A Study of the Efficacy and Safety of Ranquilon Tablets in Patients With Anxiety in Neurasthenia and Adjustment Disorders

Valenta Pharm JSC220 enrolled

Overview

The primary objective of the study is to evaluate the efficacy of Ranquilon, 1 mg tablets, at a dose of 6 mg/day compared to placebo for the treatment of patients with anxiety in neurasthenia and adjustment disorder. An additional study objective was to evaluate the safety of Ranquilon, 1 mg tablets, at a dose of 6 mg/day compared to placebo in patients with anxiety in neurasthenia and adjustment disorder.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

220

Conditions

Anxiety Neurasthenia Adjustment Disorders

Interventions

RanquilonDRUG

Two 1 mg tablets 3 times per day for 28 days

PlaceboDRUG

Two tablets 3 times per day for 28 days

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Men and women between the ages of 18 and 70 2. Presence of written consent to participate in the study in accordance with applicable law 3. Patients with anxiety and diagnoses based on ICD-10 criteria: neurasthenia (F48.0) or adjustment disorder (F43.2) 4. HARS anxiety scores of 18-24 5. Severity of asthenia on the Asthenia Self Assessment Scale (MFI-20) of more than 50 points 6. Hamilton Depression Assessment Scale (HAMD-17) score \< 6 7. CGI-s scale score of at least 4 8. Negative pregnancy test for women of preserved reproductive potential 9. Consent to use effective contraception for the duration of the study and 30 days after completion (for women of unresolved reproductive potential and men) 10. Ability to understand the requirements for study participants, to give written consent to participate in the study (including the use and communication of patient health information relevant to the study) and to comply with the procedures of the study protocol Exclusion Criteria: 1. Known intolerance to the active ingredient and/or excipients in the study drug/placebo of the study drug 2. Known presence of lactase deficiency, lactose intolerance, glucose-galactose malabsorption or galactose intolerance 3. Patients who require concomitant therapy prohibited in this study (MAO inhibitors, antidepressants, neuroleptics, anxiolytics and sedatives (including herbal), sleeping pills when used on a continuous basis), or have taken these drugs within the last month 4. Established or suspected alcohol/drug use at the time of screening or randomization, and/or a history of alcohol, drug or drug dependence 5. Presence of cancer, including a history of cancer (with the exception of a cured tumor with sustained remission for more than 5 years) 6. Presence of tuberculosis, including a history of tuberculosis 7. The presence of HIV, chronic viral hepatitis B/C, syphilis (including a history), or a positive test for HIV, hepatitis B/C, syphilis at screening 8. Patients with a diagnosis established on the basis of ICD-10 criteria: other anxiety disorders (F41) 9. Schizophrenia, schizoaffective, affective and panic disorders 10. Acute psychosis (endogenous-procedural, organic or somatogenic), including history 11. Organic lesions of the central nervous system of traumatic and alcoholic genesis 12. Postencephalitic syndrome 13. Brain tumors, including in the anamnesis 14. Degenerative diseases of the central nervous system (CNS), in particular, multiple sclerosis 15. Depression, including a history of depression 16. Generalized anxiety disorder, including a history 17. Suicidal thoughts or ideas; a history of suicide attempts 18. Epilepsy, seizures, including a history of seizures 19. Diabetes mellitus at the stage of decompensation 20. Established diagnosis of chronic kidney disease stage 3A or higher, or glomerular filtration rate (GFR) calculated by the Cockcroft-Gault formula = 59 ml/min/1.73 m2 or less 21. Established diagnosis of hepatic failure of any severity, or elevated ALT, AST or total bilirubin, urea \>3 times the upper limit of normal values 22. Conditions after major surgical interventions, if less than six months have elapsed since the intervention 23. Chronic heart failure New York Heart Association (NYHA) functional class III-IV 24. Severe, decompensated, or unstable disease (any disease or condition that threatens the patient's life or worsens the patient's prognosis, or makes it impossible to perform a clinical trial in the patient) 25. Pregnant women, women breastfeeding, or women planning to become pregnant during the study and 30 days after study participation ends 26. Refusal by the patient to use approved contraception or to completely abstain from sexual intercourse during the entire period of study participation, beginning at Visit 0, and for 30 days after completion of study participation 27. Patient's current or planned participation in psychological or psychotherapeutic interventions designed to treat an anxiety disorder during the course of the clinical trial 28. Participation in any other clinical trial within 90 days prior to the screening period 29. Lack of willingness to cooperate on the part of the patient 30. Other reasons that, in the opinion of the investigator, prevent the patient from participating in the study or pose an unreasonable risk to the patient Withdrawal Criteria: 1. Patient's desire to stop participating in the study (withdrawal of informed consent) Each patient has the right to stop participating in the study at any time without giving a reason. Withdrawal from the study will not affect the medical care provided to the patient in the future. 2. A decision by the research physician that the patient should be excluded is in the patient's own best interest 3. Patient refuses to cooperate with the investigator or is undisciplined 4. Causes/occurrence of situations during the study that threaten patient safety (e.g., hypersensitivity reactions, SAE, etc.) 5. Inclusion of a patient in the study with inclusion/inclusion criteria not met (prior to randomization) 6. Significant violation of the treatment regimen A significant violation is defined as a) skipping study drug/placebo for 2 consecutive full days or more, or b) taking, in total, \< 80% or \>120% of the full course (full course = 168 pills) 7. Positive pregnancy test 8. Confirmed diagnosis of COVID-19 9. Occurrence in the course of the study of other reasons that prevent the study according to the protocol 10. Death of a patient

Locations (10)

Engels Psychiatric Hospital State Health Care Institution of the Ministry of Health of the Saratov Region

Engel's, Russia

State Budgetary Health Institution of Nizhny Novgorod Oblast "Clinical Psychiatric Hospital No. 1 of Nizhny Novgorod. Nizhny Novgorod"

Nizhny Novgorod, Russia

Professors' Clinic LLC.

Perm, Russia

Outcomes

Primary Outcomes

Change in patient status on the Hamilton Anxiety Rating Scale (HARS): Percentage of patients with a significant, i.e., 50% or greater reduction from baseline, in HARS anxiety levels on Day 29 ± 1

HARS scale includes 14 items, each of which is rated on the Likken scale. Of these, 13 items relate to the manifestation of anxiety in daily life, 14 items relate to the manifestation of anxiety during examinations. The sum of the scores may range from 0 to 56, with scores 0 to 7 corresponding to the absence of anxiety, 8 to 17 to the presence of symptoms of anxiety disorder, 18 to 24 to moderate severity of anxiety disorder, and 25 to 56 to severe severity of anxiety disorder.

Time frame: Day 29 ± 1 of the study

Secondary Outcomes

Proportion of patients with a significant, i.e., 50% or greater reduction in HARS anxiety level on Day 15 ± 1 (Visit 2)

Time frame: Day 15 ± 1 of the study

Change in HARS anxiety level on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) compared to baseline

Time frame: Day 15 ± 1 and Day 29 ± 1 of the study

Proportion of patients with HARS anxiety scores reduced to 17 or less on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3)

Data from ClinicalTrials.gov

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Limited Liability Company "Research Center Eco-Security"

Saint Petersburg, Russia

EosMED JSC

Saint Petersburg, Russia

Limited Liability Company "Energy of Health"

Saint Petersburg, Russia

LLC "Aurora MedFort"

Saint Petersburg, Russia

Limited Liability Company "Research Center Eco-Safety"

Saint Petersburg, Russia

Limited Liability Company "Meili"

Saint Petersburg, Russia

Saratov City Psychoneurological Dispensary

Saratov, Russia

Time frame: Day 15 ± 1 and Day 29 ± 1 of the study

Time to decrease the HARS anxiety level to a score of 17 or less

Time frame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, the end of the study (Day 44 ± 1) or an early termination visit, whichever came first

Proportion of patients with significant and marked improvement as assessed by the physician (Clinical Global Impression - improvement (CGI-i) score 1 or 2) at Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3)

The Clinical Global Impression Scale (CGI) includes two subscales: one for severity of symptoms and one for progression of symptoms with treatment. The first subscale is called Clinical Global Impression - severity (CGI-s) and the second subscale is Clinical Global Impression - improvement (CGI-i). CGI-s includes scores from 0 (healthy) to 7 (very severe); CGI-i includes scores from 1 (marked improvement) to 7 (marked deterioration)

Time frame: Day 15 ± 1 and Day 29 ± 1 of the study

Proportion of patients with a CGI-s score of 1 or 2 as assessed by the physician (healthy or borderline disorder) on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3)

Time frame: Day 15 ± 1 and Day 29 ± 1 of the study

Time to significant or marked improvement - achieving a score of 1 or 2 on the CGI-i scale

Time frame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, or an early termination visit, whichever came first

Time to decrease in severity of condition to 2 points or to 1 point or CGI-s scale

Time frame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, the end of the study (Day 44 ± 1) or an early termination visit, whichever came first

Absolute value of the patient's CGI-i score by Days 15 ± 1 (Visit 2) and 29 ± 1 (Visit 3)

Time frame: Day 15 ± 1 and Day 29 ± 1 of the study

Change in patient severity on the CGI-s scale by Days 15 ± 1 (Visit 2) and 29 ± 1 (Visit 3) compared to baseline

Time frame: Day 15 ± 1 and Day 29 ± 1 of the study

Change in the Multidimensional Fatigue Fatigue Inventory (MFI-20) total score on Day 15 ± 1 (Visit 2) and 29 ± 1 (Visit 3) compared to baseline

The Multidimensional Fatigue Fatigue Inventory (MFI-20) provides a subjective quantitative assessment of the overall severity of asthenia and its various aspects. This scale consists of 20 items reflecting the main components of asthenic syndrome, such as: general asthenia, physical asthenia, mental asthenia, decreased activity and decreased motivation. The patient was given an opportunity to rate the mentioned items to his/her condition on a five-point scale. The score of the scale is the sum of the points of its individual constituent items and can vary in the range from 5 to 25 points. Normally, the total number of points should not exceed 30. If the total score on one of the subscales was higher than 12, this could be a preliminary ground for classifying the condition as an asthenic syndrome

Time frame: Day 15 ± 1 and Day 29 ± 1 of the study

Time to decrease the MFI-20 cumulative score to 30 points or less

Time frame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, or an early termination visit, whichever came first

Time to decrease the MFI-20 cumulative score by 25% and 50% from baseline

Time frame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, or an early termination visit, whichever came first

Proportion of patients with a 25% reduction in MFI-20 total score on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) from baseline

Time frame: Day 15 ± 1 and Day 29 ± 1

Proportion of patients with a 50% reduction in MFI-20 total score on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) from baseline

Time frame: Day 15 ± 1 and Day 29 ± 1

Proportion of patients with a decrease in their MFI-20 cumulative score to 30 on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3)

Time frame: Day 15 ± 1 and Day 29 ± 1

Change in Spielberger personality anxiety level on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) compared to baseline

The Spielberger Questionnaire includes a series of statements describing personal and situational anxiety, the answers to which are scored from 1 (least severe or prolonged) to 4 (most severe or prolonged). The patient reads the statements and independently chooses the most appropriate frequency for each statement. When analyzing the results of the self-assessment, you should keep in mind that the overall total for each of the subscales may range from 20 to 80 points. The higher the total score, the higher the level of anxiety (situational or personal).

Time frame: Day 15 ± 1 and Day 29 ± 1

Change in situational anxiety levels on the Spielberger questionnaire on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) compared to baseline

Time frame: Day 15 ± 1 and Day 29 ± 1

Safety and Tolerability: adverse event (AE) rate

Number and frequency of adverse events (AEs) or serious AEs (SAEs)

Time frame: 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 44 ± 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

Safety and Tolerability: treatment discontinuation

Percentage of patients who discontinued treatment due to the occurrence of AEs/SAEs

Safety and Tolerability: vital signs - systolic blood pressure (SBP)

SBP, mmHg

Time frame: Screening, day 1, day 15, day 29, and day 44 of the study or on the early termination visit, whichever came first, within 44 days of study participation

Safety and Tolerability: vital signs - diastolic blood pressure (DBP)

DBP, mmHg

Time frame: Screening, day 1, day 15, day 29, and day 44 of the study or on the early termination visit, whichever came first, within 44 days of study participation

Safety and Tolerability: vital signs - respiratory rate (RR)

RR, breaths per minute

Time frame: Screening, day 1, day 15, day 29, and day 44 of the study or on the early termination visit, whichever came first, within 44 days of study participation

Safety and Tolerability: vital signs - heart rate (HR)

HR, beats per minute

Time frame: Screening, day 1, day 15, day 29, and day 44 of the study or on the early termination visit, whichever came first, within 44 days of study participation

Safety and Tolerability: vital signs - body temperature

Body temperature, centigrade scale

Time frame: Screening, day 1, day 15, day 29, and day 44 of the study or on the early termination visit, whichever came first, within 44 days of study participation

Safety and Tolerability: physical examination results

Physical examination will follow the general rules of internal medicine: general examination, examination of mucous membranes and skin, including palpation of lymph nodes, evaluation of the musculoskeletal system, palpation, percussion, and auscultation of the main organ systems (cardiovascular, respiratory, digestive, and urinary systems) will be performed sequentially

Time frame: Screening, day 1, day 15, day 29, and day 44 of the study or on the early termination visit, whichever came first, within 44 days of study participation

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)

Time frame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation

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)

Time frame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation

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)

Time frame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation

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)

Time frame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation

Safety and Tolerability: complete blood count - hemoglobin

Hemoglobin, g/dL