XC8 in the Treatment of Patients With Acute Respiratory Viral Infection

Study Overview
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Brief Summary
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A multicenter double-blind, randomized, placebo-controlled, parallel-group comparative Phase II / III clinical study to assess safety, tolerability, efficacy and optimal dose ranging of XC8 vs. placebo in patients with uncomplicated influenza or other ARVI during a 5-day treatment. The primary objective of the study was to demonstrate the difference in time before the onset of a sustained improvement in clinical symptoms according to the Severity Rating Scale for ARVI, and to determine the optimal dose of XC8 in the treatment of influenza and other ARVI.

Detailed Description
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Twenty-three Russian centers were approved for participation in this study. Twenty centers were initiated. Patients were enrolled in 18 centers. The study consisted of two parts: phase II and phase III. Each of the parts included 3 periods: screening, treatment, follow-up. In the first part of the study (Phase II), all eligible patients were randomized into 4 groups (groups A, B, C, and D) in a 1:1:1:1 ratio: Group A - XC8 20 mg daily (40 patients); Group B - XC8 100 mg daily (40 patients); Group C - XC8 200 mg daily (40 patients); Group D - placebo (40 patients). Interim analysis was planned after the end of the first part of the study (Phase II). Based on the results of the interim analysis, the most promising XC8 dose group was selected and the necessary set was calculated to compare this group with the placebo group by the primary endpoint in a pooled set using an adaptive design with type I error control. In the second part of the study (Phase III), all eligible patients were randomized into 2 groups (groups C and D) in a 1:1 ratio: Group C - XC8 200 mg daily (80 patients); Group D - placebo (80 Patients). During the treatment period (5 days), patients received XC8 / placebo daily on a background of standard symptomatic therapy. The follow-up period lasted for 9 days.

Official Title
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Clinical Study to Assess Efficacy, Safety, Tolerability and Optimal Dose Ranging of XC8 in Doses 20, 100 and 200 mg Once Daily in Patients With Uncomplicated Influenza or Other Acute Respiratory Viral Infections (ARVI)

Conditions
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Influenza, Acute Respiratory Infection

Intervention / Treatment
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* Drug: XC8 20 mg
* Drug: XC8 100 mg
* Drug: XC8 200 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 to 45 years (inclusively). Clinically diagnosed influenza or other acute or moderate ARVI based on the patient's body temperature ≥37.5ºС, nasal congestion or profuse rhinorrhea and at least 1 of the following symptoms of intoxication: headache, general malaise, myalgia, pain in the eyeballs. Uncomplicated course of ARVI or influenza. The onset of symptoms no more than 36h prior to the inclusion into the study. 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 Informant Consent Form. Exclusion Criteria: The patient will be deemed ineligible for the study meeting any of the following criteria: Complicated course of influenza or ARVI (including the presence / development of bacterial infection). Antiviral medications in 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 the development of viral pneumonia (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. History of bronchial asthma. 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. Hypersensitivity to excipients of the XC8. Diabetes mellitus, lactose intolerance, lactase deficiency. Drug or alcohol abuse. 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 Abnormal laboratory results, which, according to the study doctor, interfere with the patient's inclusion in the study. History of renal insufficiency. Only for patients participating in Phase III study: Patient involvement in the first part of the study (Phase II) of FLU-XC8-01. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: XC8 20 mg and Placebo (Group A)<br>XC8 20 mg orally. 2 tablets of XC8 10 mg +2 tablets of Placebo 100 mg (in total 4 tablets) once daily during 5 days of treatment period | Drug: XC8 20 mg<br>* once daily during 5 days.<br>* Other names: Нistamine glutarimide;|
| Experimental: XC8 100 mg and Placebo (Group B)<br>XC8 100 mg orally. 1 tablet of XC8 100 mg +2 tablets of Placebo 10 mg + 1 tablet of Placebo 100 mg (in total 4 tablets) once daily during 5 days of treatment period | Drug: XC8 100 mg<br>* once daily during 5 days.<br>* Other names: Нistamine glutarimide;|
| Experimental: XC8 200 mg and Placebo (Group C)<br>XC8 200 mg orally. 2 tablets of XC8 100 mg +2 tablets of Placebo 10 mg (in total 4 tablets) once daily during 5 days of treatment period. | Drug: XC8 200 mg<br>* once daily during 5 days.<br>* Other names: Нistamine glutarimide;|
| Placebo Comparator: Placebo (Group D)<br>Placebo orally. | Drug: XC8 20 mg<br>* once daily during 5 days.<br>* Other names: Нistamine glutarimide;Drug: XC8 100 mg<br>* once daily during 5 days.<br>* Other names: Нistamine glutarimide;Drug: XC8 200 mg<br>* once daily during 5 days.<br>* Other names: Нistamine glutarimide;Drug: Placebo<br>* once daily during 5 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 | Severity Rating Scale for ARVI (<2 points, provided that there is ≤ 1 point for one symptom) with temperature normalization (<37°C) (estimated by Kaplan-Meier), established according to patient diaries. | up to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body temperature below 37°C without further elevation | Time to normalization of body temperature since the symptoms onset, measured in hours | up to Day 8 |