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

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.

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).

Study Overview

• Status: Completed
• Conditions: Human Influenza; Acute Respiratory Viral Infections
• Intervention / Treatment: Drug: Enisamium Iodide; Drug: Placebo

Detailed Description

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 immunoglobulin (Ig) A, M, and G (IgA, IgM, and IgG).

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - Active Treatment - Amizon; Patient who were randomized into Group 1 ingested Amizon tablets 500 mg (as 2 tablets, each tablet containing 250 mg enisamium iodide) after a meal, 3 times a day, for 7 days.	Drug: Enisamium Iodide; Patients ingested Amizon tablets without chewing, after meal, as follows: 2 tablets (total dose 500 mg) 3 times a day, for 7 days. Each tablet contains 250 mg of Nmethyl-4-N-methyl-4-benzylcarbamidopyridinium iodide (INN enisamium iodide).; Other Names: Amizon
Placebo Comparator: Group 2 - Placebo; Patient who were randomized into Group 2 ingested placebo tablets 500 mg (2 tablets), after a meal 3 times a day, for 7 days.	Drug: Placebo; Patients ingested placebo tablets without chewing, after meal, in the dose 500 mg (2 tablets), 3 times a day, for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Number of Participants -- Absence of Objective Symptoms -- Overall	Count of participants WITHOUT objective symptoms -- overall. Objective symptoms of acute respiratory viral infection (ARVI), including influenza, were monitored: fever, pharyngeal hyperemia, rhinitis, arterial blood pressure, enlarged lymph nodes, auscultation findings for lung and heart. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza. A score system used to assess participants' health. A higher score implies worse outcome. Objective symptoms scores were: normal or abnormal blood pressure: 0 or 4 score points; lung auscultation: 0 points; vesicular breath sound and wheezing or crepitation 2 or 4 points, respectively; clear and rhythmic heart sounds -- each 0 points; noisy and arrhythmic heart sounds -- each 2 score points.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Days Without Routine Activities -- Summary	Count of participants who had days WITHOUT routine activities. Disability to perform routine tasks and activities were reported by the participants to the investigator at each study visit.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Viral Antigens -- Overall	Viral antigens that were evaluated: adenovirus, corona virus, influenza A, influenza B, parainfluenza virus, respiratory syncytial virus. Virus antigens were isolated from nasal swabs and detected by using validated immunofluorescence staining methods. Efficacy assessment was based on the determination of viral antigen on treatment days (Day 3 and Day 7) compared with the baseline (Day 0) in the active treatment group and the placebo group. Results represent the count of participants who did NOT have detectable viral antigens.	Day 0 (baseline), 3, 7.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Number of Participants -- Absence of Subjective Symptoms -- Overall	Count of participants WITHOUT overall subjective symptoms. Subjective symptoms of acute respiratory viral infection (ARVI) including influenza, that were monitored: elevated body temperature, chills, cough, headache, myalgia, sore throat, weakness. Evaluate the number of participants in the treatment and the placebo groups without the subjective symptoms from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of ARVI, including influenza. The subjective symptoms were assessed using a 4-point Likert scale, ranging from score 1 (absent symptoms ) to score 4 (severe symptoms).	Day 0 (baseline), 3, 7, 14.
Efficacy: Subjective Symptom Sum Score (4-point Likert Scale)	Subjective symptom sum score. Subjective symptoms of acute respiratory viral infection (ARVI) including influenza, that were monitored: elevated body temperature, chills, cough, headache, myalgia, sore throat, weakness. The subjective symptoms were assessed using a 4-point Likert scale for the individual assessment of the severity of the above 7 symptoms, ranging from absent (0), mild (1), moderate (2), or severe (3). A higher score implies worse outcome.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Subjective Symptom -- Chills	Chills. Count of participants WITHOUT the subjective symptom: chills. Evaluate the number of participants in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Subjective Symptom -- Cough	Cough. Count of participants WITHOUT the subjective symptom: cough. Evaluate the number of participants in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Subjective Symptom -- Elevated Body Temperature	Count of participants WITHOUT perceived elevated body temperature. Evaluate the number of patients in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Subjective Symptom -- Sore Throat	Subjective symptoms. Count of participants WITHOUT the subjective symptom: sore throat. Evaluate the number of patients in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Subjective Symptom -- Headache	Subjective symptoms. Count of participants WITHOUT the subjective symptom: headache. Evaluate the number of patients in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Subjective Symptom -- Myalgia	Myalgia. Count of participants WITHOUT the subjective symptom: myalgia. Evaluate the number of participants in the active treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Subjective Symptom -- Weakness	Subjective symptoms. Count of participants WITHOUT the subjective symptom: weakness. Evaluate the number of participants in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, relating to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Objective Symptom -- Body Temperature	Efficacy: Count of participants WITHOUT objective symptom: Body temperature. Evaluate the number of patients in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. A score system was used to assess patient health, as described under endpoint #1.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Objective Symptom: Body Temperature -- Body Temperature Ranges	Body temperature. Count of participants in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Clinical improvement was assessed by the investigator, with respect to the severity of clinical symptoms of acute respiratory viral infection (ARVI), including influenza.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Objective Symptom -- Lungs Auscultation	Efficacy: Count of participants WITHOUT objective symptom: Lungs auscultation (abnormal breath sounds, detected using a stethoscope). Evaluate the number of patients in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. A score system was used to assess patient health, as described under endpoint #1.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Absence of Objective Symptom -- Pharyngeal Hyperemia	Efficacy: Number of participants WITHOUT objective Symptom: Pharyngeal Hyperemia. Evaluate the number of participants in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. A score system was used to assess patient health, as described under endpoint #1.	Day 0 (baseline), 3, 7, 14.
Efficacy Objective Symptom: Number of Participants -- Pharyngeal Hyperemia -- Severity	Pharyngeal hyperemia. Count of participants in the treatment and the placebo groups regarding clinical status from Day 3 after therapy start. Severity was assessed by the investigator, using a 4-point score scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe.	Day 0 (baseline), 3, 7, 14.
Efficacy: Objective Clinical Sum Score	Objective clinical sum score. Objective symptoms of acute respiratory viral infection (ARVI), were monitored. For the objective clinical sum score, clinical status was assessed by the investigator, relating to the severity of clinical symptoms of ARVI, including influenza. A score system (score points) that was used to assess participants' health, was based on objective symptoms scores, shown below.; Blood pressure: normal=0 points; abnormal=4 points.; Lung auscultation: vesicular breath sound=0 points; wheezing=2 points; crepitation=4 points.; Heart sound; clear heart sounds=0 points; rhythmic heart sounds=0 points; noisy heart sounds=2 points; arrhythmic heart sounds=2 points. A higher score implies worse clinical outcome.	Day 0 (baseline), 3, 7, 14.
Efficacy: Number of Participants -- Viral Antigens -- Baseline Status	Count of randomised participants and their viral antigen types at baseline. Viral antigens evaluated: adenovirus, corona virus, influenza A (and subtypes), influenza B, parainfluenza virus, respiratory syncytial virus. Virus antigens were isolated from nasal swabs and detected by using validated immunofluorescence staining methods.	Day 0 (baseline).
Efficacy: Number of Participants -- Viral Antigen -- Influenza Type A	Count of participants who did NOT have a detectable viral antigen -- influenza Type A Virus antigen was isolated from nasal swabs and detected by using validated immunofluorescence staining methods. Efficacy assessment was the determination of viral antigen on treatment days (Day 3 and Day 7) compared with the baseline (Day 0) in the active treatment group and the placebo group.	Day 0 (baseline), 3, 7.
Efficacy: Number of Participants -- Viral Antigen -- Influenza Type A or Type B	Viral antigen: Count of participants who did NOT have detectable viral antigen -- influenza Type A or Type B. Virus antigen was isolated from nasal swabs and detected by using validated immunofluorescence staining methods. Efficacy assessment was the determination of viral antigen on treatment days (Day 3 and Day 7) compared with the baseline (Day 0) in the active treatment group and the placebo group.	Day 0 (baseline), 3, 7.
Efficacy: Number of Participants -- Viral Antigen -- Influenza Type B	Viral antigen: Number of participants who did NOT have detectable viral antigen -- influenza Type B. Virus antigen was isolated from nasal swabs and detected by using validated immunofluorescence staining methods. Efficacy assessment was the determination of viral antigen on treatment days (Day 3 and Day 7) compared with the baseline (Day 0) in the active treatment group and the placebo group.	Day 0 (baseline), 3, 7.
Efficacy: Number of Participants -- Viral Antigen -- Adenovirus	Viral antigen: Count of participants who did NOT have detectable viral antigen -- Adenovirus. Virus antigen was isolated from nasal swabs and detected by using validated immunofluorescence staining methods. Efficacy assessment was the determination of viral antigen on treatment days (Day 3 and Day 7) compared with the baseline (Day 0) in the active treatment group and the placebo group.	Day 0 (baseline), 3, 7.
Efficacy: Number of Participants -- Viral Antigen -- Viral Antigen Combination	Viral antigen: Count of participants who did NOT have detectable viral antigen -- viral antigen combination. Virus antigens were isolated from nasal swabs and detected by using validated immunofluorescence staining methods. Efficacy assessment was the determination of viral antigen on treatment days (Day 3 and Day 7) compared with the baseline (Day 0) in the active treatment group and the placebo group.	Day 0 (baseline), 3, 7.
Safety - Laboratory Parameters - Immune Status -- Immunoglobulin A, M, G	Assessment of the immune status was performed by evaluating the concentration in blood serum of immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG). Determination of IgA, IgM, and IgG was performed by turbidimetry.	Day 0 (baseline), 7, 14.
Safety - Laboratory Parameters -- Immune Status -- Interferon Alpha (IFN-alpha), Interferon Gamma (IFN-gamma)	Assessment of the immune status was performed by evaluating the concentration in blood serum of IFN-alpha and IFN-gamma. Determination of interferon alpha (INF-alpha) and interferon gamma (INF-gamma) in human blood serum was carried out using flow cytometer.	Day 0 (baseline), 7, 14.
Evaluation Health Status: Number of Participants -- Overall Treatment Efficacy (Assessment by Investigator and by Patient)	Overall treatment efficacy. Evaluate the overall efficacy of the treatment by the investigator and by the participants. Results show the number of participants for each assessed category of the health status.	Day 3, 7, 14.

Collaborators and Investigators

• Sponsor: Joint Stock Company "Farmak"
• Investigators: Principal Investigator: Ekatarina A. Okhapkina, Smorodintsev Research Institute of Influenza

Publications and helpful links

General Publications

• Te Velthuis AJW, Zubkova TG, Shaw M, Mehle A, Boltz D, Gmeinwieser N, Stammer H, Milde J, Muller L, Margitich V. Enisamium Reduces Influenza Virus Shedding and Improves Patient Recovery by Inhibiting Viral RNA Polymerase Activity. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02605-20. doi: 10.1128/AAC.02605-20. Print 2021 Mar 18.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2009
• Primary Completion (Actual): January 15, 2010
• Study Completion (Actual): January 15, 2010

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 22, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Influenza; Viral infections; Amizon; Enisamium iodide
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Diseases; Influenza, Human; Virus Diseases; enisamium iodide
• Other Study ID Numbers: AM-STP-2-2008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No