Efficacy and Safety of Enisamium Iodide for the Treatment of Acute Respiratory Viral Infections, Including Influenza.
Primary Purpose
Acute Respiratory Viral Infections, Human Influenza
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Enisamium Iodide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Viral Infections focused on measuring Viral infections, Amizon, Enisamium iodide, Influenza
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group 1 - Active Treatment
Group 2 - Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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).
Efficacy - Body temperature normalization
Monitor body temperature.
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.
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.
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.
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.
Full Information
NCT ID
NCT04682444
First Posted
December 17, 2020
Last Updated
December 22, 2020
Sponsor
Joint Stock Company "Farmak"
1. Study Identification
Unique Protocol Identification Number
NCT04682444
Brief Title
Efficacy and Safety of Enisamium Iodide for the Treatment of Acute Respiratory Viral Infections, Including Influenza.
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
April 13, 2009 (Actual)
Primary Completion Date
January 28, 2010 (Actual)
Study Completion Date
May 15, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Joint Stock Company "Farmak"
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Viral Infections, Human Influenza
Keywords
Viral infections, Amizon, Enisamium iodide, Influenza
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Double (Participant, Outcomes Assessor) Matching placebo tablet.
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1 - Active Treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2 - Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Enisamium Iodide
Other Intervention Name(s)
Amizon
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients ingested placebo tablets after meal without chewing in the dose 0.5 g (2 tablets), 3 times a day, for 7 days.
Primary Outcome Measure Information:
Title
Efficacy - Clinical improvement from Day 3 after therapy start
Description
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).
Time Frame
Day 0, 3, 7, 14
Secondary Outcome Measure Information:
Title
Efficacy - Time of disappearance of respiratory tract affection symptoms
Description
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).
Time Frame
Day 0, 3, 7, 14
Title
Efficacy - Body temperature normalization
Description
Monitor body temperature.
Time Frame
Day 0, 3, 7, 14
Title
Efficacy - General symptoms of ARVI including influenza
Description
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.
Time Frame
Day 0, 3, 7, 14
Title
Efficacy - Viral antigens
Description
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.
Time Frame
Day 0, 3, 7
Title
Safety - Adverse events
Description
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.
Time Frame
Day 0 to Day 14
Title
Safety - Laboratory parameters - Immune status
Description
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.
Time Frame
Day 0, 7, 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ekatarina A. Okhapkina
Organizational Affiliation
Smorodintsev Research Institute of Influenza
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33558285
Citation
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.
Results Reference
derived
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Efficacy and Safety of Enisamium Iodide for the Treatment of Acute Respiratory Viral Infections, Including Influenza.
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