Clinical trial NCT05586789: A Study of the Efficacy and Safety of Ranquilon Tablets in Patients With Anxiety in Neurasthenia and Adjustment Disorders
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Phase III Clinical Trial to Examine the Clinical Efficacy and Safety of Ranquilon, 1 mg Tablets in Patients With Anxiety in Neurasthenia and Adjustment Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anxiety
Neurasthenia
Adjustment Disorders
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2022-10-19
Enrollment: 220
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: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 29 ± 1 of the study
Secondary outcomes:
measure: Proportion of patients with a significant, i.e., 50% or greater reduction in HARS anxiety level on Day 15 ± 1 (Visit 2)
timeFrame: Day 15 ± 1 of the study
measure: Change in HARS anxiety level on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 15 ± 1 and Day 29 ± 1 of the study
measure: Proportion of patients with HARS anxiety scores reduced to 17 or less on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3)
timeFrame: Day 15 ± 1 and Day 29 ± 1 of the study
measure: Time to decrease the HARS anxiety level to a score of 17 or less
timeFrame: 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
measure: 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)
timeFrame: Day 15 ± 1 and Day 29 ± 1 of the study
measure: 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)
timeFrame: Day 15 ± 1 and Day 29 ± 1 of the study
measure: Time to significant or marked improvement - achieving a score of 1 or 2 on the CGI-i scale
timeFrame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, or an early termination visit, whichever came first
measure: Time to decrease in severity of condition to 2 points or to 1 point or CGI-s scale
timeFrame: 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
measure: Absolute value of the patient's CGI-i score by Days 15 ± 1 (Visit 2) and 29 ± 1 (Visit 3)
timeFrame: Day 15 ± 1 and Day 29 ± 1 of the study
measure: Change in patient severity on the CGI-s scale by Days 15 ± 1 (Visit 2) and 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 15 ± 1 and Day 29 ± 1 of the study
measure: 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
timeFrame: Day 15 ± 1 and Day 29 ± 1 of the study
measure: Time to decrease the MFI-20 cumulative score to 30 points or less
timeFrame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, or an early termination visit, whichever came first
measure: Time to decrease the MFI-20 cumulative score by 25% and 50% from baseline
timeFrame: Screening, Day 15 ± 1, Day 29 ± 1 of the study, or an early termination visit, whichever came first
measure: 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
timeFrame: Day 15 ± 1 and Day 29 ± 1
measure: 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
timeFrame: Day 15 ± 1 and Day 29 ± 1
measure: 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)
timeFrame: Day 15 ± 1 and Day 29 ± 1
measure: Change in Spielberger personality anxiety level on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 15 ± 1 and Day 29 ± 1
measure: Change in situational anxiety levels on the Spielberger questionnaire on Day 15 ± 1 (Visit 2) and Day 29 ± 1 (Visit 3) compared to baseline
timeFrame: Day 15 ± 1 and Day 29 ± 1
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 44 ± 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 44 ± 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 44 ± 1 for each participant
measure: Safety and Tolerability: vital signs - systolic blood pressure (SBP)
timeFrame: 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
measure: Safety and Tolerability: vital signs - diastolic blood pressure (DBP)
timeFrame: 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
measure: Safety and Tolerability: vital signs - respiratory rate (RR)
timeFrame: 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
measure: Safety and Tolerability: vital signs - heart rate (HR)
timeFrame: 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
measure: Safety and Tolerability: vital signs - body temperature
timeFrame: 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
measure: Safety and Tolerability: physical examination results
timeFrame: 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
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate
timeFrame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval
timeFrame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex
timeFrame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval (QTc)
timeFrame: Screening, day 29, or on the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - hemoglobin
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - hematocrit
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - red blood cells
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - white blood cells
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - platelets
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - erythrocyte sedimentation rate
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - lymphocytes
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - eosinophils
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - monocytes
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - basophils
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: complete blood count - neutrophils
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - total cholesterol
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - total protein
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - glucose
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - creatinine
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - alanine transaminase (ALT)
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - aspartate transaminase (AST)
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - total bilirubin
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - direct bilirubin
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - alkaline phosphatase (ALP)
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: blood test results - urea
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - color
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - transparency
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - specific gravity
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - pH
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - glucose
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - protein
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - ketones
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
measure: Safety and Tolerability: urinalysis - urobilinogen
timeFrame: Screening, Day 29 or the early termination visit, whichever came first, within 44 days of study participation
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: Nizhny Novgorod
country: Russian Federation
facility: State Budgetary Health Institution of Nizhny Novgorod Oblast "Clinical Psychiatric Hospital No. 1 of Nizhny Novgorod. Nizhny Novgorod"
city: Perm
country: Russian Federation
facility: Professors' Clinic LLC.
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Research Center Eco-Security"
city: Saint Petersburg
country: Russian Federation
facility: EosMED JSC
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Energy of Health"
city: Saint Petersburg
country: Russian Federation
facility: LLC "Aurora MedFort"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Research Center Eco-Safety"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Meili"
city: Saratov
country: Russian Federation
facility: Saratov City Psychoneurological Dispensary
Study officials:
References: