Study to Assess Efficacy and Safety of XC221 200 mg in the Treatment of Influenza or Other ARVI

Study Overview
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Brief Summary
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The innovative drug XC221 is planned for use in treatment of acute respiratory viral infections in a double-blind, randomized, placebo-controlled, comparative multicenter study assessing the safety, tolerability and efficacy of XC221 at a dose of 200 mg per day in patients with uncomplicated influenza or other acute respiratory viral infections during the 3-days treatment.

Detailed Description
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A double-blind, randomized, placebo-controlled, comparative multicenter study in two groups. A total of 120 patients with uncomplicated influenza or other acute respiratory viral infections are planned to be randomized. Patients will be randomized into 2 groups: 60 patients in the treatment group 200 mg XC221 and 60 patients in the placebo group. The purpose of the clinical trial is to assess the safety, tolerability and efficacy of the drug XC21 in treatment of influenza or other acute respiratory viral infections. The primary objective is to demonstrate the difference between the groups in the time of the onset of sustained improvement in clinical symptoms according to the Modified Jackson Scale. The study will consist of the following periods: screening (duration not more than 36 hours from the moment of the first symptoms of the disease), treatment period (3 days), follow-up period (11 ± 1 days after completion of treatment with the study drug/placebo). The duration of participation in the study for each patient is no more than 16 days and 12 hours.

Official Title
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Double-blind Randomized Placebo-controlled Comparative Multicenter Study to Assess the Safety, Tolerability and Efficacy of XC221 in a Dose of 200mg Per Day in Patients With Uncomplicated Influenza or Other ARVI

Conditions
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Influenza, Acute Respiratory Viral Infections

Intervention / Treatment
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* Drug: XC221
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both sexes aged 18 years and older. Clinically diagnosed influenza or ARVI mild or moderate severity. Patient's body temperature ≥37.5ºС and at least 1 symptom from Modified Jackson Scale estimated more than 2 points. Uncomplicated course of influenza or ARVI based on clinical estimations. The first 36 hours from the beginning of symptoms of influenza or ARVI. Women of reproductive age (who are not in menopause and who have not undergone surgical sterilization) and men who have sexual activity should use a reliable method of contraception (acceptable methods of contraception in this study are: intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptives, a double barrier method (condom and diaphragm with spermicide) throughout the study period. Compliance with the treatment regimen, visits and laboratory examinations provided by the protocol. Signed Informed Consent Form. Exclusion Criteria: Complications of influenza or ARVI (including the presence / development of bacterial infection). The need for inpatient treatment of influenza and ARVI. Hypersensitivity to excipients of the drug XC221 or placebo. Antiviral medications 7 days prior to screening (antiviral agents, interferons and interferon inducers, drugs that have immunomodulating action) or anti-infective agents of systemic or local action. Severe infection with signs of cardiovascular insufficiency development and other manifestations of infectious-toxic shock, as well as with the presence of neuroinfection syndrome (encephalic and meningoencephalic reactions, polyradiculoneuritis, neuritis). Signs of of viral pneumonia symptoms (the presence of two or more of the following symptoms): dyspnea, chest pain when coughing, systemic cyanosis, dullness of percussion sound with a symmetrical evaluation of the upper and lower sections of the lungs). Infectious diseases during the last week before including into the study. Bronchial asthma, COPD, pulmonary emphysema in history. History of increased convulsive activity. Severe, decompensated or unstable somatic diseases (any diseases or conditions that are life-threatening or may worsen the patient's prognosis, and make him/her ineligible for the clinical study). History of oncological diseases, HIV, tuberculosis. Drug or alcohol abuse. Lactose intolerance, lactase deficiency, glucose-galactose malabsorption. Participation in any other clinical trial in the last 90 days. Pregnancy or lactation. Military or prison populations. Impossibility or inability to comply with the study procedures. A member of the investigator's family or other person interested in the results of the study. Deviations from laboratory standards, which prevent the inclusion of the patient in the study according to the Investigator. A history of kidney failure.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XC221<br>XC221 200 mg orally. 2 tablets of XC221 100 mg once daily during 3 days of treatment period | Drug: XC221<br>* Participants will receive 200 mg XC221 once a day during 3 days<br>|
| Placebo Comparator: Placebo<br>Placebo orally. 2 tablets of Placebo once daily during 3 days of treatment period | Drug: Placebo<br>* Participants will receive Placebo once a day during 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to sustained improvement in clinical symptoms according to the Modified Jackson Scale for measuring respiratory symptoms. | The time before the onset of sustained improvement in clinical symptoms according to the Modified Jackson Scale (no more than 1 point for each symptom), measured in hours from the moment of the first dose of the drug. Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. | From the moment of the first dose up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time before the onset of persistent improvement in clinical symptoms according to the Modified Jackson Scale for measuring respiratory symptoms (0 points). | The time of the first assessment of 3 consecutive ratings on the Modified Jackson Scale, in which all the clinical symptoms were 0 points. Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. | From the moment of the first dose up to Day 14 | 
| The time before the onset of persistent improvement in clinical symptoms according to the Modified Jackson Scale for measuring respiratory symptoms. | Total score of no more than 3 points, when there is no more than 1 point for each symptom, measured in hours from the moment of taking the first dose of the drug. Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. | From the moment of the first dose up to Day 14 | 
| Time to normalization of body temperature. | Measured in hours. Normalization means the establishment of body temperature below 37° C without a rise above these values in the subsequent observation period. | From the moment of the first dose up to Day 14 | 
| The average score according to the Modified Jackson Scale for measuring respiratory symptoms at the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th days. | The average score according to the Modified Jackson Scale on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th days. Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. | From the moment of the first dose up to Day 14 | 
| The proportion of patients with a sum of not more than 3 points according to the Modified Jackson Scale for measuring respiratory symptoms at the 1st, 2nd, 3rd, 4th, 5th, 6th , The 7th, 8th days | Score for each symptom should be no higher than 1 point at the 1st, 2nd, 3rd, 4th, 5th, 6th , The 7th, 8th days from the moment of the start of treatment. Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. | From the moment of the first dose up to Day 14 | 
| The proportion of patients with the normalization of body temperature on the first - the 14th days from the start of treatment; |  | From the moment of the first dose up to Day 14 | 
| Time to disappearance (0 points) of each of the symptoms according to the Modified Jackson Scale for measuring respiratory symptoms. | Symptom (sneezing, rhinorrhea, nasal congestion, cough, fever, malaise, chills, headache, myalgia, sore throat, tickling, hoarseness) manifested at the level of 2 or 3 points at the first assessment at Visit 0 (Day 0). Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. | From the moment of the first dose up to Day 14 | 
| The proportion of patients with 0 points score for each of the symptoms according to the Modified Jackson Scale for measuring respiratory symptoms. | Modified Jackson Scale (sneezing, rhinorrhea, nasal congestion, cough, fever, malaise, chills, headache, myalgia, sore throat, tickling, hoarseness) at the 2nd, 3rd 2nd, 4th, 5th, 6th, 7th and 8th days from the moment of the start of treatment in a population of patients with the corresponding symptom shown at the level of 2 or 3 points at Visit 0 (Day 0). Modified Jackson Scale measures individuals' subjective ratings the severity of 12 respiratory symptoms. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 32 points) is a sum of the point for each symptom. | From the moment of the first dose up to Day 14 | 
| The proportion of patients with a detected viral pathogen | The proportion of patients with a detected viral pathogen at Visit 0, Visit 4 and Visit 6. | From the moment of the first dose up to Day 14 | 
| The proportion of patients with a detected viral pathogen at Visit 4 and Visit 6 compared with the initial proportion of such patients in the XC221. |  | From the moment of the first dose up to Day 14 | 
| The frequency of adverse events (AEs) and serious adverse events (SAEs) in the XC221 treatment group and in the placebo group. |  | From the moment of the first dose up to Day 14 |