Trial Outcomes & Findings for Efficacy of Anaferon for Children in the Treatment of Influenza and Acute Respiratory Viral Infections in Children (NCT NCT02072174)

NCT ID: NCT02072174

Last Updated: 2019-07-12

Results Overview

Disease duration is assessed until recovery or significant improvement. Average illness duration is defined as the interval between the start of the trial treatment and the start of the first 24-hour period in which the non-specific symptoms and nasal/ throat/ chest symptoms improve to "absent" or "mild" (Total Symptom Score of severity had decreased to ≤2 points) and body temperature returns to 37.2°C or below. Based on patient diary data.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

569 participants

Primary outcome timeframe

From the time of randomization until the time of recovery/improvement (days 1-14)

Results posted on

2019-07-12

Participant Flow

Participant milestones

Participant milestones
Measure	Anaferon for Children Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Overall Study STARTED	290	279
Overall Study COMPLETED	258	240
Overall Study NOT COMPLETED	32	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Anaferon for Children Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Overall Study Did Not Meet In-/Exclusion Criteria	14	15
Overall Study Protocol Violation	16	23
Overall Study Physician Decision	0	1
Overall Study Non-compliance with protocol requirement	2	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Total n=498 Participants Total of all reporting groups
Count of Participants	258 Participants n=258 Participants	240 Participants n=240 Participants	498 Participants n=498 Participants
Age, Continuous	6.8 years STANDARD_DEVIATION 2.7 • n=258 Participants	6.7 years STANDARD_DEVIATION 2.7 • n=240 Participants	6.7 years STANDARD_DEVIATION 2.7 • n=498 Participants
Sex: Female, Male Female	118 Participants n=258 Participants	115 Participants n=240 Participants	233 Participants n=498 Participants
Sex: Female, Male Male	140 Participants n=258 Participants	125 Participants n=240 Participants	265 Participants n=498 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From the time of randomization until the time of recovery/improvement (days 1-14)

Population: Per Protocol set

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Average Illness Duration	4.6 days Standard Deviation 1.4	4.9 days Standard Deviation 1.3

SECONDARY outcome

Timeframe: on days 2, 3, 4 and 5 of the treatment

Population: Per Protocol set

Based on Days 2, 3, 4 and 5 of observation treatment (according to the patient's diary), on days 3 and 5 of therapy (according to physician's objective examination).

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Percentage of Patients With Recovery/Improvement in Health Day 3 (physician's examination)	31 Participants	16 Participants
Percentage of Patients With Recovery/Improvement in Health Day 5 (physician's examination)	116 Participants	90 Participants
Percentage of Patients With Recovery/Improvement in Health Day 2 (patient diary data)	1 Participants	1 Participants
Percentage of Patients With Recovery/Improvement in Health Day 3 (patient diary data)	25 Participants	11 Participants
Percentage of Patients With Recovery/Improvement in Health Day 4 (patient diary data)	61 Participants	40 Participants
Percentage of Patients With Recovery/Improvement in Health Day 5 (patient diary data)	107 Participants	84 Participants

SECONDARY outcome

Timeframe: baseline and days 2, 3, 4 and 5 of observation treatment

Population: Per Protocol set

Changes in Body Temperature Based on Patient Diary Data

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Changes in Body Temperature Day 1	38.5 °C Standard Deviation 0.4	38.5 °C Standard Deviation 0.4
Changes in Body Temperature Day 2	38.0 °C Standard Deviation 0.8	38.2 °C Standard Deviation 0.8
Changes in Body Temperature Day 3	37.4 °C Standard Deviation 0.8	37.5 °C Standard Deviation 0.8
Changes in Body Temperature Day 4	37.0 °C Standard Deviation 0.6	37.1 °C Standard Deviation 0.7
Changes in Body Temperature Day 5	36.8 °C Standard Deviation 0.4	36.9 °C Standard Deviation 0.4

SECONDARY outcome

Timeframe: on days 2, 3, 4 and 5 of observation treatment

Population: Per Protocol set

Based on the patient diary data. Axillary temperature (morning and evening) decline to or below 37.0 ºС.

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Percentage of Patients With Normal Body Temperature (≤37.0ºС) Day 2 (patient diary data)	31 Participants	23 Participants
Percentage of Patients With Normal Body Temperature (≤37.0ºС) Day 3 (patient diary data)	104 Participants	76 Participants
Percentage of Patients With Normal Body Temperature (≤37.0ºС) Day 4 (patient diary data)	167 Participants	139 Participants
Percentage of Patients With Normal Body Temperature (≤37.0ºС) Day 5 (patient diary data)	219 Participants	196 Participants

SECONDARY outcome

Timeframe: on days 2-6 of observation treatment

Population: Per Protocol set

Total Symptom Score is based on the severity of each Influenza / Acute Respiratory Viral Infection symptom. Total Symptom Score includes 13 symptoms: body temperature, non-specific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), nasal/throat/chest symptoms. The severity of non-specific and nasal/throat/chest symptom is scored on a symptom severity scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). Minimum score=0; maximum score=39. The severity of symptoms is recorded by the doctors on the case record form on days 3, 5 and by parents/adopter on a diary card twice a day on days 2-6.

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score. Day 5 (patient diary data)	3.3 score on a scale Standard Deviation 2.9	3.8 score on a scale Standard Deviation 3.1
Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score. Day 4 (patient diary data)	5.0 score on a scale Standard Deviation 3.8	5.5 score on a scale Standard Deviation 3.8
Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score. Day 3 (physician's examination)	7.0 score on a scale Standard Deviation 4.6	8.1 score on a scale Standard Deviation 4.8
Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score. Day 5 (physician's examination)	3.5 score on a scale Standard Deviation 3.0	3.9 score on a scale Standard Deviation 3.0
Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score. Day 2 (patient diary data)	10.0 score on a scale Standard Deviation 5.3	11.0 score on a scale Standard Deviation 5.1
Severity of Clinical Manifestations of Influenza / Acute Respiratory Viral Infection by Total Symptom Score. Day 3 (patient diary data)	7.0 score on a scale Standard Deviation 4.8	8.1 score on a scale Standard Deviation 4.8

SECONDARY outcome

Timeframe: on days 1-7 of observation (based on days 1-7 on the patient diary data; on days 1, 3, 5 and 7 of observation - according to physician's objective examination)

Population: Per Protocol set

Total Symptom Score is based on the severity of each disease symptom. The TSS includes 13 symptoms: body temperature/fever, non-specific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness), nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, sore throat, hoarseness, cough, chest pain/tightness of the chest). Minimum score=0; maximum score=39. The area under the curve 1 = on days 1, 3, 5 and 7 on the results of doctor's examination The area under the curve 2 = based on days 1-7 on the patient diary data

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Assessment of the Severity of Influenza Virus / Acute Respiratory Viral Infection Using the "Area Under the Curve" for an Overall Symptom Assessment Days 1-7 (patient diary data)	34.4 score*day Standard Deviation 18.8	38.2 score*day Standard Deviation 18.5
Assessment of the Severity of Influenza Virus / Acute Respiratory Viral Infection Using the "Area Under the Curve" for an Overall Symptom Assessment Days 1, 3, 5 and 7 (physician's examination)	17.6 score*day Standard Deviation 8.9	19.3 score*day Standard Deviation 8.9

SECONDARY outcome

Timeframe: on days 1-5 of therapy

Population: Per Protocol set

Number of Intakes of Antipyretics based on patient diary data

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Number of Intakes of Antipyretics Day 3	0.3 Number of intakes Standard Deviation 0.6	0.4 Number of intakes Standard Deviation 0.8
Number of Intakes of Antipyretics Day 1	1.2 Number of intakes Standard Deviation 0.9	1.3 Number of intakes Standard Deviation 1.0
Number of Intakes of Antipyretics Day 2	0.7 Number of intakes Standard Deviation 1.0	0.9 Number of intakes Standard Deviation 1.1
Number of Intakes of Antipyretics Day 4	0.1 Number of intakes Standard Deviation 0.4	0.1 Number of intakes Standard Deviation 0.5
Number of Intakes of Antipyretics Day 5	0.0 Number of intakes Standard Deviation 0.2	0.1 Number of intakes Standard Deviation 0.4

SECONDARY outcome

Timeframe: on days 1, 3, 5, 7 of observation treatment

Population: Viral load is evaluated in subjects with positive influenza A and B tests.

Viral load is evaluated in subjects with positive influenza A and B tests. Virus load \[log10 copies influenza А/В RNA per 1 mL\] in nasal and pharyngeal swabs is determined using real-time PCR on days 1, 3, 5 and 7.

Outcome measures

Outcome measures
Measure	Anaferon for Children n=49 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=51 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Change in Viral Load During the Treatment and Follow-up Periods Day 1	5.7 log10 copies influenza А/В RNA per 1 mL Standard Deviation 1.1	5.6 log10 copies influenza А/В RNA per 1 mL Standard Deviation 1.3
Change in Viral Load During the Treatment and Follow-up Periods Day 3	4.1 log10 copies influenza А/В RNA per 1 mL Standard Deviation 2.2	4.8 log10 copies influenza А/В RNA per 1 mL Standard Deviation 1.3
Change in Viral Load During the Treatment and Follow-up Periods Day 5	3.1 log10 copies influenza А/В RNA per 1 mL Standard Deviation 2.3	4.4 log10 copies influenza А/В RNA per 1 mL Standard Deviation 1.3
Change in Viral Load During the Treatment and Follow-up Periods Day 7	2.1 log10 copies influenza А/В RNA per 1 mL Standard Deviation 2.4	4.0 log10 copies influenza А/В RNA per 1 mL Standard Deviation 1.5

SECONDARY outcome

Timeframe: 14 days of observation treatment

Population: Per Protocol set

The development of disease complications requiring antibiotics drugs or hospitalization

Outcome measures

Outcome measures
Measure	Anaferon for Children n=258 Participants Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=240 Participants Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Percentage of Patients With Exacerbation of the Disease Course	7 Participants	11 Participants

Adverse Events

Anaferon for Children

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Anaferon for Children n=290 participants at risk Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=279 participants at risk Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Infections and infestations Influenza	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)

Other adverse events

Additional Information

Michael Putilovskiy, MD, PhD, Clinical and Medical Department Director

Materia Medica Holding

Phone: +74952761571

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Anaferon for Children n=290 participants at risk Anaferon for Children: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.	Placebo n=279 participants at risk Placebo: 1 tablet per 1 intake. On the first day of treatment: the first 2 hours of 1 tablet every 30 minutes, then, during the first day, 3 more times at regular intervals. From the second to the fifth day: 1 tablet 3 times a day. The drug is taken out of the reception of food (in the interval between meals or 15-30 minutes before eating), should be kept in your mouth, not swallowed, until it is dissolved completely.
Gastrointestinal disorders Abdominal pain	1.0% 3/290 • Number of events 3 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Adenoiditis	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.00% 0/279 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Bacterial infection	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Bronchitis	1.0% 3/290 • Number of events 3 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	1.4% 4/279 • Number of events 4 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Conjunctivitis	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	1.1% 3/279 • Number of events 3 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Congenital, familial and genetic disorders Cryptorchism	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Gastrointestinal disorders Diarrhoea	0.69% 2/290 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Nervous system disorders Dizziness	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Nervous system disorders Dizziness postural	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.00% 0/279 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Gastrointestinal disorders Dysbacteriosis	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Gastrointestinal disorders Enteritis	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Respiratory, thoracic and mediastinal disorders Epistaxis	1.0% 3/290 • Number of events 4 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.00% 0/279 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Immune system disorders Hypersensitivity	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Infection	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Gastrointestinal disorders Inguinal hernia	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Nasopharyngitis	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Gastrointestinal disorders Nausea	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 3 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Otitis media acute	1.4% 4/290 • Number of events 4 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	1.8% 5/279 • Number of events 5 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Otosalpingitis	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Skin and subcutaneous tissue disorders Petechiae	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.00% 0/279 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Pharyngotonsillitis	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Nervous system disorders Polyneuropathy	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.00% 0/279 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
General disorders Fever	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.00% 0/279 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Rhinitis	1.0% 3/290 • Number of events 3 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Sinusitis	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Superinfection bacterial	0.34% 1/290 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.00% 0/279 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Tonsillitis	0.69% 2/290 • Number of events 2 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Tonsillitis bacterial	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Tracheobronchitis	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Infections and infestations Viral rash	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.36% 1/279 • Number of events 1 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)
Gastrointestinal disorders Vomiting	0.00% 0/290 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)	0.72% 2/279 • Number of events 3 • Adverse/Serious adverse events were registered during 14 days (during the treatment and follow-up periods ). Adverse/Serious adverse events were registered in patients of the Safety population (n=569)