Efficacy and Safety of Enisamium Iodide for the Treatment of Acute Respiratory Viral Infections, Including Influenza.

Study Overview
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Brief Summary
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This randomized, single blind clinical study was conducted to investigate the clinical efficacy and safety of the drug Amizon (enisamium iodide), in comparison with placebo for the treatment of patients with acute respiratory viral infections (ARVI), including influenza. Enisamium iodide is an antiviral small molecule. Adult patients were enrolled and randomised into 2 groups. On the first day of the onset of symptoms of ARVI, one group of patients took Amizon tablets (active ingredient enisamium iodide) for 7 days; the other group of patients took matching placebo tablets for 7 days. Examination and observation of all participants was done for up to 14 days after the first intake of the study drug. The effect of treatment was assessed by subjective reporting of the symptoms of ARVI and influenza, using a predefined symptom scale score system. Objective assessment was performed by measuring vitals signs, laboratory tests (including blood and urine assessment), as well as evaluating the immune status (including measuring the relative concentration of interferon and immunoglobulins).

Detailed Description
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Numerous studies have shown that influenza vaccines, prepared against the relevant epidemic seasonal vaccine strains, are an effective remedy in prevention of this mass disease and are able to protect about 80% of otherwise healthy children and adults. However, to develop vaccines against the emerging new pandemic strain of the influenza virus and produce them in the necessary amounts requires at least 6 months. During such interim periods, sufficient protection of the population is essential by effective measures for treatment and prevention of influenza. This randomized, single-blind, clinical study was conducted to investigate the clinical efficacy and safety of the drug Amizon (N-methyl-4-benzylcarbamidopyridinium iodide, international nonproprietary name enisamium iodide) compared with placebo, for the treatment of patients with ARVI, including influenza. Enisamium iodide is an antiviral small molecule. Enisamium can directly inhibit influenza viral RNA replication. The study design was: randomised, single-blind, 2 parallel groups. Adult patients (18-60 y) with symptoms of ARVI, including influenza took either Amizon tablets (active ingredient enisamium iodide) for 7 days; in the control group patients took placebo tablets for 7 days. Study visits occurred on Day 0 (screening, examination, check inclusion/exclusion criteria, enrollment, randomization, and first intake of study drug); further study visits were on Day 3, Day 7, and Day 14. The effect of treatment was assessed by questioning the patients regarding ARVI and influenza symptoms that included pain, headache, general weakness, sore throat, pain in the joints, fatigue, runny and itchy nose. The severity of symptoms was recorded using a 4-point Likert scale. Further evaluation of the treatment was performed by measuring the vitals signs, laboratory tests that included blood and urine analysis, biochemical analysis, as well as assessing the immune status (including measuring the absolute lymphocytes count, and evaluating the relative concentration of interferon (IFN)-alpha and IFN-gamma, and immunoglobulins (IgA, IgM, and IgG).

Official Title
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A Prospective Single-blind Comparative Clinical Study of Efficacy and Safety of Amizon 0.25 g Tablets, Manufactured by Farmak JSC, in Patients With ARVI, Including Influenza.

Conditions
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Human Influenza, Acute Respiratory Viral Infections

Intervention / Treatment
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* Drug: Enisamium Iodide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged between 18 to 60 years Patients with ARVI, including influenza, starting not later than for 1 day prior to inclusion in the study: The body temperature measured axillary above 37.2 °C Presence of one of the signs of respiratory disease (runny nose, cough, pain / tickling in the throat) Presence of one of the systemic symptoms (weakness, myalgia, headache , chills, sweating) Provide written informed consent Ability to understand the nature of the study and provide written informed consent in accordance with Good Clinical Practice (GCP) and local law Exclusion Criteria: Age over 60 years and under 18 years old Presence of allergic reactions Intolerance to NSAIDs and iodine-containing drugs Hypersensitivity to the components of the drug Mental illness that impedes compliance with the research procedure Pregnancy or breast-feeding Presence of acute, clinically significant respiratory and cardio vascular insufficiency, functional disorders of liver, kidney, digestive tract (ulcer disease) determined at physical examination or by laboratory screening tests Presence of congenital defects or serious chronic disease of the lungs, kidneys, cardiovascular system, nervous system, metabolic disorders, psychiatric disorders, confirmed by patients history or during initial examination The use of preparations of blood cytokine immunoglobulin in for 3 months prior to the study Chronic use of alcohol and / or drugs Presence or history of cancer diseases, HIV, hepatitis B and C Application of immunosuppressive or immunomodulatory drugs for 6-months prior to the study Women of child-bearing potential and who do not use acceptable measure of contraception or do not plan to use those throughout the study Any clinical condition that, according to the investigator, will not allow to safely carry out the protocol and take the studied drugs without risk to health Patients receiving antiviral therapy, Participation in other clinical trials at the present time or during the last 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Group 1 - Active Treatment<br>Patient who were randomized into Group 1 ingested Amizon tablets 0.5 g (2 tablets) after a meal, 3 times a day, for 7 days; each tablet contains 0.25 g of enisamium iodide. | Drug: Enisamium Iodide<br>* Patients ingested Amizon tablets after meal without chewing as follows: 2 tablets (total dose 0.5 g) 3 times a day, for 7 days. Each tablet contains 0.25 g of Nmethyl- 4-N-methyl-4-benzylcarbamidopyridinium iodide (INN enisamium iodide).<br>* Other names: Amizon;|
| Placebo Comparator: Group 2 - Placebo<br>Patient who were randomized into Group 2 ingested placebo tablets after a meal, at the dose 0.5 g (2 tablets), 3 times a day, for 7 days. | Drug: Placebo<br>* Patients ingested placebo tablets after meal without chewing in the dose 0.5 g (2 tablets), 3 times a day, for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Clinical improvement from Day 3 after therapy start | Evaluate the number of patients in the treatment and the placebo groups regarding clinical improvement from Day 3 after therapy start. Clinical improvement was assessed by the investigator from scores of objective and subjective data, relating to the severity of clinical symptoms of ARVI, including influenza. Objective symptoms were assessed using the following score system: normal or abnormal blood pressure was counted 0 or 4 score points; lung auscultation was counted 0 for vesicular breath sound and wheezing or crepitation were scored 2 or 4 points, respectively; clear and rhythmic heart sounds were each scored 0 points, whereas noisy and arrhythmic heart sounds were scored 2 points each. The subjective symptoms were assessed using a 4-point Likert scale, ranging from 1 (absent) to 4 (severe). | Day 0, 3, 7, 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Time of disappearance of respiratory tract affection symptoms | Evaluate the time of disappearance of respiratory tract symptoms (rhinitis, pharyngitis, laryngitis, tracheitis, bronchitis, cough). Evaluate the general state of health, condition of cutaneous coverings, oral mucosa and tonsils, peripheral lymph nodes, abdominal cavity organs, nervous and musculoskeletal system, lung and heart percussion and auscultation data were assessed. Evaluate the intensity and duration of the disease symptoms: temperature response, catarrhal events in nasopharynx and other respiratory tract parts. Clinical improvement was assessed by the visit day on which the symptoms were absent (score 1 on the Likert scale, as described for Outcome 1). | Day 0, 3, 7, 14 | 
| Efficacy - Body temperature normalization | Monitor body temperature. | Day 0, 3, 7, 14 | 
| Efficacy - General symptoms of ARVI including influenza | Time of disappearance of general symptoms -- ARVI, including influenza. Time of disappearance of general symptoms relating to the respiratory tract, including weakness, headache, myalgia, chills, sore throat, and cough. | Day 0, 3, 7, 14 | 
| Efficacy - Viral antigens | Viral antigens evaluated: influenza A and B, respiratory syncytial virus, adenovirus, parainfluenza virus. Virus antigens were isolated from nasal swabs and detected by using validated immunofluorescence testing methods. Efficacy assessment: evaluate viral antigen levels at the end of treatment (Day 7) versus the baseline data (Day 0) and compare with the placebo group. | Day 0, 3, 7 | 
| Safety - Adverse events | Adverse events occurring during the study were recorded daily by the patients into a patient dairy (Day 0 to Day 14). Clinically relevant laboratory parameters changes outside the normal range were also considered as adverse events. The relationship of the adverse events to the intake of the investigational drug assessed by the investigator. | Day 0 to Day 14 | 
| Safety - Laboratory parameters - Immune status | Assessment of the immune status was performed by evaluating the concentration in blood serum of interferon [IFN]-alpha and IFN-gamma, immunoglobulin A, immunoglobulin M, immunoglobulin G. Determination of immunoglobulins А, М, G was performed by turbidimetry. Determination of interferon-alpha and interferon-gamma in human blood serum was carried out using flow cytometer. | Day 0, 7, 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viral infections, Amizon, Enisamium iodide, Influenza