mm/h)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - myelocytes	Leukocyte formula (myelocytes, %)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - band neutrophils	Leukocyte formula (band neutrophils, %)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - segmented neutrophils	Leukocyte formula (eosinophils, %)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - basophils	Leukocyte formula (basophils, %)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - monocytes	Leukocyte formula (monocytes, %)	Screening, day 29 ± 1
Safety and Tolerability: clinical blood test - lymphocytes	Leukocyte formula (lymphocytes, %)	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - specific gravity	Specific gravity of the urine	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - color	Color of the urine	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - transparency	Transparency of the urine	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - pH	pH of the urine	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - protein	Protein concentration (g/L)	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - glucose	Glucose concentration (mmol/L)	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - red blood cells	Red blood cell content (number in sight)	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - white blood cells	White blood cell content (number in sight)	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - epithelial cells	Epithelial cell content (number in sight)	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - ketone bodies	Ketone bodies (mmol/L)	Screening, day 29 ± 1
Safety and Tolerability: urinalysis - urobilinogen	Urobilinogen (mcmol/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - glucose	Glucose concentration (mmol/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - cholesterol	Total cholesterol concentration (mmol/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - protein	Total protein concentration (g/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - bilirubin	Total bilirubin concentration (micromol/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - creatinine	Creatinine concentration (micromol/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - alkaline phosphatase	Alkaline phosphatase activity (U/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - alanine transaminase	Alanine transaminase activity (U/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - aspartate transaminase	Aspartate transaminase activity (U/L)	Screening, day 29 ± 1
Safety and Tolerability: blood chemistry - urea	Urea concentration (mmol/L)	Screening, day 29 ± 1
Change in anxiety levels according to the Hamilton Anxiety Rating Scale (HARS) scale on Day 29 ± 1 (Visit 3) compared to baseline	HARS scale includes 14 items, each of which is rated on the Likken scale (from 0 points as absence of the symptom to 4 points as the worst possible symptom). Of these, 13 items relate to the manifestation of anxiety in daily life, 14th item relate to the manifestation of anxiety during examinations.	Day 29 ± 1 (Visit 3)
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)	HARS scale includes 14 items, each of which is rated on the Likken scale (from 0 points as absence of the symptom to 4 points as the worst possible symptom). Of these, 13 items relate to the manifestation of anxiety in daily life, 14th item relate to the manifestation of anxiety during examinations.	Day 29 ± 1 (Visit 3)
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	The scale ranges from 1 to 7 points, where 1 indicates healthy and 7 indicates very severe disorder.	Day 29 ± 1 (Visit 3)
Change in the total score on the Multidimensional Fatigue Inventory (MFI-20) on Day 29 ± 1 (Visit 3) compared to baseline	If the total score on any of the subscales (General Fatigue, Reduced Activity, Decreased Motivation, Physical Fatigue, Mental Fatigue) is above 12, it may serve as preliminary grounds for diagnosing "asthenic syndrome." Each subscale is assessed from 4 points (lack of symptoms) to 20 points (worst symptoms possible).	Day 29 ± 1 (Visit 3)
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	Normally, the total number of points should not exceed 30. If the total score on any of the subscales (General Fatigue, Reduced Activity, Decreased Motivation, Physical Fatigue, Mental Fatigue) is above 12, it may serve as preliminary grounds for diagnosing "asthenic syndrome." Each subscale is assessed from 4 points (lack of symptoms) to 20 points (worst symptoms possible).	Day 29 ± 1 (Visit 3)
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	Normally, the total number of points should not exceed 30. If the total score on any of the subscales (General Fatigue, Reduced Activity, Decreased Motivation, Physical Fatigue, Mental Fatigue) is above 12, it may serve as preliminary grounds for diagnosing "asthenic syndrome." Each subscale is assessed from 4 points (lack of symptoms) to 20 points (worst symptoms possible).	Day 29 ± 1 (Visit 3)
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)	Normally, the total number of points should not exceed 30. If the total score on any of the subscales (General Fatigue, Reduced Activity, Decreased Motivation, Physical Fatigue, Mental Fatigue) is above 12, it may serve as preliminary grounds for diagnosing "asthenic syndrome." Each subscale is assessed from 4 points (lack of symptoms) to 20 points (worst symptoms possible).	Day 29 ± 1 (Visit 3)
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)	Normally, the total number of points should not exceed 30. If the total score on any of the subscales (General Fatigue, Reduced Activity, Decreased Motivation, Physical Fatigue, Mental Fatigue) is above 12, it may serve as preliminary grounds for diagnosing "asthenic syndrome." Each subscale is assessed from 4 points (lack of symptoms) to 20 points (worst symptoms possible).	Day 29 ± 1 (Visit 3)

Collaborators and Investigators

• Sponsor: Valenta Pharm JSC

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: February 17, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Somatoform Disorders; Anxiety Disorders; Adjustment Disorders; Neurasthenia; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Second-Generation; Tryptophan
• Other Study ID Numbers: RAN-04-05-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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