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Clinical Trial Results:
Efficacy, safety and tolerability of Influcid tablets in patients (1 to 65 years old) suffering from upper respiratory tract infections with flu-like symptoms. A randomized, international, multicenter, controlled clinical trial.

Summary
EudraCT number	2010-021422-35
Trial protocol	DE
Global end of trial date	02 Aug 2011

Results information
Results version number	v1(current)
This version publication date	05 Jul 2016
First version publication date	02 Aug 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

09-NI-EP-001

ISRCTN number

ISRCTN60440500

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Deutsche Homöopathie-Union, DHU-Arzneimittel GmbH & Co. KG

Sponsor organisation address

Ottostraße 24, Karlsruhe, Germany, D-76227

Public contact

Deutsche Homöopathie-Union, DHU-Arzneimittel GmbH & Co. KG, Ottostrasse 24, D-76227 Karlsruhe, + 49 (0)721 409301, info@dhu.com

Scientific contact

Deutsche Homöopathie-Union, DHU-Arzneimittel GmbH & Co. KG, Ottostrasse 24, D-76227 Karlsruhe , + 49 (0)721 409301, info@dhu.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

02 Aug 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Aug 2011

Was the trial ended prematurely?

Main objective of the trial

The actual study has been set up to evaluate systematically the efficacy and tolerability of Influcid. Patients received standard symptomatic medication, which was taken on demand (ST group) or Influcid for 7 days in addition to the same on demand symptomatic treatment (IFC group). Response at day 4, defined as absence of fever and absence or very mild degree of upper respiratory tract infection symptoms, was the primary outcome measure.

Protection of trial subjects

All patients received standard symptomatic medication on demand. One half of the patients received additionally Influcid. Examinations performed consisted mainly of a physical examination including evaluation of upper respiratory tract infection complaints and the assessment of upper respiratory tract infection symptoms via a questionnaire. Apart from this questionnaire, physical examination did not differ significantly from routine physical examination, neither did it involve any particular risk for the patient. At inclusion a throat swab (for a group A beta-hemolytic streptococci rapid test) and a nasopharyngeal swab (for an influenza test) were taken. Patients were informed about a possible slight discomfort caused by these tests via the patient informed consent form.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Nov 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Ukraine: 300

Country: Number of subjects enrolled

Germany: 223

Worldwide total number of subjects

523

EEA total number of subjects

223

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

240

Adolescents (12-17 years)

Adults (18-64 years)

219

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Patients were recruited during one cold season going from end of November 2010 until beginning of April 2011. In Ukraine, patients were recruited at 4 general practitioner sites and 8 pediatric sites located mostly in polyclinics. In Germany, patients were recruited at 4 general practitioners practices and 6 pediatric practices.

Screening details

A total of 533 patients gave their informed consent to participate in the trial. 10 of these 533 patients were screening failures due to a postive rapid test for group A beta-hemolytic streptococci at enrolment. A total of 523 patients were randomised.

Period 1 title

overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

ST [SAF]

Arm description

The control group "ST" was treated only with symptomatic medication on-demand.

Arm type

Active comparator

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

IMP N° PR02

Other name

ben-u-ron®

Pharmaceutical forms

Syrup

Routes of administration

Oral use

Dosage and administration details

ben-u-ron® syrup [IMP N° PR02] was offered to all patients of both arms. 5 ml syrup contained 200 mg paracetamol. The prescribed dosage of paracetamol was dependent on age and body weight. Generally 10-15 mg paracetamol per kg body weight as individual dose, up to 60 mg / kg body weight as total daily dose were recommended. The respective dose interval was dependent on symptoms and maximum daily dose, and was not to fall below 6 hours.

Investigational medicinal product name

Oxymetazoline hydrochloride 0.05%

Investigational medicinal product code

IMP N° PR04

Other name

Nasivin®

Pharmaceutical forms

Nasal spray

Routes of administration

Nasal use

Dosage and administration details

Nasivin® syrup [IMP N° PR04] was offered to patients aged 6 years or older of both arms. 1 spray squirt with 45 µl solution contained 22.5 µg of oxymetazoline hydrochloride. The solution was to be squirted 2-3 times per day into every nostril. The individual dose was not to be administered more than 3 times per day. The spray was not to be used for more than 7 days.

Investigational medicinal product name

Oxymetazoline hydrochloride 0.025%

Investigational medicinal product code

IMP N° PR05

Other name

Nasivin®

Pharmaceutical forms

Nasal spray

Routes of administration

Nasal use

Dosage and administration details

Nasivin® syrup [IMP N° PR05] was offered to patients aged 1-5 years or older of both arms. 1 spray squirt with 45 µl solution contained 11.25 µg of oxymetazoline hydrochloride. The solution was to be squirted 2-3 times per day into every nostril. The individual dose was not to be administered more than 3 times per day. The spray was not to be used for more than 7 days.

Investigational medicinal product name

Ambroxol hydrochloride

Investigational medicinal product code

IMP N° PR03

Other name

Mucosolvan®

Pharmaceutical forms

Syrup

Routes of administration

Oral use

Dosage and administration details

Mucosolvan® syrup [IMP N° PR03] was offered to all patients of both arms. 5 ml syrup contained 30 mg ambroxol hydrochloride. Children up to 2 years old were to take 1.25 ml of syrup twice a day. For this age group, the syrup was only to be given according to the direction of the investigator. Children from 2 to 5 years were to take 1.25 ml of syrup three times a day. Children from 6 to 12 years were to take 2.5 ml of syrup 2-3 times a day. Adults and adolescents of 12 years and old were to take 5 ml of syrup 3 times a day during the first 2-3 days, thereafter 5 ml solution twice a day. When dosing for adults - adolescents, an increase of efficacy could be achieved by giving 10 ml of syrup twice a day.

IFC [SAF]

Arm description

The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment

Arm type

Experimental

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

IMP N° PR02

Other name

ben-u-ron®

Pharmaceutical forms

Syrup

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Ambroxol hydrochloride

Investigational medicinal product code

IMP N° PR03

Other name

Mucosolvan®

Pharmaceutical forms

Syrup

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Aconitum D3, Bryonia D2, Eupatorium perfoliatum D1, Gelsemium D3, Ipecacuanha D3 and Phosphorus D5

Investigational medicinal product code

IMP N° PR01

Other name

Influcid®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Test drug was provided to patients of IFC arm only . Separate blisters for children ( <12 years) and adolescents, adults (≥12 years) were provided. Acute dosage (first 72 hours) comprised intake of 1 tablet every 2 hours (8 tablets per day) for children and 1 tablet every hour (12 tablets per day) for adolescents, adults. Maintenance dosage (following 96 hours) comprised intake of 1 tablet 3 times a day (3 tablets per day) for children and 2 tablets 3 times a day (6 tablets per day) for adolescents, adults. [Note: Patients, who were randomised until noon at baseline, took the complete acute dosage on study days 1-3 and started with the maintenance dosage on study day 4. Patients, who were randomised at baseline after noon, took half of the acute dosage on study day 1. These patients took the complete acute dosage on study days 2-4 and started with the maintenance dosage on study day 5.]

Investigational medicinal product name

Oxymetazoline hydrochloride 0.05%

Investigational medicinal product code

IMP N° PR04

Other name

Nasivin®

Pharmaceutical forms

Nasal spray

Routes of administration

Nasal use

Dosage and administration details

Investigational medicinal product name

Oxymetazoline hydrochloride 0.025%

Investigational medicinal product code

IMP N° PR05

Other name

Nasivin®

Pharmaceutical forms

Nasal spray

Routes of administration

Nasal use

Dosage and administration details

Number of subjects in period 1	ST [SAF]	IFC [SAF]
Started	258	265
1st FU visit completed (day 4±1)	258	264
Termination visit completed (day 15±2)	246	256
2nd FU visit completed (day 8±1)	256	262
Completed	246	256
Not completed	12	9
Non compliance/Parents incompliance	-	2
Lost to follow-up	1	1
Protocol deviation	11	5
Lack of efficacy	-	1

Baseline characteristics

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Reporting group title

ST [SAF]

Reporting group description

The control group "ST" was treated only with symptomatic medication on-demand.

Reporting group title

IFC [SAF]

Reporting group description

The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment

Reporting group values	ST [SAF]	IFC [SAF]	Total
Number of subjects	258	265	523
Age categorical
Units: Subjects
< 12 years	133	131	264
≥ 12 years	125	134	259
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	10 (5 to 32)	12 (5 to 33)	-
Gender categorical
Units: Subjects
Male	120	106	226
Female	138	159	297
Influenza A and B test results
Units: Subjects
Influenza A and B negative	219	229	448
Influenza A positive	33	21	54
Influenza B positive	6	12	18
Not recorded	0	3	3
Fever
Assessment of axillary measurement of body temperature [°C] at physicians office.
Units: Subjects
no ( ≤37.2°C)	2	0	2
mild (>37.2°C but <37.5°C)	0	0	0
moderate (≥37.5°C but <38.5°C)	224	226	450
high ( ≥38.5°C)	32	39	71
Presence of hyperemia of mucosa
Units: Subjects
no	28	24	52
yes	230	241	471
Presence of nasal breathing impairment
Units: Subjects
no	27	38	65
yes	231	227	458
Ability to perform daily activities
Units: Subjects
no	211	198	409
yes	47	67	114
Presence of nasal symptoms [URTI symptom 1]
Units: Subjects
no	16	30	46
yes	242	235	477
Presence of Pharyngeal symptoms [URTI symptom 2]
Units: Subjects
no	24	21	45
yes	234	244	478
Presence of Cough [URTI symptom 3]
Units: Subjects
no	48	67	115
yes	210	198	408
Presence of Feeling tired [URTI symptom 4]
Units: Subjects
no	7	4	11
yes	251	261	512
Presence of Weakness [URTI symptom 5]
Units: Subjects
no	8	9	17
yes	250	256	506
Presence of Body aches [URTI symptom 6]
Units: Subjects
no	50	53	103
yes	208	212	420
Presence of Irritable/whiny [URTI symptom 7]
This symptom has been assessed for chidren [patients <12 years] only.
Units: Subjects
no	17	16	33
yes	116	115	231
Not applicable [patients >12 years]	125	134	259
Presence of Less active [URTI symptom 8]
This symptom has been assessed for chidren [patients <12 years] only.
Units: Subjects
no	5	5	10
yes	128	126	254
Not applicable [patients >12 years]	125	134	259
Body temperature
Axillary measurement of body temperature [°C] at physicians office.
Units: [°C]
median (inter-quartile range (Q1-Q3))	37.9 (37.8 to 38.2)	37.9 (37.8 to 38.2)	-
WURSS-21 total sum score
The WURSS-21 total sum score is calculated as sum of items 2 to 20 of the Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21) which is a 21-item illness-specific health-related quality of life questionnaire. [Note: Available diary WURSS-21 questionnaire data at baseline was recorded for: N=230 (ST [SAF]); N=240 (IFC [SAF]); N=208 (ST arm [PP analysis set]); N=230 (ST arm [ITT analysis set]); N=238 (IFC arm [ITT analysis set]) and N=209 (IFC arm [PP analysis set]) patients.]
Units: SCORE
median (inter-quartile range (Q1-Q3))	75 (59 to 92)	72 (53 to 92.5)	-

Subject analysis set title

ST arm [ITT analysis set]

Subject analysis set type

Intention-to-treat

Subject analysis set description

This subject analysis set consists of all patients of ST arm who contributed post-baseline efficacy data. N=2 out of N=258 ST patients have been excluded from 'ST arm [ITT analysis set]' due to missing post-baseline efficacy data.

Subject analysis set title

ST arm [PP analysis set]

Subject analysis set type

Per protocol

Subject analysis set description

This subject analysis set consists of all patients of ST arm without major protocol violations. N=37 out of N=258 ST patients have been excluded from 'ST arm [PP analysis set]' due to relevant protocol violations.

Subject analysis set title

IFC arm [PP analysis set]

Subject analysis set type

Per protocol

Subject analysis set description

This subject analysis set consists of all patients of IFC arm without major protocol violations. N=41 out of N=265 IFC patients have been excluded from 'IFC arm [PP analysis set]' due to relevant protocol violations.

Subject analysis set title

IFC arm [ITT analysis set]

Subject analysis set type

Intention-to-treat

Subject analysis set description

This subject analysis set consists of all patients of IFC arm who contributed post-baseline efficacy data. N=4 out of N=265 IFC patients have been excluded from 'IFC arm [ITT analysis set]' due to missing post-baseline efficacy data.

Subject analysis sets values	ST arm [ITT analysis set]	ST arm [PP analysis set]	IFC arm [PP analysis set]	IFC arm [ITT analysis set]
Number of subjects	256	221	224	261
Age categorical
Units: Subjects
< 12 years	131	110	117	130
≥ 12 years	125	111	107	131
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	10.5 (5 to 32.5)	12 (5 to 33)	10 (4 to 33)	12 (4 to 33)
Gender categorical
Units: Subjects
Male	118	102	88	104
Female	138	119	136	157
Influenza A and B test results
Units: Subjects
Influenza A and B negative	219	196	198	227
Influenza A positive	31	20	12	19
Influenza B positive	6	5	11	12
Not recorded	0	0	3	3
Fever
Assessment of axillary measurement of body temperature [°C] at physicians office.
Units: Subjects
no ( ≤37.2°C)	2	0	0	0
mild (>37.2°C but <37.5°C)	0	0	0	0
moderate (≥37.5°C but <38.5°C)	222	195	191	222
high ( ≥38.5°C)	32	26	33	39
Presence of hyperemia of mucosa
Units: Subjects
no	28	18	23	24
yes	228	203	201	237
Presence of nasal breathing impairment
Units: Subjects
no	27	24	36	38
yes	229	197	188	223
Ability to perform daily activities
Units: Subjects
no	209	182	172	196
yes	47	39	52	65
Presence of nasal symptoms [URTI symptom 1]
Units: Subjects
no	16	14	29	30
yes	240	207	195	231
Presence of Pharyngeal symptoms [URTI symptom 2]
Units: Subjects
no	24	17	19	21
yes	232	204	205	240
Presence of Cough [URTI symptom 3]
Units: Subjects
no	48	44	60	67
yes	208	177	164	194
Presence of Feeling tired [URTI symptom 4]
Units: Subjects
no	7	7	3	4
yes	249	214	221	257
Presence of Weakness [URTI symptom 5]
Units: Subjects
no	8	7	8	9
yes	248	214	216	252
Presence of Body aches [URTI symptom 6]
Units: Subjects
no	48	37	45	53
yes	208	184	179	208
Presence of Irritable/whiny [URTI symptom 7]
This symptom has been assessed for chidren [patients <12 years] only.
Units: Subjects
no	17	11	14	16
yes	114	99	103	114
Not applicable [patients >12 years]	125	111	107	131
Presence of Less active [URTI symptom 8]
This symptom has been assessed for chidren [patients <12 years] only.
Units: Subjects
no	5	3	5	5
yes	126	107	112	125
Not applicable [patients >12 years]	125	111	107	131
Body temperature
Axillary measurement of body temperature [°C] at physicians office.
Units: [°C]
median (inter-quartile range (Q1-Q3))	37.9 (37.8 to 38.2)	37.9 (37.8 to 38.2)	37.9 (37.8 to 38.2)	37.9 (37.8 to 38.2)
WURSS-21 total sum score
The WURSS-21 total sum score is calculated as sum of items 2 to 20 of the Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21) which is a 21-item illness-specific health-related quality of life questionnaire. [Note: Available diary WURSS-21 questionnaire data at baseline was recorded for: N=230 (ST [SAF]); N=240 (IFC [SAF]); N=208 (ST arm [PP analysis set]); N=230 (ST arm [ITT analysis set]); N=238 (IFC arm [ITT analysis set]) and N=209 (IFC arm [PP analysis set]) patients.]
Units: SCORE
median (inter-quartile range (Q1-Q3))	75 (59 to 92)	77 (60 to 93.5)	70 (54 to 92)	72 (54 to 93)

End points

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Reporting group title

ST [SAF]

Reporting group description

The control group "ST" was treated only with symptomatic medication on-demand.

Reporting group title

IFC [SAF]

Reporting group description

The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment

Subject analysis set title

ST arm [ITT analysis set]

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

ST arm [PP analysis set]

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

IFC arm [PP analysis set]

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

IFC arm [ITT analysis set]

Subject analysis set type

Intention-to-treat

Subject analysis set description

Primary: Fraction of patients with symptom alleviation at day 4 of the study

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End point title

Fraction of patients with symptom alleviation at day 4 of the study

End point description

Symptoms alleviation is defined as: - Absence of fever (axillary temperature ≤ 37.2°C) and - Absence or very mild degree of the symptoms assessed by Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21) which is a 21-item illness-specific health-related quality of life questionnaire. Fever was measured 3-times daily by the patient (or in case of children by their parents) at home. Mean value covering last 24 hours was basis for this definition. Absence or very mild degree of symptoms is defined as answer to question “How sick do you feel today?” with “0” (not sick) or “1” (very mildly) for both assessments at day 4 (WURSS-21 was filled in twice daily by the patient or in case of children by their parents at home).

End point type

Primary

End point timeframe

Study day 4

End point values	IFC arm [PP analysis set]	ST arm [PP analysis set]	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	224	221	252 ^[1]	259 ^[2]
Units: Patients
No	191	209	235	219
Yes	33	12	17	40

Notes
[1] - 4 out of 256 ST arm [ITT analysis set] patients were excluded from due to invalid diary data.
[2] - 2 out of 261 IFC arm [ITT analysis set] patients were excluded from due to invalid diary data.

Test for equality of fractions between arms [PP]

Statistical analysis description

Explorative analysis of upper respiratory tract infection [URTI] symptom alleviation at day 4. Categorization of symptom alleviation at day 4 ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [PP analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0011 ^[3]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

9.3

Confidence interval

level

95%

sides

2-sided

lower limit

3.33

upper limit

15.27

Notes
[3] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 4 in IFC compared to ST arm [PP analysis set].

Test for equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of URTI symptom alleviation at day 4. Categorization of symptom alleviation at day 4 ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.

Comparison groups

IFC arm [ITT analysis set] v ST arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0018 ^[4]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

8.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.93

upper limit

14.47

Notes
[4] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 4 in IFC compared to ST arm [ITT analysis set].

Secondary: Time to symptom alleviation

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End point title

Time to symptom alleviation

End point description

The first day a patient had rated item 1 of WURSS-21 (“How sick do you feel today”) not higher than 1 (=”very mildly sick”) for both morning and evening assessments was used for evaluating the time to symptom alleviation. Only patients with valid diary data and WURSS-21 item 1 assessed at baseline were considered. Symptom had to be present at baseline, i.e. assessment of WURSS-21 item 1 (if available) at baseline visit had to be scored with value ">1". Finally, only patients who who had a symptom alleviation until study day 14 could be taken into account for this analysis.

End point type

Secondary

End point timeframe

Study day 2 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	215 ^[5]	236 ^[6]
Units: [days]
median (inter-quartile range (Q1-Q3))	8 (7 to 10)	7 (5 to 8)

Notes
[5] - 41 out of 256 ST arm [ITT analysis set] patients were excluded due to missing data.
[6] - 25 out of 261 IFC arm [ITT analysis set] patients were excluded due to missing data.

Time to symptom alleviation [ITT]

Statistical analysis description

Explorative analysis of time to symptom alleviation. Time to symptom alleviation [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom alleviation between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

451

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[7]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[7] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom alleviation [days] in IFC compared to ST arm [ITT analysis set].

Secondary: Fraction of patients with symptom alleviation as defined for primary objective at study day 2, 3, 5, etc. until end of study

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End point title

Fraction of patients with symptom alleviation as defined for primary objective at study day 2, 3, 5, etc. until end of study

End point description

Presented counts refer to the number of patients per study day with observed symptom alleviation. Symptoms alleviation is defined as: - Absence of fever (axillary temperature ≤ 37.2°C) and - Absence or very mild degree of the symptoms assessed by Wisconsin Upper Respiratory Symptom Survey 21 (WURSS-21). Fever was measured 3-times daily by the patient (or in case of children by their parents) at home. Mean value covering last 24 hours was basis for this definition. Absence or very mild degree of symptoms is defined as answer to question “How sick do you feel today?” with “0” (not sick) or “1” (very mildly) for both assessments at corresponding day (WURSS-21 was filled in twice daily by the patient or in case of children by their parents at home).

End point type

Secondary

End point timeframe

study day 2 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	252 ^[8]	259 ^[9]
Units: patients
Day 2	1	2
Day 3	7	15
Day 4	17	40
Day 5	31	76
Day 6	53	111
Day 7	73	150
Day 8	109	178
Day 9	141	194
Day 10	169	204
Day 11	181	212
Day 12	198	219
Day 13	207	227
Day 14	217	230

Attachments

Difference between treatment arms per day

Notes
[8] - 4 out of 256 ST arm [ITT analysis set] patients were excluded from due to invalid diary data.
[9] - 2 out of 261 IFC arm [ITT analysis set] patients were excluded from due to invalid diary data.

Day 2: Equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of URTI symptom alleviation as defined for primary endpoint. Categorization of symptom alleviation ('Response' [Yes/No]) was tested for treatment related differences. Presented values for risk difference are related to the difference in responsive patients between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[10]

P-value

= 0.5787

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

2.1

Notes
[10] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).

Day 3: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.0933

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

6.9

Notes
[11] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).

Day 4: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[12]

P-value

= 0.0018 ^[13]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

8.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.9

upper limit

14.5

Notes
[12] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[13] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 4 in IFC compared to ST arm [ITT analysis set].

Day 5: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[14]

P-value

< 0.0001 ^[15]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

24.3

Notes
[14] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[15] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 5 in IFC compared to ST arm [ITT analysis set].

Day 6: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[16]

P-value

< 0.0001 ^[17]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

21.8

Confidence interval

level

95%

sides

2-sided

lower limit

13.6

upper limit

30.1

Notes
[16] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[17] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 6 in IFC compared to ST arm [ITT analysis set].

Day 7: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[18]

P-value

< 0.0001 ^[19]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

28.9

Confidence interval

level

95%

sides

2-sided

lower limit

20.3

upper limit

37.6

Notes
[18] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[19] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 7 in IFC compared to ST arm [ITT analysis set].

Day 8: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[20]

P-value

< 0.0001 ^[21]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

25.5

Confidence interval

level

95%

sides

2-sided

lower limit

16.8

upper limit

34.2

Notes
[20] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[21] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 8 in IFC compared to ST arm [ITT analysis set].

Day 9: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[22]

P-value

< 0.0001 ^[23]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

10.5

upper limit

27.4

Notes
[22] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[23] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 9 in IFC compared to ST arm [ITT analysis set].

Day 10: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[24]

P-value

= 0.0029 ^[25]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

11.7

Confidence interval

level

95%

sides

2-sided

lower limit

3.7

upper limit

19.7

Notes
[24] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[25] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 10 in IFC compared to ST arm [ITT analysis set].

Day 11: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[26]

P-value

= 0.0072 ^[27]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

17.7

Notes
[26] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).
[27] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with URTI symptom alleviation (“Response”) at study day 11 in IFC compared to ST arm [ITT analysis set].

Day 12: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[28]

P-value

= 0.0809

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

13.1

Notes
[28] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).

Day 13: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[29]

P-value

= 0.0822

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

12.1

Notes
[29] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).

Day 14: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[30]

P-value

= 0.358

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

8.8

Notes
[30] - Contributing categories are "No" and "Yes". Missing data category, resulting from invalid diary data is not taken into account (invalid diary data was observed for 4 patients of ST and 2 patients of IFC arm, respectively).

Secondary: Fraction of patients with maintenance of symptom alleviation as defined for primary objective until end of study

Top of page

End point title

Fraction of patients with maintenance of symptom alleviation as defined for primary objective until end of study

End point description

Subjects who showed URTI symptom alleviation as defined for primary endpoint within study period were evaluated for duration of (initial) response's duration. Only patients with occurrence of symptom alleviation are shown. Patients not showing URTI symptom alleviation throughout the whole study period are not considered.

End point type

Secondary

End point timeframe

study day 2 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	228 ^[31]	242 ^[32]
Units: patients
Maintenance until end of study	199	213
Reoccurrence of symptom(s)	29	29

Notes
[31] - 24 patients had no symptom at all during the whole study.
[32] - 17 patients had no symptom at all during the whole study.

No statistical analyses for this end point

Secondary: Time to return to normal daily activity [investigators' assessment]

Top of page

End point title

Time to return to normal daily activity [investigators' assessment]

End point description

Patients who were rated as having an impaired ability to perform their normal daily activities at baseline visit were evaluated for their individual time to return to normal daily activity, as assessed by the physician at FU calls and visits. The table shows the cumulated number of patients resuming normal daily activity at respective call/visit or earlier (Note: categories are ordered with respect to study schedule).

End point type

Secondary

End point timeframe

1st FU call, 2nd FU call, 1st FU visit, 2nd FU visit and termination visit

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	209 ^[33]	196 ^[34]
Units: patients
1st FU call (day 2)	11	11
2nd FU call (day 3)	30	41
1st FU visit (day 4±1)	58	94
2nd FU visit (day 8±1 )	136	171
Termination visit (day 15 ±2)	196	186

Notes
[33] - 47 ST arm [ITT set] patients had no impairment at baseline and are therefore not considered.
[34] - 65 IFC arm [ITT set] patients had no impairment at baseline and are therefore not considered.

FU call 1:Equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of patients patients resuming normal daily activity at FU call 1. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

other ^[35]

P-value

= 0.8769

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-4.57

upper limit

5.26

Notes
[35] - Binary categorization of "Resumption normal daily activity at FU call 1" [Yes/No] based on cumulated counts is basis for presented statistical test.

FU call 2:Equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of patients patients resuming normal daily activity at or prior to FU call 2. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

other ^[36]

P-value

= 0.0825

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

6.56

Confidence interval

level

95%

sides

2-sided

lower limit

-1.35

upper limit

14.48

Notes
[36] - Binary categorization of "Resumption normal daily activity at or prior to FU call 2" [Yes/No] based on cumulated counts is basis for presented statistical test.

FU visit1:Equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of patients patients resuming normal daily activity at or prior to FU visit 1. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

other ^[37]

P-value

< 0.0001 ^[38]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

20.21

Confidence interval

level

95%

sides

2-sided

lower limit

10.46

upper limit

29.96

Notes
[37] - Binary categorization of "Resumption normal daily activity at or prior to FU visit 1" [Yes/No] based on cumulated counts is basis for presented statistical test.
[38] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with resumption normal daily activity at or prior to FU visit 1 in IFC compared to ST arm [ITT analysis set].

FU visit2:Equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of patients patients resuming normal daily activity at or prior to FU visit 2. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

other ^[39]

P-value

< 0.0001 ^[40]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

22.17

Confidence interval

level

95%

sides

2-sided

lower limit

13.7

upper limit

30.64

Notes
[39] - Binary categorization of "Resumption normal daily activity at or prior to FU visit 2" [Yes/No] based on cumulated counts is basis for presented statistical test.
[40] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with resumption normal daily activity at or prior to FU visit 2 in IFC compared to ST arm [ITT analysis set].

T. visit :Equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of patients patients resuming normal daily activity at or prior to termination visit. (Only patients with impairment of normal daily activities as assessed at baseline are considered in analysis.) Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

other ^[41]

P-value

= 0.6271

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-3.87

upper limit

6.11

Notes
[41] - Binary categorization of "Resumption normal daily activity at or prior to termination visit" [Yes/No] based on cumulated counts is basis for presented statistical test.

Secondary: Resolution of individual symptoms (analysed via WURSS-21)

Top of page

End point title

Resolution of individual symptoms (analysed via WURSS-21)

End point description

WURSS-21 items 2-20 assessed in patients diary are basis for individual symptom resolution evaluation. Between each distinct item, the number of subjects initially suffering a respective symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1') may differ. The table therefore presents (i) the number of patients initially suffering from symptom /item, (ii) the number of patients with symptom resolved within study period - by WURSS-21 item. Note that the number of patients with symptom remaining unresolved at the end of study is the difference between (i) and (ii). The endpoint has been evaluated for N=504 ITT analysis set patients, as for N=6 patients (ST=4; IFC=2) no diary WURSS-21 records were available and for additional N=7 patients (ST=2; IFC=5) no baseline WURSS-21 questionnaire rating was available.

End point type

Secondary

End point timeframe

study day 2 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	250 ^[42]	254 ^[43]
Units: patients
Item 2: Present impairment at baseline	184	173
Item 2: Resolution within study period	169	165
Item 3: Present impairment at baseline	194	199
Item 3: Resolution within study period	177	190
Item 4: Present impairment at baseline	176	165
Item 4: Resolution within study period	168	162
Item 5: Present impairment at baseline	182	186
Item 5: Resolution within study period	171	184
Item 6: Present impairment at baseline	182	194
Item 6: Resolution within study period	172	188
Item 7: Present impairment at baseline	194	184
Item 7: Resolution within study period	173	166
Item 8: Present impairment at baseline	141	150
Item 8: Resolution within study period	132	146
Item 9: Present impairment at baseline	208	204
Item 9: Resolution within study period	199	200
Item10: Present impairment at baseline	103	97
Item 10: Resolution within study period	97	95
Item11: Present impairment at baseline	238	244
Item11: Resolution within study period	220	237
Item12: Present impairment at baseline	183	171
Item12: Resolution within study period	171	163
Item13: Present impairment at baseline	220	229
Item13: Resolution within study period	203	216
Item14: Present impairment at baseline	217	216
Item14: Resolution within study period	200	200
Item15: Present impairment at baseline	211	210
Item15: Resolution within study period	191	202
Item16: Present impairment at baseline	208	215
Item16: Resolution within study period	192	207
Item17: Present impairment at baseline	207	213
Item17: Resolution within study period	191	205
Item18: Present impairment at baseline	208	215
Item18: Resolution within study period	195	207
Item19: Present impairment at baseline	202	211
Item19: Resolution within study period	187	203
Item20: Present impairment at baseline	200	213
Item20: Resolution within study period	187	205

Notes
[42] - 6 ST arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.
[43] - 7 IFC arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.

Item 2: Equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis referring to observed resolution within study period [Yes/No] within those patients initially suffering from symptom (assessed by baseline WURSS-21 questionnaire item ratings '>1'). Presented values for risk difference are related to the difference in patients with resolution of symptom between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[44]

P-value

= 0.1748

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

3.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.08

upper limit

9.13

Notes
[44] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item 3: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[45]

P-value

= 0.0909

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

4.24

Confidence interval

level

95%

sides

2-sided

lower limit

-1.18

upper limit

9.67

Notes
[45] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item 4: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[46]

P-value

= 0.1543

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

2.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.55

upper limit

7.01

Notes
[46] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item 5: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[47]

P-value

= 0.0098 ^[48]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

4.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

9.28

Notes
[47] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
[48] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with item 5 resolution in IFC compared to ST arm [ITT analysis set].

Item 6: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[49]

P-value

= 0.2489

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

7.04

Notes
[49] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item 7: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[50]

P-value

= 0.7392

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

-5.61

upper limit

7.7

Notes
[50] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item 8: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[51]

P-value

= 0.1251

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

3.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.76

upper limit

9.19

Notes
[51] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item 9: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[52]

P-value

= 0.1695

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

2.37

Confidence interval

level

95%

sides

2-sided

lower limit

-1.48

upper limit

6.21

Notes
[52] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item 10: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[53]

P-value

= 0.1747

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

3.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2.57

upper limit

10.1

Notes
[53] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item11: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[54]

P-value

= 0.0202 ^[55]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

4.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

9.07

Notes
[54] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
[55] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with item 11 resolution in IFC compared to ST arm [ITT analysis set].

Item12: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[56]

P-value

= 0.4442

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

1.88

Confidence interval

level

95%

sides

2-sided

lower limit

-3.47

upper limit

7.23

Notes
[56] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item13: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[57]

P-value

= 0.3844

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

2.05

Confidence interval

level

95%

sides

2-sided

lower limit

-3.02

upper limit

7.13

Notes
[57] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item14: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[58]

P-value

= 0.8671

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-5.03

upper limit

5.89

Notes
[58] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item15: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[59]

P-value

= 0.0196 ^[60]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

5.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

10.87

Notes
[59] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.
[60] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher number of patients with item 15 resolution in IFC compared to ST arm [ITT analysis set].

Item16: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[61]

P-value

= 0.0775

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

3.97

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

8.86

Notes
[61] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item17: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[62]

P-value

= 0.0794

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

3.97

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

8.89

Notes
[62] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item18: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[63]

P-value

= 0.2312

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

2.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.09

upper limit

7.15

Notes
[63] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item19: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[64]

P-value

= 0.1074

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

3.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.29

upper limit

8.56

Notes
[64] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Item20: Equality of fractions between arms [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[65]

P-value

= 0.2046

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

2.74

Confidence interval

level

95%

sides

2-sided

lower limit

-2.01

upper limit

7.49

Notes
[65] - The total number of patients contributing to this analysis is the number of patients with "item's impairment present at baseline" for each comparison group.

Secondary: Time to resolution of individual symptoms (analysed via diary WURSS-21)

Top of page

End point title

Time to resolution of individual symptoms (analysed via diary WURSS-21)

End point description

Analysis refers to the observed time point, when an item's resolution within study period was recorded in patients diary. Only patients with corresponding "item's impairment present at baseline" who showed resolution within study period contribute to this analysis. The endpoint has been evaluated for N=504 ITT analysis set patients, as for N=6 patients (ST=4; IFC=2) no diary WURSS-21 records were available and for additional N=7 patients (ST=2; IFC=5) no baseline WURSS-21 questionnaire rating was available. As stated above, the number of analysed patients differs between items, depending on the number of patients with observed resolution. [Please also refer to endpoint 'Resolution of individual symptoms (analysed via WURSS-21)']

End point type

Secondary

End point timeframe

study day 2 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	250 ^[66]	254 ^[67]
Units: [days]
median (inter-quartile range (Q1-Q3))
Item 2 (Runny nose)	8 (6 to 10)	6 (4 to 8)
Item 3 (Plugged nose)	8 (5 to 9)	6 (4 to 8)
Item 4 (Sneezing)	6 (4 to 8)	4 (3 to 6)
Item 5 (Sore throat)	6 (5 to 8)	5 (4 to 7)
Item 6 (Scratchy throat)	6 (4 to 8)	5 (4 to 7)
Item 7 (Cough)	9 (7 to 11)	7 (4 to 9)
Item 8 (Hoarseness)	6 (3 to 8)	4 (3 to 7)
Item 9 (Head congestion)	6 (5 to 8)	4 (3 to 6)
Item 10 (Chest congestion)	7 (4 to 10)	5 (3 to 8)
Item 11 (Feeling tired)	8 (6 to 10)	6 (4 to 7)
Item 12 (Think clearly)	7 (5 to 9)	5 (4 to 7)
Item 13 (Sleep well)	7 (5 to 9)	5 (3 to 7)
Item 14 (Breathe easily)	8 (5 to 9)	6 (4 to 7)
Item 15 (Walk / climb stairs / exercise)	8 (6 to 10)	6 (4 to 7)
Item 16 (Accomplish daily activities)	8 (6 to 9)	6 (4 to 7)
Item 17 (Work outside the home)	8 (6 to 10)	6 (4 to 7)
Item 18 (Work inside the home)	7 (5 to 9)	5 (4 to 7)
Item 19 (Interact with others)	7 (5 to 9)	5 (4 to 7)
Item 20 (Live your personal life)	7 (5 to 9)	5 (4 to 7)

Notes
[66] - 6 ST arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.
[67] - 7 IFC arm [ITT set] patients had either missing baseline WURSS-21 questionnaire or no diary data.

Item 2: Time to symptom resolution [ITT]

Statistical analysis description

Explorative analysis of individual item’s/ symptom’s time to resolution. Time to symptom resolution [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in time to symptom resolution between treatments taking into account the direction 'IFC - ST'. Negative values indicate a shorter duration until symptom alleviation for IFC patients compared to ST patients.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[68]

P-value

< 0.0001 ^[69]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[68] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[69] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 2.

Item 3: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[70]

P-value

< 0.0001 ^[71]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[70] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[71] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 3.

Item 4: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[72]

P-value

< 0.0001 ^[73]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[72] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[73] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 4.

Item 5: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[74]

P-value

< 0.0001 ^[75]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[74] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[75] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 5.

Item 6: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[76]

P-value

= 0.0003 ^[77]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

Notes
[76] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[77] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 6.

Item 7: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[78]

P-value

< 0.0001 ^[79]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Notes
[78] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[79] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 7.

Item 8: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[80]

P-value

= 0.0015 ^[81]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

Notes
[80] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[81] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 8.

Item 9: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[82]

P-value

< 0.0001 ^[83]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[82] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[83] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 9.

Item10: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[84]

P-value

= 0.0012 ^[85]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Notes
[84] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[85] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 10.

Item11: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[86]

P-value

< 0.0001 ^[87]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[86] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[87] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 11.

Item12: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[88]

P-value

< 0.0001 ^[89]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[88] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[89] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 12.

Item13: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[90]

P-value

< 0.0001 ^[91]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[90] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[91] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 13.

Item14: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[92]

P-value

< 0.0001 ^[93]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[92] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[93] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 14.

Item15: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[94]

P-value

< 0.0001 ^[95]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[94] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[95] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 15.

Item16: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[96]

P-value

< 0.0001 ^[97]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[96] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[97] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 16.

Item17: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[98]

P-value

< 0.0001 ^[99]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[98] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[99] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 17.

Item18: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[100]

P-value

< 0.0001 ^[101]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[100] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[101] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 18.

Item19: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[102]

P-value

< 0.0001 ^[103]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[102] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[103] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 19.

Item20: Time to symptom resolution [ITT]

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[104]

P-value

< 0.0001 ^[105]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[104] - The total number of patients contributing to this test is the number of patients with item's “Resolution within study period” as presented in secondary end point “Resolution of individual symptoms (analysed via WURSS-21)”.
[105] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter time to symptom resolution [days] in IFC compared to ST arm [ITT analysis set] for WURSS-21 item 20.

Secondary: Area under the curve (AUC) describing severity and course of the infection

Top of page

End point title

Area under the curve (AUC) describing severity and course of the infection

End point description

WURSS-21 questionnaire was answered by patients/parents twice a day. The cumulated (until study day 14) scorings for symptom (items2-11), quality of life (items12-20) and total (items 2-20) sum scores are shown here. In order to be able to compare between time-related randomization groups (i.e. patients randomized "till noon" or "after noon"), analysis was based on distance to baseline [DTB] (Evaluation “per day” would skew the calculation results as “till noon patients” would have answered one additional questionnaire compared to “after noon patients”). Presented AUC values refer to DTB=13.5. The endpoint has been evaluated for N=504 ITT analysis set patients, as for N=6 patients (ST=4; IFC=2) no diary WURSS-21 records were available and for additional N=7 patients (ST=2; IFC=5) no baseline WURSS-21 questionnaire rating was available. Please note that due to missing single items in baseline WURSS-21 questionnaire, AUC for sum scores could not be derived for all 504 analyzed patients.

End point type

Secondary

End point timeframe

study day 2 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	250 ^[106]	254 ^[107]
Units: SCORE
median (inter-quartile range (Q1-Q3))
Symptom sum score (WURSS items 2-11)	425 (289.5 to 610.5)	304 (197 to 453)
QoL sum score (WURSS items 12-20)	484 (285 to 710)	342 (192 to 524)
Total sum score (WURSS items 2-20)	928 (597 to 1312)	643.5 (395 to 952)

Notes
[106] - Thereof subjects with evaluable data per sum score: Symptom: N=240 | QoL: N= 234 | Total: N= 230
[107] - Thereof subjects with evaluable data per sum score: Symptom: N=242 | QoL: N= 247 | Total: N= 238

AUC: Symptom sum score [ITT]

Statistical analysis description

Explorative analysis of symptom sum score as calculated from WURSS-21 questionnaire items 2 to 11. Sum score AUC values were tested for treatment related differences. Presented values for estimated location shift are related to the difference in AUC between treatments taking into account the direction 'IFC - ST'. Negative values indicate lower scores (lower severity) for IFC group patients compared to ST group patients.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[108]

P-value

< 0.0001 ^[109]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-111

Confidence interval

level

95%

sides

2-sided

lower limit

-149

upper limit

-74

Notes
[108] - The total number of patients contributing to this test is the number of patients with valid baseline assessment for contributing to score calculation WURSS-21 items (2-11).
[109] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower severity (WURSS-21 symptom sum score) within study period in IFC compared to ST arm [ITT analysis set].

AUC: QoL sum score [ITT]

Statistical analysis description

Explorative analysis of QoL sum score as calculated from WURSS-21 questionnaire items 12 to 20. Sum score AUC values were tested for treatment related differences. Presented values for estimated location shift are related to the difference in AUC between treatments taking into account the direction 'IFC - ST'. Negative values indicate lower scores (lower severity) for IFC group patients compared to ST group patients.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[110]

P-value

< 0.0001 ^[111]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-127

Confidence interval

level

95%

sides

2-sided

lower limit

-175

upper limit

-76

Notes
[110] - The total number of patients contributing to this test is the number of patients with valid baseline assessment for contributing to score calculation WURSS-21 items (12-20).
[111] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower severity (WURSS-21 QoL sum score) within study period in IFC compared to ST arm [ITT analysis set].

AUC: Total sum score [ITT]

Statistical analysis description

Explorative analysis of total sum score as calculated from WURSS-21 questionnaire items 2 to 20. Sum score AUC values were tested for treatment related differences. Presented values for estimated location shift are related to the difference in AUC between treatments taking into account the direction 'IFC - ST'. Negative values indicate lower scores (lower severity) for IFC group patients compared to ST group patients.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

504

Analysis specification

Pre-specified

Analysis type

other ^[112]

P-value

< 0.0001 ^[113]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-246

Confidence interval

level

95%

sides

2-sided

lower limit

-331

upper limit

-162

Notes
[112] - The total number of patients contributing to this test is the number of patients with valid baseline assessment for contributing to score calculation WURSS-21 items (2-20).
[113] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower severity (WURSS-21 total sum score) within study period in IFC compared to ST arm [ITT analysis set].

Secondary: Total amount and amount per day of paracetamol consumption

Top of page

End point title

Total amount and amount per day of paracetamol consumption

End point description

Paracetamol has been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The total amount [mg] of medication taken as well as the amount [mg] per day (average dosage) were calculated by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom paracetamol has been actually dispensed. [Note: Presented values refer to the amount of active substance.]

End point type

Secondary

End point timeframe

study day 1 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	252 ^[114]	259 ^[115]
Units: mg
median (inter-quartile range (Q1-Q3))
Total amount [mg] (all patients)	1750 (400 to 5450)	600 (0 to 2200)
Total amount [mg] (dispensed medication)	2200 (800 to 6000)	1000 (400 to 2600)
Average dosage [mg] (all patients)	533.3 (200 to 1020.5)	300 (0 to 750)
Average dosage [mg] (dispensed medication)	600 (400 to 1100)	466.7 (200 to 800)

Notes
[114] - 4 ST [ITT] patients had no valid diary data. Paracetamol dispense was recorded for N=228 patients.
[115] - 2 IFC [ITT] patients had no valid diary data. Paracetamol dispense was recorded for N=205 patients.

Paracetamol: Total amount (all patients) [ITT]

Statistical analysis description

Explorative analysis of the total (cumulated) amount of paracetamol taken. Analysis accounts for all patients with valid diary data. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed paracetamol between treatments taking into account the direction 'IFC - ST'

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[116]

P-value

< 0.0001 ^[117]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-900

Confidence interval

level

95%

sides

2-sided

lower limit

-1400

upper limit

-500

Notes
[116] - Analysis is based on diary data entries from all patients with valid diary data.
[117] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].

Paracetamol: Total amount (dispensed medication)

Statistical analysis description

Explorative analysis of the total (cumulated) amount of paracetamol taken. Analysis accounts for all patients with valid diary data to whom paracetamol has been dispensed. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed paracetamol between treatments taking into account the direction 'IFC - ST'

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[118]

P-value

< 0.0001 ^[119]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1000

Confidence interval

level

95%

sides

2-sided

lower limit

-1500

upper limit

-600

Notes
[118] - Analysis is based on valid diary data entries from patients with recorded dispense of paracetamol (as prescribed by treating physician on his/her discretion).
[119] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].

Paracetamol: Average dosage (all patients) [ITT]

Statistical analysis description

Explorative analysis of the average amount of paracetamol taken by all patients with valid diary data is defined as the cumulated amount of paracetamol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in paracetamol dosis between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[120]

P-value

< 0.0001 ^[121]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-200

Confidence interval

level

95%

sides

2-sided

lower limit

-300

upper limit

-100

Notes
[120] - Analysis is based on diary data entries from all patients with valid diary data.
[121] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].

Paracetamol: Average dosage (dispensed medication)

Statistical analysis description

Explorative analysis of the average amount of paracetamol taken by all patients with valid diary data to whom paracetamol has been dispensed, which is defined as the cumulated amount of paracetamol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in paracetamol dosis between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[122]

P-value

= 0.0005 ^[123]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-175

Confidence interval

level

95%

sides

2-sided

lower limit

-250

upper limit

-65

Notes
[122] - Analysis is based on valid diary data entries from patients with recorded dispense of paracetamol.
[123] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of paracetamol consumed in IFC compared to ST arm [ITT analysis set].

Secondary: Total amount and amount per day of ambroxol consumption

Top of page

End point title

Total amount and amount per day of ambroxol consumption

End point description

Ambroxol has been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The total amount [mg] of medication taken as well as the amount [mg] per day were calculated by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom ambroxol has been actually dispensed. [Note: Presented values refer to the amount of active substance.]

End point type

Secondary

End point timeframe

study day 1 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	252 ^[124]	259 ^[125]
Units: [mg]
median (inter-quartile range (Q1-Q3))
Total amount [mg] (all patients)	315 (112.5 to 630)	112.5 (0 to 390)
Total amount [mg] (dispensed medication)	375 (157.5 to 660)	240 (75 to 501)
Average dosage [mg] (all patients)	38 (17.7 to 69.5)	22 (0 to 55.7)
Average dosage [mg] (dispensed medication)	42.5 (22.5 to 72.9)	37.5 (20 to 70)

Notes
[124] - 4 ST [ITT] patients had no valid diary data. Ambroxol dispense was recorded for N=227 patients.
[125] - 2 IFC [ITT] patients had no valid diary data. Ambroxol dispense was recorded for N=187 patients.

Ambroxol: Total amount (all patients) [ITT]

Statistical analysis description

Explorative analysis of the total (cumulated) amount of ambroxol taken. Analysis accounts for all patients with valid diary data. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed ambroxol between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[126]

P-value

< 0.0001 ^[127]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-135

Confidence interval

level

95%

sides

2-sided

lower limit

-180

upper limit

-90

Notes
[126] - Analysis is based on diary data entries from all patients with valid diary data.
[127] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of ambroxol consumed in IFC compared to ST arm [ITT analysis set].

Ambroxol: Total amount (dispensed medication)

Statistical analysis description

Explorative analysis of the total (cumulated) amount of ambroxol taken. Analysis accounts for all patients with valid diary data to whom ambroxol has been dispensed. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed ambroxol between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[128]

P-value

= 0.0004 ^[129]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-97.5

Confidence interval

level

95%

sides

2-sided

lower limit

-150

upper limit

-45

Notes
[128] - Analysis is based on valid diary data entries from patients with recorded dispense of ambroxol.
[129] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of ambroxol consumed in IFC compared to ST arm [ITT analysis set].

Ambroxol: Average dosage (all patients) [ITT]

Statistical analysis description

Explorative analysis of the average amount of ambroxol taken by all patients with valid diary data is defined as the cumulated amount of ambroxol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in ambroxol dosis between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[130]

P-value

< 0.0001 ^[131]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-11.25

Confidence interval

level

95%

sides

2-sided

lower limit

-17.8

upper limit

-4

Notes
[130] - Analysis is based on diary data entries from all patients with valid diary data.
[131] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of ambroxol consumed in IFC compared to ST arm [ITT analysis set].

Ambroxol: Average dosage (dispensed medication)

Statistical analysis description

Explorative analysis of the average amount of ambroxol taken by all patients with valid diary data to whom ambroxol has been dispensed, which is defined as the cumulated amount of ambroxol taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in ambroxol dosis between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[132]

P-value

= 0.1971

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

1.3

Notes
[132] - Analysis is based on valid diary data entries from patients with recorded dispense of ambroxol.

Secondary: Total amount and amount per day of oxymetazoline consumption

Top of page

End point title

Total amount and amount per day of oxymetazoline consumption

End point description

Oxymetazoline has been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The total amount [μg] of medication taken as well as the amount [μg] per day were calculated by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom oxymetazoline has been actually dispensed. [Note: Presented values refer to the amount of active substance.]

End point type

Secondary

End point timeframe

study day 1 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	252 ^[133]	259 ^[134]
Units: [µg]
median (inter-quartile range (Q1-Q3))
Total amount [µg] (all patients)	720 (253.1 to 1080)	292.5 (0 to 675)
Total amount [µg] (dispensed medication)	810 (472.5 to 1147.5)	472.5 (202.5 to 810)
Average dosage [µg] (all patients)	96.3 (48.9 to 135)	60.8 (0 to 112.5)
Average dosage [µg] (dispensed medication)	108.4 (61.9 to 135)	80.3 (45 to 127)

Notes
[133] - 4 ST [ITT] patients had no valid diary data. Oxymetazoline dispense was listed for N=222 patients.
[134] - 2 IFC [ITT] patients had no valid diary data. Oxymetazoline dispense was listed for N=196 patients.

Oxymetazoline: Total amount (all patients) [ITT]

Statistical analysis description

Explorative analysis of the total (cumulated) amount of oxymetazoline taken. Analysis accounts for all patients with valid diary data. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed oxymetazoline between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[135]

P-value

< 0.0001 ^[136]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-315

Confidence interval

level

95%

sides

2-sided

lower limit

-405

upper limit

-202.5

Notes
[135] - Analysis is based on diary data entries from all patients with valid diary data.
[136] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

Oxymetazoline: Total amount (dispensed medication)

Statistical analysis description

Explorative analysis of the total (cumulated) amount of oxymetazoline taken. Analysis accounts for all patients with valid diary data to whom oxymetazoline has been dispensed. The total amount was tested for treatment related differences. Presented values for estimated location shift are related to the difference in consumed oxymetazoline between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[137]

P-value

< 0.0001 ^[138]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-270

Confidence interval

level

95%

sides

2-sided

lower limit

-360

upper limit

-157.5

Notes
[137] - Analysis is based on valid diary data entries from patients with recorded dispense of oxymetazoline.
[138] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

Oxymetazoline: Average dosage (all patients) [ITT]

Statistical analysis description

Explorative analysis of the average amount of oxymetazoline taken by all patients with valid diary data is defined as the cumulated amount of oxymetazoline taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in oxymetazoline dosis between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[139]

P-value

< 0.0001 ^[140]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-28.1

Confidence interval

level

95%

sides

2-sided

lower limit

-43.4

upper limit

-13.5

Notes
[139] - Analysis is based on diary data entries from all patients with valid diary data.
[140] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

Oxymetazoline:Average dosage(dispensed medication)

Statistical analysis description

Explorative analysis of the average amount of oxymetazoline taken by all patients with valid diary data to whom oxymetazoline has been dispensed, which is defined as the cumulated amount of oxymetazoline taken by these patients divided by the number of days of intake. The average dosage was tested for treatment related differences. Presented values for estimated location shift are related to the difference in oxymetazoline dosis between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[141]

P-value

= 0.0026 ^[142]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-16.9

Confidence interval

level

95%

sides

2-sided

lower limit

-29.25

upper limit

-4.5

Notes
[141] - Analysis is based on valid diary data entries from patients with recorded dispense of oxymetazoline.
[142] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower average amount of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

Secondary: Duration of symptomatic medication consumption

Top of page

End point title

Duration of symptomatic medication consumption

End point description

Symptomatic medication (paracetamol, ambroxol, oxymetazoline 0.05% and 0.025%) have been dispensed at discretion of the treating physician. Intake has been recorded in patient diary. The number of days with recorded symptomatic medication intake is presented by considering (i) all patients with valid diary data [N=511; ITT both arms] and (ii) only those patients with valid diary data, to whom symptomatic medication has been actually dispensed. Number of days with individual substances (paracetamol, ambroxol and oxymetazoline) as well as with "any symptomatic medication" is presented. [Note: The number of patients with distinct symptomatic medication actually dispensed may be obtained from respective 'Total amount and amount per day' endpoint data presentations.]

End point type

Secondary

End point timeframe

study day 1 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	252 ^[143]	259 ^[144]
Units: [days]
median (inter-quartile range (Q1-Q3))
Days with: Any sympt.med. (all patients)	9 (7 to 12)	6 (4 to 9)
Days with: Any sympt.med. (dispensed medication)	9 (7 to 12)	7 (5 to 9)
Days with: paracetamol (all patients)	3 (1 to 5)	2 (0 to 3)
Days with: paracetamol (dispensed medication)	4 (2 to 5)	2 (1 to 3)
Days with: ambroxol (all patients)	8 (5 to 11)	4 (0 to 8)
Days with: ambroxol (dispensed medication)	8 (6 to 12)	6 (4 to 9)
Days with: oxymetazoline (all patients)	7 (4 to 9)	4 (0 to 7)
Days with: oxymetazoline (dispensed medication)	7 (6 to 10)	5 (3 to 8)

Notes
[143] - 4 ST [ITT] patients had no valid diary. Any sympt. med. dispense was recorded for N=252 patients.
[144] - 2 IFC [ITT] patients had no valid diary. Any sympt. med. dispense was lrecorded for N=234 patients.

Duration: Any sympt.med. (all patients) [ITT]

Statistical analysis description

Explorative analysis of any symptomatic medication intake duration for all patients with valid diary data is defined as the number of days with any symptomatic medication intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of any symptomatic medication intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[145]

P-value

< 0.0001 ^[146]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-2

Notes
[145] - Analysis is based on diary data entries from all patients with valid diary data.
[146] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of any symptomatic medication consumed in IFC compared to ST arm [ITT analysis set].

Duration: Any sympt.med. (dispensed medication)

Statistical analysis description

Explorative analysis of any symptomatic medication intake duration for all patients with valid diary data to whom any symptomatic medication was dispensed is defined as the number of days of any symptomatic medication intake as recorded in patient diary for those patients. Duration was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[147]

P-value

< 0.0001 ^[148]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Notes
[147] - Analysis is based on valid diary data entries from patients with recorded dispense of either paracetamol, ambroxol or oxymetazoline.
[148] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of any symptomatic medication consumed in IFC compared to ST arm [ITT analysis set].

Duration: Paracetamol (all patients) [ITT]

Statistical analysis description

Explorative analysis of paracetamol intake duration for all patients with valid diary data is defined as the number of days with paracetamol intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of paracetamol intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[149]

P-value

< 0.0001 ^[150]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[149] - Analysis is based on diary data entries from all patients with valid diary data.
[150] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of paracetamol consumed in IFC compared to ST arm [ITT analysis set].

Duration: Ambroxol (all patients) [ITT]

Statistical analysis description

Explorative analysis of ambroxol intake duration for all patients with valid diary data is defined as the number of days with ambroxol intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of ambroxol intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[151]

P-value

< 0.0001 ^[152]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-2

Notes
[151] - Analysis is based on diary data entries from all patients with valid diary data.
[152] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of ambroxol consumed in IFC compared to ST arm [ITT analysis set].

Duration: Paracetamol (dispensed medication) [ITT]

Statistical analysis description

Explorative analysis of paracetamol intake duration for all patients with valid diary data to whom paracetamol was dispensed is defined as the number of days of paracetamol intake as recorded in patient diary for those patients. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of paracetamol intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[153]

P-value

< 0.0001 ^[154]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[153] - Analysis is based on valid diary data entries from patients with recorded dispense of paracetamol.
[154] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of paracetamol consumed in IFC compared to ST arm [ITT analysis set].

Duration: Ambroxol (dispensed medication) [ITT]

Statistical analysis description

Explorative analysis of ambroxol intake duration for all patients with valid diary data to whom ambroxol was dispensed is defined as the number of days of ambroxol intake as recorded in patient diary for those patients. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of ambroxol intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[155]

P-value

< 0.0001 ^[156]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Notes
[155] - Analysis is based on valid diary data entries from patients with recorded dispense of ambroxol.
[156] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of ambroxol consumed in IFC compared to ST arm [ITT analysis set].

Duration: Oxymetazoline (all patients) [ITT]

Statistical analysis description

Explorative analysis of oxymetazoline intake duration for all patients with valid diary data is defined as the number of days with oxymetazoline intake as recorded in patient diary. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of oxymetazoline intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[157]

P-value

< 0.0001 ^[158]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Notes
[157] - Analysis is based on diary data entries from all patients with valid diary data.
[158] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

Duration: Oxymetazoline(dispensed medication)[ITT]

Statistical analysis description

Explorative analysis of oxymetazoline intake duration for all patients with valid diary data to whom oxymetazoline was dispensed is defined as the number of days of oxymetazoline intake as recorded in patient diary for those patients. The duration [days] was tested for treatment related differences. Presented values for estimated location shift are related to the difference in duration of oxymetazoline intake between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

511

Analysis specification

Pre-specified

Analysis type

other ^[159]

P-value

< 0.0001 ^[160]

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges Lehman estimate of location shift

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Notes
[159] - Analysis is based on valid diary data entries from patients with recorded dispense of oxymetazoline.
[160] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly shorter duration of oxymetazoline consumed in IFC compared to ST arm [ITT analysis set].

Secondary: Fraction of patients who must be withdrawn from the study due to prohibited medication

Top of page

End point title

Fraction of patients who must be withdrawn from the study due to prohibited medication

End point description

The analysis of withdrawals due to prohibited medication was based on the consumption of concomitant medication recorded in the diary and CRF.

End point type

Secondary

End point timeframe

study day 2 to study day 14

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	256	261
Units: patients
Withdrawal due to prohibited medication	9	5
No withdrawal OR not due to prohibited medication	247	256

Test for equality of fractions between arms [ITT]

Statistical analysis description

Explorative analysis of fraction of patients who must be withdrawn from the study due to prohibited medication. Presented values for risk difference are related to the difference in prohibited medication related withdrawals between treatments taking into account the direction 'IFC - ST'

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2625

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

1.6

Secondary: Treatment outcome according to integrative medicine outcomes scale (IMOS)

Top of page

End point title

Treatment outcome according to integrative medicine outcomes scale (IMOS)

End point description

Treatment outcome was assessed by both the investigator and the patient at each study visit using IMOS (5-point rating scale). Distinct values are presented for physicians and patients answers. The total number of patients assessments varies between presented visits as discontinuations occured between visits.

End point type

Secondary

End point timeframe

1st FU visit, 2nd FU visit and termination visit

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	256 ^[161]	261 ^[162]
Units: patients
1st FU V.: Complete recovery (physician)	5	13
1st FU V.: Major improvement (physician)	62	143
1st FU V.: Slight to moderate improvement (phys.)	121	82
1st FU V.: No change (physician)	54	17
1st FU V.: Deterioration (physician)	14	6
2nd FU V.: Complete recovery (physician)	28	118
2nd FU V.: Major improvement (physician)	164	121
2nd FU V.: Slight to moderate improvement (phys.)	48	16
2nd FU V.: No change (physician)	5	0
2nd FU V.: Deterioration (physician)	6	4
Term. V.: Complete recovery (physician)	186	225
Term. V.: Major improvement (physician)	47	22
Term. V.: Slight to moderate improvement (phys.)	10	2
Term. V.: No change (physician)	0	3
Term. V.: Deterioration (physician)	3	4
1st FU V.: Complete recovery (patient)	7	18
1st FU V.: Major improvement (patient)	58	129
1st FU V.: Slight to moderate improvement (pat.)	121	89
1st FU V.: No change (patient)	52	17
1st FU V.: Deterioration (patient)	18	8
2nd FU V.: Complete recovery (patient)	29	115
2nd FU V.: Major improvement (patient)	164	126
2nd FU V.: Slight to moderate improvement (pat.)	47	14
2nd FU V.: No change (patient)	5	0
2nd FU V.: Deterioration (patient)	6	4
Term. V.: Complete recovery (patient)	191	225
Term. V.: Major improvement (patient)	42	22
Term. V.: Slight to moderate improvement (pat.)	9	2
Term. V.: No change (patient)	1	3
Term. V.: Deterioration (patient)	3	4

Notes
[161] - Total assessments per visit: 1st FU: N=256 2ndFU: N=252 Termination: N=246
[162] - Total assessments per visit: 1st FU: N=261 2ndFU: N=259 Termination: N=256

IMOS 1st FU: At least 'major impr.' (patient)[ITT]

Statistical analysis description

Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery or major improvement" and "slight to moderate improvement or no change or deterioration" resulting from combination of IMOS assessment categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[163]

P-value

< 0.001 ^[164]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

30.93

Confidence interval

level

95%

sides

2-sided

lower limit

22.5

upper limit

39.36

Notes
[163] - Analysis refers to patients' assessments.
[164] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].

IMOS 1st FU: At least 'major impr.' (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[165]

P-value

< 0.001 ^[166]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

33.6

Confidence interval

level

95%

sides

2-sided

lower limit

25.19

upper limit

42.01

Notes
[165] - Analysis refers to physicians' assessments.
[166] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].

IMOS 2nd FU: At least 'major impr.' (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[167]

P-value

< 0.001 ^[168]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

16.46

Confidence interval

level

95%

sides

2-sided

lower limit

9.99

upper limit

22.93

Notes
[167] - Analysis refers to patients' assessments. [Note: 1 missing assessment in ST arm.]
[168] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].

IMOS 2nd FU: At least 'major impr.' (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[169]

P-value

< 0.001 ^[170]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

16.09

Confidence interval

level

95%

sides

2-sided

lower limit

9.51

upper limit

22.66

Notes
[169] - Analysis refers to physicians' assessments. [Note: 1 missing assessment in ST arm.]
[170] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with IMOS assessed as 'complete recovery or major improvement’ in IFC compared to ST arm [ITT analysis set].

IMOS Term. V.: At least 'major impr.' (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[171]

P-value

= 0.333

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

-2.22

upper limit

5.76

Notes
[171] - Analysis refers to patients' assessments.

IMOS Term. V.: At least 'major impr.' (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[172]

P-value

= 0.333

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

-2.22

upper limit

5.76

Notes
[172] - Analysis refers to physicians' assessments.

IMOS 1st FU: 'Complete recovery' (patient)

Statistical analysis description

Explorative analysis of combined IMOS categories. Binary categorization of IMOS is done by considering groups "complete recovery" and "major improvement or slight to moderate improvement or no change or deterioration" as resulting from combination of IMOS assessment categories. I.e. binary categorization in terms of complete recovery [Yes/No] is evaluated. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[173]

P-value

= 0.027 ^[174]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

4.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.11

upper limit

8.22

Notes
[173] - Analysis refers to patients' assessments.
[174] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].

IMOS 1st FU: 'Complete recovery' (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[175]

P-value

= 0.06

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

3.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

6.55

Notes
[175] - Analysis refers to physicians' assessments.

IMOS 2nd FU: 'Complete recovery' (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[176]

P-value

< 0.001 ^[177]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

32.89

Confidence interval

level

95%

sides

2-sided

lower limit

25.28

upper limit

40.51

Notes
[176] - Analysis refers to patients' assessments. [Note: 1 missing assessment in ST arm.]
[177] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].

IMOS 2nd FU: 'Complete recovery' (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[178]

P-value

< 0.001 ^[179]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

34.45

Confidence interval

level

95%

sides

2-sided

lower limit

26.86

upper limit

42.04

Notes
[178] - Analysis refers to physicians' assessments. [Note: 1 missing assessment in ST arm.]
[179] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].

IMOS Term. V.: 'Complete recovery' (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[180]

P-value

= 0.002 ^[181]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

10.25

Confidence interval

level

95%

sides

2-sided

lower limit

3.29

upper limit

17.21

Notes
[180] - Analysis refers to patients' assessments.
[181] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].

IMOS Term. V.: 'Complete recovery' (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[182]

P-value

< 0.001 ^[183]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

12.28

Confidence interval

level

95%

sides

2-sided

lower limit

5.19

upper limit

19.37

Notes
[182] - Analysis refers to physicians' assessments.
[183] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of completely recovered patients (IMOS assessment) in IFC compared to ST arm [ITT analysis set].

Secondary: Satisfaction with treatment according to integrative medicine patient satisfaction scale [IMPSS]

Top of page

End point title

Satisfaction with treatment according to integrative medicine patient satisfaction scale [IMPSS]

End point description

IMPSS has been assessed by patients / parents at study termination visit.

End point type

Secondary

End point timeframe

Study termination visit.

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	246 ^[184]	256 ^[185]
Units: patients
not applicable	1	0
Very satisfied	84	196
Satisfied	120	53
Neutral	37	4
Dissatisfied	4	3
Very dissatisfied	0	0

Notes
[184] - Total assessments: Termination: N=246
[185] - Total assessments: Termination: N=256

IMPSS: Very satisfied patients [ITT]

Statistical analysis description

Explorative analysis of combined IMPSS categories. Binary categorization of IMPSS is done by considering the "very satisfied" group against all other categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

502

Analysis specification

Pre-specified

Analysis type

other ^[186]

P-value

< 0.0001 ^[187]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

42.82

Confidence interval

level

95%

sides

2-sided

lower limit

34.56

upper limit

51.08

Notes
[186] - Analysis refers to patients' assessments at termination visit.
[187] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients beeing "very satisfied" (IMPSS) in IFC compared to ST arm [ITT analysis set].

IMPSS: Neutral and dissatisfied patients [ITT]

Statistical analysis description

Explorative analysis of combined IMPSS categories. Binary categorization of IMPSS is done by considering the combined "neutral or dissatisfied or very dissatisfied" group against combination of remaining categories. Presented values for risk difference are related to the difference between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

502

Analysis specification

Pre-specified

Analysis type

other ^[188]

P-value

< 0.0001 ^[189]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-14.75

Confidence interval

level

95%

sides

2-sided

lower limit

-20.29

upper limit

-9.2

Notes
[188] - Analysis refers to patients' assessments at termination visit.
[189] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients beeing "neutral or dissatisfied or very dissatisfied" (IMPSS) in IFC compared to ST arm [ITT analysis set].

Secondary: Patients’ / parents’ assessment of tolerability of treatment

Top of page

End point title

Patients’ / parents’ assessment of tolerability of treatment

End point description

Tolerability of treatment has been assessed by patients / parents and investigators at each of FU calls and visits on a verbal rating scale. Distinct values are presented for physicians and patients answers. The total number of patients assessments varies between presented calls and visits as (i) some calls were not done and (ii) discontinuations have occurred between visits.

End point type

Secondary

End point timeframe

FU calls and visits

End point values	ST arm [ITT analysis set]	IFC arm [ITT analysis set]
Number of subjects analysed	256 ^[190]	261 ^[191]
Units: patients
1st FU call: Excellent (patient)	43	79
1st FU call: Good (patient)	202	179
1st FU call: Moderate (patient)	7	3
1st FU call: Poor (patient)	3	0
1st FU call: not assessed (patient)	1	0
2nd FU call: Excellent (patient)	38	83
2nd FU call: Good (patient)	184	161
2nd FU call: Moderate (patient)	13	3
2nd FU call: Poor (patient)	2	0
2nd FU call: not assessed (patient)	1	0
1st FU visit: Excellent (patient)	55	118
1st FU visit: Good (patient)	183	140
1st FU visit: Moderate (patient)	11	3
1st FU visit: Poor (patient)	4	0
1st FU visit: not assessed (patient)	3	0
2nd FU visit: Excellent (patient)	63	145
2nd FU visit: Good (patient)	174	112
2nd FU visit: Moderate (patient)	9	2
2nd FU visit: Poor (patient)	2	0
2nd FU visit: not assessed (patient)	4	0
Term. visit: Excellent (patient)	70	175
Term. visit: Good (patient)	163	79
Term. visit: Moderate (patient)	7	2
Term. visit: Poor (patient)	2	0
Term. visit: not assessed (patient)	4	0
1st FU call: Excellent (physician)	45	80
1st FU call: Good (physician)	203	178
1st FU call: Moderate (physician)	5	3
1st FU call: Poor (physician)	2	0
1st FU call: not assessed (physician)	1	0
2nd FU call: Excellent (physician)	39	81
2nd FU call: Good (physician)	187	164
2nd FU call: Moderate (physician)	9	2
2nd FU call: Poor (physician)	2	0
2nd FU call: not assessed (physician)	1	0
1st FU visit: Excellent (physician)	55	118
1st FU visit: Good (physician)	185	141
1st FU visit: Moderate (physician)	11	2
1st FU visit: Poor (physician)	2	0
1st FU visit: not assessed (physician)	3	0
2nd FU visit: Excellent (physician)	63	139
2nd FU visit: Good (physician)	175	118
2nd FU visit: Moderate (physician)	9	2
2nd FU visit: Poor (physician)	1	0
2nd FU visit: not assessed (physician)	4	0
Term. visit: Excellent (physician)	71	172
Term. visit: Good (physician)	165	82
Term. visit: Moderate (physician)	5	2
Term. visit: Poor (physician)	1	0
Term. visit: not assessed (physician)	4	0

Notes
[190] - Totals: 1st call: N=256 2nd call: N=238 1st FU V.: N=256 2nd FU V.: N=252 Term. V.: N=246
[191] - Totals: 1st call: N=261 2nd call: N=247 1st FU V.: N=261 2nd FU V.: N=259 Term. V.: N=256

1st FU call: 'Excellent' tolerability (patient)

Statistical analysis description

Explorative analysis of combined tolerability assessment related categories. Binary categorization of tolerability is done by considering the "excellent" category against all other categories. [Note: Missing assessments are not considered.]

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[192]

P-value

= 0.0003 ^[193]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

13.4

Confidence interval

level

95%

sides

2-sided

lower limit

5.8

upper limit

Notes
[192] - Analysis refers to patients' assessments.
[193] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

1st FU call: 'Excellent' tolerability (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[194]

P-value

= 0.0006 ^[195]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.3

upper limit

20.7

Notes
[194] - Analysis refers to physicians' assessments.
[195] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

2nd FU call: 'Excellent' tolerability (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[196]

P-value

< 0.0001 ^[197]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

17.6

Confidence interval

level

95%

sides

2-sided

lower limit

9.6

upper limit

25.5

Notes
[196] - Analysis refers to patients' assessments.
[197] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

2nd FU call: 'Excellent' tolerability (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[198]

P-value

< 0.0001 ^[199]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

16.3

Confidence interval

level

95%

sides

2-sided

lower limit

8.4

upper limit

24.3

Notes
[198] - Analysis refers to physicians' assessments.
[199] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

1st FU visit: 'Excellent' tolerability (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[200]

P-value

< 0.0001 ^[201]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

23.5

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

31.8

Notes
[200] - Analysis refers to patients' assessments.
[201] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

1st FU visit: 'Excellent' tolerability (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[202]

P-value

< 0.0001 ^[203]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

23.5

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

31.8

Notes
[202] - Analysis refers to physicians' assessments.
[203] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

2nd FU visit: 'Excellent' tolerability (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[204]

P-value

< 0.0001 ^[205]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

30.6

Confidence interval

level

95%

sides

2-sided

lower limit

22.1

upper limit

39.1

Notes
[204] - Analysis refers to patients' assessments.
[205] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

2nd FU visit: 'Excellent' tolerability (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[206]

P-value

< 0.0001 ^[207]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

28.3

Confidence interval

level

95%

sides

2-sided

lower limit

19.7

upper limit

36.8

Notes
[206] - Analysis refers to physicians' assessments.
[207] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

Term. visit: 'Excellent' tolerability (patient)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[208]

P-value

< 0.0001 ^[209]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

39.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

47.9

Notes
[208] - Analysis refers to patients' assessments.
[209] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

Term. visit: 'Excellent' tolerability (physician)

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [ITT analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[210]

P-value

< 0.0001 ^[211]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

29.3

upper limit

46.4

Notes
[210] - Analysis refers to physicians' assessments.
[211] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly higher fraction of patients with 'excellent' tolerability of treatment in IFC compared to ST arm [ITT analysis set].

Other pre-specified: Present complaints of upper respiratory tract infection: Fever, mucosal hyperaemia, nasal breathing impairment

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End point title

Present complaints of upper respiratory tract infection: Fever, mucosal hyperaemia, nasal breathing impairment

End point description

Presence of individual URTI symptoms fever, mucosal hyperaemia [MucHyp] and nasal breathing impairment [NBImp] has been assessed by physician at each visit.

End point type

Other pre-specified

End point timeframe

1st FU visit, 2nd FU visit and termination visit

End point values	IFC arm [PP analysis set]	ST arm [ITT analysis set]
Number of subjects analysed	261 ^[212]	256 ^[213]
Units: patients
1st FU V.: Presence of fever	46	80
1st FU V.: Absence of fever	215	176
1st FU V.: missing data: fever	0	0
2nd FU V.: Presence of fever	8	16
2nd FU V.: Absence of fever	251	235
2nd FU V.: missing data: fever	0	1
Term. V.: Presence of fever	5	8
Term. V.: Absence of fever	251	238
Term. V.: missing data: fever	0	0
1st FU V.: Presence of MucHyp	188	208
1st FU V.: Absence of MucHyp	73	48
1st FU V.: missing data: MucHyp	0	0
2nd FU V.: Presence of MucHyp	55	96
2nd FU V.: Absence of MucHyp	204	155
2nd FU V.: missing data: MucHyp	0	1
Term. V.: Presence of MucHyp	12	16
Term. V.: Absence of MucHyp	244	230
Term. V.: missing data: MucHyp	0	0
1st FU V.: Presence of NBImp	169	208
1st FU V.: Absence of NBImp	92	48
1st FU V.: missing data: NBImp	0	0
2nd FU V.: Presence of NBImp	68	111
2nd FU V.: Absence of NBImp	191	140
2nd FU V.: missing data: NBImp	0	1
Term. V.: Presence of NBImp	23	26
Term. V.: Absence of NBImp	233	220
Term. V.: missing data: NBImp	0	0

Notes
[212] - Total assessments per visit: 1st FU: N=261 2ndFU: N=259 Termination: N=256
[213] - Total assessments per visit: 1st FU: N=256 2ndFU: N=252 Termination: N=246

1st FU: Presence of fever

Statistical analysis description

Explorative analysis of URTI complaint's presence as assessed by physical examination at each visit [ITT analysis set]. Binary categorization "absence" vs. "presence" with respect to symptom is considered. Presented values for risk difference are related to the difference in symptom's presence between treatments taking into account the direction 'IFC - ST'.

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[214]

P-value

= 0.0003 ^[215]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-13.6

Confidence interval

level

95%

sides

2-sided

lower limit

-21.3

upper limit

-5.9

Notes
[214] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
[215] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with presence of fever (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].

2nd FU: Presence of fever

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[216]

P-value

= 0.0798

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

0.8

Notes
[216] - Analysis refers to physicians' physical examination assessments not taking missing values into account.

Term.visit: Presence of fever

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[217]

P-value

= 0.3597

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

1.9

Notes
[217] - Analysis refers to physicians' physical examination assessments not taking missing values into account.

1st FU: Presence of mucosal hyperaemia

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[218]

P-value

= 0.0133 ^[219]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-9.2

Confidence interval

level

95%

sides

2-sided

lower limit

-16.9

upper limit

-1.6

Notes
[218] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
[219] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present mucosal hyperaemia (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].

2nd FU: Presence of mucosal hyperaemia

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[220]

P-value

< 0.0001 ^[221]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-17

Confidence interval

level

95%

sides

2-sided

lower limit

-25.2

upper limit

-8.8

Notes
[220] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
[221] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present mucosal hyperaemia (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].

Term.visit: Presence of mucosal hyperaemia

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[222]

P-value

= 0.3753

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

2.6

Notes
[222] - Analysis refers to physicians' physical examination assessments not taking missing values into account.

1st FU: Presence of nasal breathing impairment

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[223]

P-value

< 0.0001 ^[224]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-16.5

Confidence interval

level

95%

sides

2-sided

lower limit

-24.4

upper limit

-8.6

Notes
[223] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
[224] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present nasal breathing impairment(assessed by physical examination) in IFC compared to ST arm [ITT analysis set].

2nd FU: Presence of nasal breathing impairment

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[225]

P-value

< 0.0001 ^[226]

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-18

Confidence interval

level

95%

sides

2-sided

lower limit

-26.5

upper limit

-9.4

Notes
[225] - Analysis refers to physicians' physical examination assessments not taking missing values into account.
[226] - A statistically significant difference (at alpha level 0.05) is concluded, indicating a significantly lower fraction of patients with present nasal breathing impairment (assessed by physical examination) in IFC compared to ST arm [ITT analysis set].

Term.visit: Presence of nasal breathing impairment

Statistical analysis description

Comparison groups

ST arm [ITT analysis set] v IFC arm [PP analysis set]

Number of subjects included in analysis

517

Analysis specification

Pre-specified

Analysis type

other ^[227]

P-value

= 0.5498

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-7.2

upper limit

Notes
[227] - Analysis refers to physicians' physical examination assessments not taking missing values into account.

Adverse events

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Timeframe for reporting adverse events

Whole study period.

Adverse event reporting additional description

Adverse event [AE] monitoring has been done at all post-baseline visits and during both FU calls. All AEs, irrespective of severity, seriousness and relationship to study drug, had to be monitored by the investigator until they had satisfactorily subsided or stabilised to such an extent that further marked improvement was not longer to be expected.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

ST [SAF]

Reporting group description

The control group "ST" was treated only with symptomatic medication on-demand.

Reporting group title

IFC [SAF]

Reporting group description

The test group “IFC” received 7 days of treatment with Influcid tablets (day 1 - day 7) additionally to on-demand symptomatic treatment

Serious adverse events	ST [SAF]	IFC [SAF]
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 258 (0.00%)	0 / 265 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	ST [SAF]	IFC [SAF]
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 258 (5.81%)	13 / 265 (4.91%)
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	3 / 258 (1.16%)	4 / 265 (1.51%)
occurrences all number	3	5
Vomiting
subjects affected / exposed	0 / 258 (0.00%)	3 / 265 (1.13%)
occurrences all number	0	3
Nausea
subjects affected / exposed	3 / 258 (1.16%)	1 / 265 (0.38%)
occurrences all number	3	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 258 (0.39%)	3 / 265 (1.13%)
occurrences all number	1	3
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 258 (0.39%)	3 / 265 (1.13%)
occurrences all number	1	3
Infections and infestations
Bronchitis
subjects affected / exposed	7 / 258 (2.71%)	1 / 265 (0.38%)
occurrences all number	7	1

More information

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Were there any global substantial amendments to the protocol? Yes

14 Oct 2010

Amendment 1 corresponds to the implementation of protocol final V2.0 from 14OCT2010 which included the changes to the original protocol (final V1.0 from 28JUN2010) required by the ethics committee of the Bavarian State Medical Association (Germany). In addition the patient informed consents for adults, legal representatives and children were updated and a patient informed consent for adolescents was implemented in Germany.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Efficacy, safety and tolerability of Influcid tablets in patients (1 to 65 years old) suffering from upper respiratory tract infections with flu-like symptoms. A randomized, international, multicenter, controlled clinical trial.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Fraction of patients with symptom alleviation at day 4 of the study

Primary: Fraction of patients with symptom alleviation at day 4 of the study

Secondary: Time to symptom alleviation

Secondary: Time to symptom alleviation

Secondary: Fraction of patients with symptom alleviation as defined for primary objective at study day 2, 3, 5, etc. until end of study

Secondary: Fraction of patients with symptom alleviation as defined for primary objective at study day 2, 3, 5, etc. until end of study

Secondary: Fraction of patients with maintenance of symptom alleviation as defined for primary objective until end of study

Secondary: Fraction of patients with maintenance of symptom alleviation as defined for primary objective until end of study

Secondary: Time to return to normal daily activity [investigators' assessment]

Secondary: Time to return to normal daily activity [investigators' assessment]

Secondary: Resolution of individual symptoms (analysed via WURSS-21)

Secondary: Resolution of individual symptoms (analysed via WURSS-21)

Secondary: Time to resolution of individual symptoms (analysed via diary WURSS-21)

Secondary: Time to resolution of individual symptoms (analysed via diary WURSS-21)

Secondary: Area under the curve (AUC) describing severity and course of the infection

Secondary: Area under the curve (AUC) describing severity and course of the infection

Secondary: Total amount and amount per day of paracetamol consumption

Secondary: Total amount and amount per day of paracetamol consumption

Secondary: Total amount and amount per day of ambroxol consumption

Secondary: Total amount and amount per day of ambroxol consumption

Secondary: Total amount and amount per day of oxymetazoline consumption

Secondary: Total amount and amount per day of oxymetazoline consumption

Secondary: Duration of symptomatic medication consumption

Secondary: Duration of symptomatic medication consumption

Secondary: Fraction of patients who must be withdrawn from the study due to prohibited medication

Secondary: Fraction of patients who must be withdrawn from the study due to prohibited medication

Secondary: Treatment outcome according to integrative medicine outcomes scale (IMOS)

Secondary: Treatment outcome according to integrative medicine outcomes scale (IMOS)

Secondary: Satisfaction with treatment according to integrative medicine patient satisfaction scale [IMPSS]

Secondary: Satisfaction with treatment according to integrative medicine patient satisfaction scale [IMPSS]

Secondary: Patients’ / parents’ assessment of tolerability of treatment

Secondary: Patients’ / parents’ assessment of tolerability of treatment

Other pre-specified: Present complaints of upper respiratory tract infection: Fever, mucosal hyperaemia, nasal breathing impairment

Other pre-specified: Present complaints of upper respiratory tract infection: Fever, mucosal hyperaemia, nasal breathing impairment

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Efficacy, safety and tolerability of Influcid tablets in patients (1 to 65 years old) suffering from upper respiratory tract infections with flu-like symptoms. A randomized, international, multicenter, controlled clinical trial.