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Clinical Trial Results:
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Dose-ranging Study of Vapendavir in Moderate to Severe Asthmatic Adults with Symptomatic Human Rhinovirus Infection.

Summary
EudraCT number	2014-001785-95
Trial protocol	CZ BG PL
Global end of trial date	09 Dec 2016

Results information
Results version number	v1(current)
This version publication date	01 Jan 2019
First version publication date	01 Jan 2019
Other versions

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

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Trial information

Top of page

Sponsor protocol code

BTA798-203

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Biota Pharma Europe Limited

Sponsor organisation address

2500 Northwinds Parkway, Suite 100, Alpharetta, United States, 30009

Public contact

VP, Clinical Development, Biota Pharmaceuticals, Inc., +1 6782213343, a.barry@biotapharma.com

Scientific contact

VP, Clinical Development, Biota Pharmaceuticals, Inc., +1 6782213343, a.barry@biotapharma.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?

Analysis stage

Final

Date of interim/final analysis

02 Feb 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

09 Dec 2016

Global end of trial reached?

Yes

Global end of trial date

09 Dec 2016

Was the trial ended prematurely?

Main objective of the trial

To evaluate the effect of vapendavir on asthma control following HRV infection, as measured by the Asthma Control Questionnaire (ACQ-6).

Protection of trial subjects

The study was performed in accordance with applicable regulatory and ethical guidelines including the Declaration of Helsinki and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (GCP), and any applicable national and local laws and regulations.

Background therapy

At least 264 µg daily of fluticasone

Evidence for comparator

N/A

Actual start date of recruitment

02 Feb 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 265

Country: Number of subjects enrolled

Georgia: 9

Country: Number of subjects enrolled

Czech Republic: 44

Country: Number of subjects enrolled

Bulgaria: 77

Country: Number of subjects enrolled

Poland: 56

Country: Number of subjects enrolled

Romania: 13

Worldwide total number of subjects

464

EEA total number of subjects

190

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)

Adolescents (12-17 years)

Adults (18-64 years)

420

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was a multicenter trial that was conducted at approximately 60 sites among 6 Northern Hemisphere countries in North America and Central Europe.

Screening details

Patients with an established history of moderate to severe asthma and a history of losing asthma control as a result of upper respiratory tract infection (URTI) were screened up to 180 days prior to becoming symptomatic with a common cold infection.

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Blinding implementation details

Study drug (active and placebo) were identical in physical appearance. Unblinded bioanalytical analysis was only transferred to the blinded study team post database lock. Unblinding via the IWRS could only be performed by personnel with an appropriate level of access.

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo dose consists of applicable matching placebo capsules.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo dose consists of applicable matching placebo capsules.

264 mg BID vapendavir

Arm description

264 mg dose consists of 2x 132 mg capsules of vapendavir phosphate

Arm type

Experimental

Investigational medicinal product name

Vapendavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

264 mg BID PO vapendavir achieved with two 132 mg capsules and two matching placebo capsules at each intake for 7 days.

528 mg BID vapendavir

Arm description

264 mg dose consists of 4x 132 mg capsules of vapendavir phosphate

Arm type

Experimental

Investigational medicinal product name

Vapendavir

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

528 mg BID PO vapendavir achieved with four 132 capsules at each intake for 7 days

Number of subjects in period 1	Placebo	264 mg BID vapendavir	528 mg BID vapendavir
Started	156	153	155
Completed	155	141	150
Not completed	1	12	5
Consent withdrawn by subject	1	6	-
Physician decision	-	-	1
Adverse event, non-fatal	-	3	2
Lost to follow-up	-	1	2
Noncompliance with Study Protocol/Study Visits	-	1	-
Withdrawal of Informed Consent	-	1	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Placebo dose consists of applicable matching placebo capsules.

Reporting group title

264 mg BID vapendavir

Reporting group description

264 mg dose consists of 2x 132 mg capsules of vapendavir phosphate

Reporting group title

528 mg BID vapendavir

Reporting group description

264 mg dose consists of 4x 132 mg capsules of vapendavir phosphate

Reporting group values	Placebo	264 mg BID vapendavir	528 mg BID vapendavir	Total
Number of subjects	156	153	155	464
Age categorical
Units: Subjects
not recorded	156	153	155	464
Gender categorical
Units: Subjects
Not Reported	156	153	155	464

Subject analysis set title

Placebo

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

ITT-I: All patients in the ITT population who had laboratory-confirmed HRV infection (by either RVP [Day 1] or RT-PCR for either the NPS or TBM sample on any of Study Days 1, 3, 5, or 7). This was the primary efficacy population.

Subject analysis set title

264 mg BID

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

528 mg BID

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

Combined

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis sets values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects	57	54	57	111
Age categorical
Units: Subjects
not recorded	57	54	57	111
Age continuous
Units:
	( )	( )	( )	( )
Gender categorical
Units: Subjects
Not Reported	57	54	57	111

End points

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Reporting group title

Placebo

Reporting group description

Placebo dose consists of applicable matching placebo capsules.

Reporting group title

264 mg BID vapendavir

Reporting group description

264 mg dose consists of 2x 132 mg capsules of vapendavir phosphate

Reporting group title

528 mg BID vapendavir

Reporting group description

264 mg dose consists of 4x 132 mg capsules of vapendavir phosphate

Subject analysis set title

Placebo

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

264 mg BID

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

528 mg BID

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

Combined

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Primary: LS mean change from baseline to Study Day 14 in ACQ-6 total score

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End point title

LS mean change from baseline to Study Day 14 in ACQ-6 total score

End point description

The Least Square (LS) mean change from baseline (Study Day 1) to Study Day 14 in ACQ-6 total score

End point type

Primary

End point timeframe

From baseline (Study Day 1) to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: total score
least squares mean (standard error)	-0.94 ( 0.181 )	-0.75 ( 0.184 )	-0.79 ( 0.189 )	-0.77 ( 0.174 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.319 ^[1]

Method

ANCOVA

Confidence interval

Notes
[1] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.319 ^[2]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

0.8

Notes
[2] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.319 ^[3]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

1.5

Notes
[3] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region.

Secondary: Proportion of Patients with a moderate or severe asthma exacerbation

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End point title

Proportion of Patients with a moderate or severe asthma exacerbation

End point description

Proportion of patients with a moderate or severe asthma exacerbation within Study Day 1 to Study Day 14,

End point type

Secondary

End point timeframe

Within Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: Patients	12	14	10	24

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.563 ^[4]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[4] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.632 ^[5]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[5] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.942 ^[6]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[6] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Proportion of patients with a severe asthma exacerbation

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End point title

Proportion of patients with a severe asthma exacerbation

End point description

Proportion of patients with a severe asthma exacerbation within Study Day 1 to Study Day 14, inclusive

End point type

Secondary

End point timeframe

Within Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: Patients	1	2	4	6

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.533 ^[7]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[7] - The p-value corresponds to the test of no treatment based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.173 ^[8]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[8] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.265 ^[9]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[9] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: LS mean change from baseline to Study Day 7 in ACQ-6 total score

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End point title

LS mean change from baseline to Study Day 7 in ACQ-6 total score

End point description

The LS mean change from baseline to Study Day 7 in ACQ-6 total score

End point type

Secondary

End point timeframe

From baseline to Study Day 7

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	53	56	109
Units: Total Score
least squares mean (standard deviation)	-0.47 ( 0.177 )	-0.34 ( 0.179 )	-0.34 ( 0.184 )	-0.34 ( 0.169 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.471 ^[10]

Method

ANCOVA

Confidence interval

Notes
[10] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.471 ^[11]

Method

ANCOVA

Confidence interval

Notes
[11] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.471 ^[12]

Method

ANCOVA

Confidence interval

Notes
[12] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region

Secondary: Proportion of patients with ≥0.5 point reduction in ACQ-6 score

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End point title

Proportion of patients with ≥0.5 point reduction in ACQ-6 score

End point description

Proportion of patients with ≥0.5 point reduction in ACQ-6 score from baseline over the 28 days of the study

End point type

Secondary

End point timeframe

From baseline over 28 days of study

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: Patients	45	41	46	87

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.673 ^[13]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[13] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.814 ^[14]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[14] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.914 ^[15]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[15] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Proportion of patients with ≥0.5 point increase in ACQ-6 score

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End point title

Proportion of patients with ≥0.5 point increase in ACQ-6 score

End point description

Proportion of patients with ≥0.5 point increase in ACQ-6 score from baseline over the 28 days of the study

End point type

Secondary

End point timeframe

From baseline over the 28 days of the study

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: Patients	8	12	11	23

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267 ^[16]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[16] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.454 ^[17]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[17] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.292 ^[18]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[18] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Proportion of patients with a post-Study Day 1 ACQ-6 score of ≤1.5

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End point title

Proportion of patients with a post-Study Day 1 ACQ-6 score of ≤1.5

End point description

Proportion of patients with a post-Study Day 1 ACQ-6 score of ≤1.5

End point type

Secondary

End point timeframe

post-Study Day 1

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: Patients	41	36	38	74

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

264 mg BID v Placebo

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.526 ^[19]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[19] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.546 ^[20]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[20] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.482 ^[21]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[21] - The p-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Daily ß2-agonist use over Study Day 1 to Study Day 14

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End point title

Daily ß2-agonist use over Study Day 1 to Study Day 14

End point description

Daily ß2-agonist use over Study Day 1 to Study Day 14

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: ß-agonist uses
least squares mean (standard error)	1.86 ( 0.451 )	1.41 ( 0.455 )	1.65 ( 0.470 )	1.53 ( 0.432 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.783 ^[22]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

6.1

Notes
[22] - The p-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthma severity and geographical region. The p-value is from the model with the ranked response variable as dependent variables

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.783 ^[23]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

8.6

Notes
[23] - The p-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthma severity and geographical region. The p-value is from the model with the ranked response variable as dependent variables

Statistical Analysis - Combined vs Placbo

Comparison groups

Combined v Placebo

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.783 ^[24]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

8.6

Notes
[24] - The p-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthma severity and geographical region. The p-value is from the model with the ranked response variable as dependent variables

Secondary: Reliever free days

Top of page

End point title

Reliever free days

End point description

Reliever free days over Study Day 1 to Study Day 14

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: days
least squares mean (standard error)	6.8 ( 0.90 )	7.2 ( 0.91 )	7.5 ( 0.94 )	7.4 ( 0.86 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.961 ^[25]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[25] - The p-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthama severity and geographical region. The p-value is from the model with ranked response variable as the dependent variable

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.525 ^[26]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[26] - The p-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthama severity and geographical region. The p-value is from the model with ranked response variable as the dependent variable

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.525 ^[27]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[27] - The p-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthama severity and geographical region. The p-value is from the model with ranked response variable as the dependent variable

Secondary: Maximum fall in FEV1

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End point title

Maximum fall in FEV1

End point description

Maximum fall in clinic-based forced expiratory volume in 1 second (FEV1) during Study Day 1 to Study Day 14 as a percent of the Study Day 1 level

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	56	50	57	107
Units: Litres
least squares mean (standard error)	1.579 ( 5.2133 )	-4.780 ( 5.3190 )	-1.802 ( 5.4146 )	-3.291 ( 4.9958 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87 ^[28]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-36.98

upper limit

34.67

Notes
[28] - The p-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Study Day 1 pre-bronchodilator FEV1, and geographical region.

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87 ^[29]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-49.1

upper limit

47.92

Notes
[29] - The p-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthama severity, Study Day 1 pre-bronchodilator FEV1, and geographical region

Statistical Analysis - Combined vs Placbo

Comparison groups

Combined v Placebo

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87 ^[30]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-49.1

upper limit

47.92

Notes
[30] - The p-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Study Day 1 pre-bronchodilator FEV1, and geographical region.

Secondary: Maximum increase in clinical-based FEV1

Top of page

End point title

Maximum increase in clinical-based FEV1

End point description

Maximum increase in clinic-based FEV1 during Study Days 1 to Study Day 14 as a percent of the Study Day 1 level

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: Litres
least squares mean (standard error)	1.579 ( 5.2133 )	-4.780 ( 5.3190 )	-1.802 ( 5.4146 )	-3.291 ( 4.9958 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

264 mg BID v Placebo

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87 ^[31]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-36.98

upper limit

34.67

Notes
[31] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator FEV1, and geographical region.

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87 ^[32]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-49.1

upper limit

47.92

Notes
[32] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator FEV1, and geographical region.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87 ^[33]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-49.1

upper limit

47.92

Notes
[33] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator FEV1, and geographical region.

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Top of page

End point title

WURSS-21 daily change severity score averaged over the peak infection

End point description

WURSS-21 daily change severity score averaged over the peak infection Study Day 2 to Study Day 4

End point type

Secondary

End point timeframe

Study Day 2 to Study Day 4

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	56	50	57	107
Units: severity score
least squares mean (standard error)	-24.93 ( 5.169 )	-24.61 ( 5.232 )	-28.06 ( 5.431 )	-26.33 ( 4.976 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.73 ^[34]

Method

ANCOVA

Confidence interval

Notes
[34] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region. It is from the model with the ranked response variable as the dependent variable

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.73 ^[35]

Method

ANCOVA

Confidence interval

Notes
[35] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region. It is from the model with the ranked response variable as the dependent variable

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.73 ^[36]

Method

ANCOVA

Confidence interval

Notes
[36] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region. It is from the model with the ranked response variable as the dependent variable

Secondary: Time to alleviate WURSS-21 cold symptoms

Top of page

End point title

Time to alleviate WURSS-21 cold symptoms

End point description

Time to alleviation (hours) of WURSS-21 cold symptoms

End point type

Secondary

End point timeframe

Length of study

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	54	57	111
Units: hours
arithmetic mean (standard deviation)	9.1 ( 0.49 )	9.3 ( 0.51 )	8.2 ( 0.46 )	8.8 ( 0.34 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.212 ^[37]

Method

Regression, Cox

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[37] - The p-value for the test of no treatment difference was based on Cox Proportional Hazards model with covariates for asthma severity, gender, and geographical region.

Statistical Analysis - 528 mg BID vs Placbo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.212 ^[38]

Method

Regression, Cox

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[38] - The p-value for the test of no treatment difference was based on Cox Proportional Hazards model with covariates for asthma severity, gender, and geographical region.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.212 ^[39]

Method

Regression, Cox

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[39] - The p-value for the test of no treatment difference was based on Cox Proportional Hazards model with covariates for asthma severity, gender, and geographical region.

Secondary: Maximum fall in peak expiratory flow (PEF)

Top of page

End point title

Maximum fall in peak expiratory flow (PEF)

End point description

Maximum fall in clinic-based peak expiratory flow (PEF) during Study Day 1 to Study Day 14, as a percent of the Study Day 1 level

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	56	50	57	107
Units: L/min
least squares mean (standard error)	7.6 ( 5.89 )	-5.5 ( 5.99 )	2.7 ( 6.12 )	-1.4 ( 5.64 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.074 ^[40]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-32

upper limit

Notes
[40] - P-value for test of no treatment difference is based on analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator PEF and geographical region.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

528 mg BID v Placebo

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.074 ^[41]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-35

upper limit

Notes
[41] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator PEF, and geographical region.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.074 ^[42]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-35

upper limit

Notes
[42] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator PEF, and geographical region.

Secondary: Maximum fall in peak expiratoy flow (PEF), post-SABA level

Top of page

End point title

Maximum fall in peak expiratoy flow (PEF), post-SABA level

End point description

Maximum absolute fall in clinic-based peak expiratory (PEF) during Study Day 1 to Study Day 14 from Study Day 1, post-SABA level

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	50	57	107
Units: L/min
least squares mean (standard error)	-4.0 ( 14.87 )	-4.4 ( 15.19 )	6.0 ( 15.52 )	0.8 ( 14.30 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.762 ^[43]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

144

upper limit

658

Notes
[43] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 post-bronchodilator PEF, and geographical region.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.762 ^[44]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-76

upper limit

144

Notes
[44] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 post-bronchodilator PEF, and geographical region.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.762 ^[45]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-144

upper limit

144

Notes
[45] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 post-bronchodilator PEF, and geographical region.

Secondary: Maximum fall in FVC

Top of page

End point title

Maximum fall in FVC

End point description

Maximum fall in forced vital capacity (FVC) during the Study Day 1 to Study Day 14, as a percent of the Study Day 1 level

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	56	50	57	107
Units: Litres
least squares mean (standard error)	-0.854 ( 4.3693 )	-2.845 ( 4.4395 )	-1.931 ( 4.5456 )	-2.388 ( 4.1840 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.686 ^[46]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-31

upper limit

40.26

Notes
[46] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator FVC, and geographical region.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.686 ^[47]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-38.53

upper limit

38.78

Notes
[47] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator FVC, and geographical region.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.686 ^[48]

Method

ANCOVA

Confidence interval

level

95%

sides

2-sided

lower limit

-38.53

upper limit

40.26

Notes
[48] - P-value for test of no treatment difference is based on an analysis of covariance model with fixed effects for treatment, asthma severity, Day 1 pre-bronchodilator FVC, and geographical region.

Secondary: Proportion of patients with a ≥10% decline in FVC

Top of page

End point title

Proportion of patients with a ≥10% decline in FVC

End point description

Proportion of patients with a ≥10% decline from the Study Day 1 level in FVC at any time during Study Day 1 to Study Day 14

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	152	151	152	303
Units: Patients	34	35	36	71

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.877 ^[49]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[49] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

304

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.786 ^[50]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[50] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

455

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.798 ^[51]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[51] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Proportion of patients with a ≥10% increase in FVC

Top of page

End point title

Proportion of patients with a ≥10% increase in FVC

End point description

Proportion of patients with a ≥10% increase from the Study Day 1 level in FVC at any time during Study Day 1 to Study Day 14

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	152	151	152	303
Units: Patients	44	35	49	84

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.249 ^[52]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[52] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

304

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.534 ^[53]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[53] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

455

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.775 ^[54]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[54] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Proportion of patients with ≥10% decline in FEV1

Top of page

End point title

Proportion of patients with ≥10% decline in FEV1

End point description

Proportion of patients with a ≥10% decline from the Study Day 1 level in FEV1 at any time during Study Day 1 to Study Day 14

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	55	46	52	98
Units: Patients	18	15	16	31

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.988 ^[55]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[55] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.825 ^[56]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[56] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.886 ^[57]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[57] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Secondary: Proportion of patients with a ≥10% increase in FEV1

Top of page

End point title

Proportion of patients with a ≥10% increase in FEV1

End point description

Proportion of patients with a ≥10% increase from the Study Day 1 level in FEV1 at any time during Study Day 1 to Study Day 14

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 14

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	55	46	52	98
Units: Patients	21	15	14	29

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.568 ^[58]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[58] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.228 ^[59]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[59] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - Combined vs Placbo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.287 ^[60]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[60] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Secondary: LS mean change from baseline to Study Day 21 in ACQ-6 total score

Top of page

End point title

LS mean change from baseline to Study Day 21 in ACQ-6 total score

End point description

The LS mean change from baseline to Study Day 21 in ACQ-6 total score

End point type

Secondary

End point timeframe

Baseline to Study Day 21

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	51	56	107
Units: total score
least squares mean (standard error)	-1.03 ( 0.177 )	-0.66 ( 0.180 )	-0.82 ( 0.185 )	-0.74 ( 0.170 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02 ^[61]

Method

ANCOVA

Confidence interval

Notes
[61] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[62]

Method

ANCOVA

Confidence interval

Notes
[62] - p-value corresponds to pairwise comparisons of each active group versus placebo created from linear contrasts of the placebo model. Values are only presented if the test of treatment effect was significant at the 0.05 level

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.105 ^[63]

Method

ANCOVA

Confidence interval

Notes
[63] - p-value corresponds to pairwise comparisons of each active group versus placebo created from linear contrasts of the placebo model. Values are only presented if the test of treatment effect was significant at the 0.05 level

Secondary: LS mean change from baseline to Study Day 28 in ACQ-6 total score

Top of page

End point title

LS mean change from baseline to Study Day 28 in ACQ-6 total score

End point description

The LS mean change from baseline to Study Day 28 in ACQ-6 total score

End point type

Secondary

End point timeframe

Baseline to Study Day 28

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	48	56	104
Units: total score
least squares mean (standard error)	-1.13 ( 0.180 )	-0.95 ( 0.183 )	-0.91 ( 0.187 )	-0.93 ( 0.172 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.205 ^[64]

Method

ANCOVA

Confidence interval

Notes
[64] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.205 ^[65]

Method

ANCOVA

Confidence interval

Notes
[65] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

161

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.205 ^[66]

Method

ANCOVA

Confidence interval

Notes
[66] - The p-value corresponds to the test of treatment effect from an ANCOVA with fixed effects for treatment, asthma severity, baseline ACQ-6 score, and geographical region.

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Top of page

End point title

WURSS-21 daily change severity score averaged over the peak infection

End point description

WURSS-21 daily change severity score averaged over the peak infectionStudy Day 3 to Study Day 5

End point type

Secondary

End point timeframe

Study Day 3 to Study Day 5

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	50	57	107
Units: severity score
least squares mean (standard error)	-37.15 ( 5.835 )	-35.04 ( 5.913 )	-40.43 ( 6.136 )	-37.74 ( 5.622 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.531 ^[67]

Method

ANCOVA

Confidence interval

Notes
[67] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region. It is from the model with the ranked response variable as the dependent variable

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.531 ^[68]

Method

ANCOVA

Confidence interval

Notes
[68] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region. It is from the model with the ranked response variable as the dependent variable

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.531 ^[69]

Method

ANCOVA

Confidence interval

Notes
[69] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region. It is from the model with the ranked response variable as the dependent variable

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Top of page

End point title

WURSS-21 daily change severity score averaged over the peak infection

End point description

WURSS-21 daily change severity score averaged over the peak infection Study Day 2 to Study Day 7

End point type

Secondary

End point timeframe

Study Day 2 to Study Day 7

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	57	50	57	107
Units: severity score
least squares mean (standard error)	-34.49 ( 5.578 )	-33.55 ( 5.653 )	-38.31 ( 5.866 )	-35.93 ( 5.374 )

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

264 mg BID v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.468 ^[70]

Method

ANCOVA

Confidence interval

Notes
[70] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

528 mg BID v Placebo

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.468 ^[71]

Method

ANCOVA

Confidence interval

Notes
[71] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.468 ^[72]

Method

ANCOVA

Confidence interval

Notes
[72] - The p-value for test of no treatment difference was based on an ANCOVA model with fixed effects for treatment, asthma severity, gender and geographical region.

Secondary: Proportion of patients with a ≥10% decline in FVC

Top of page

End point title

Proportion of patients with a ≥10% decline in FVC

End point description

Proportion of patients with a ≥10% decline from the Study Day 1 level in FVC at any time during Study Day 1 to Study Day 28

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 28

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	152	151	152	303
Units: Patients	41	47	46	93

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.436 ^[73]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[73] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

304

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.527 ^[74]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[74] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

455

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.411 ^[75]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[75] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Proportion of patients with a ≥10% increase in FVC

Top of page

End point title

Proportion of patients with a ≥10% increase in FVC

End point description

Proportion of patients with a ≥10% increase from the Study Day 1 level in FVC at any time during Study Day 1 to Study Day 28

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 28

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	152	151	152	303
Units: Patients	44	35	49	84

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

264 mg BID v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05 ^[76]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[76] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

304

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.999 ^[77]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[77] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

455

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.261 ^[78]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[78] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity.

Secondary: Proportion of patients with a ≥10% decline in FEV1

Top of page

End point title

Proportion of patients with a ≥10% decline in FEV1

End point description

Proportion of patients with a ≥10% decline from the Study Day 1 level in FEV1 at any time during Study Day 1 to Study Day 28

End point type

Secondary

End point timeframe

Study Day 1 to Study Day 28

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	55	46	52	98
Units: Patients	20	20	17	37

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.474 ^[79]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[79] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.681 ^[80]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[80] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.875 ^[81]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[81] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Secondary: Proportion of patients with ≥10 increase in FEV1

Top of page

End point title

Proportion of patients with ≥10 increase in FEV1

End point description

Proportion of patients with a ≥10% increase from the Study Day 1 level in FEV1 at any time during Study Day 1 to Study Day 28

End point type

Secondary

End point timeframe

Study Day 1 to Study 28

End point values	Placebo	264 mg BID	528 mg BID	Combined
Number of subjects analysed	55	46	52	98
Units: Patients	24	16	16	32

Statistical Analysis - 264 mg BID vs Placebo

Comparison groups

Placebo v 264 mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.372 ^[82]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[82] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - 528 mg BID vs Placebo

Comparison groups

Placebo v 528 mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.18 ^[83]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[83] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Statistical Analysis - Combined vs Placebo

Comparison groups

Placebo v Combined

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.183 ^[84]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[84] - P-value corresponds to the test of no treatment difference based on a Cochran-Mantel-Haenszel test stratified by asthma severity

Adverse events

Top of page

Timeframe for reporting adverse events

From initiation of study drug on Study Day 1 up to and including the final follow-up telephone call on Study Day 35

Adverse event reporting additional description

For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

Placebo

Reporting group description

Placebo dose consists of applicable matching placebo capsules.

Reporting group title

264 mg BID vapendavir

Reporting group description

264 mg dose consists of 2x 132 mg capsules of vapendavir phosphate

Reporting group title

528 mg BID vapendavir

Reporting group description

528 mg dose consists of 4x 132 mg capsules of vapendavir phosphate

Reporting group title

Combined

Reporting group description

Serious adverse events	Placebo	264 mg BID vapendavir	528 mg BID vapendavir	Combined
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	1 / 152 (0.66%)	2 / 303 (0.66%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Gastrointestinal disorders
Gastroenteritis viral
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
Additional description: Mild
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	264 mg BID vapendavir	528 mg BID vapendavir	Combined
Total subjects affected by non serious adverse events
subjects affected / exposed	60 / 151 (39.74%)	77 / 151 (50.99%)	71 / 152 (46.71%)	148 / 303 (48.84%)
Vascular disorders
Hypertension
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	1 / 151 (0.66%)	2 / 152 (1.32%)	3 / 303 (0.99%)
occurrences all number	1	1	2	3
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	1 / 152 (0.66%)	2 / 303 (0.66%)
occurrences all number	0	1	1	2
General disorders and administration site conditions
Chest discomfort
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	2 / 152 (1.32%)	2 / 303 (0.66%)
occurrences all number	0	0	2	2
Chest pain
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Drug withdrawal syndrome
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Fatigue
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	2 / 152 (1.32%)	2 / 303 (0.66%)
occurrences all number	0	0	2	2
Pyrexia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Reproductive system and breast disorders
Menstruation irregular
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Respiratory, thoracic and mediastinal disorders
Asthma
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	43 / 151 (28.48%)	48 / 151 (31.79%)	36 / 152 (23.68%)	84 / 303 (27.72%)
occurrences all number	43	48	36	84
Cough
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	3 / 151 (1.99%)	1 / 152 (0.66%)	4 / 303 (1.32%)
occurrences all number	0	3	1	4
Epistaxis
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	1 / 151 (0.66%)	2 / 152 (1.32%)	3 / 303 (0.99%)
occurrences all number	1	1	2	3
Nasal dryness
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Rhinitis allergic
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Sleep apnoea syndrome
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Wheezing
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Oropharyngeal pain
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Psychiatric disorders
Abnormal dreams
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Nightmare
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Panic attack
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Investigations
Alanine aminotransferase increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	1	0	1	1
Aspartate aminotransferase increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	1	0	1	1
Blood creatine increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Blood glucose increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	2 / 151 (1.32%)	1 / 151 (0.66%)	1 / 152 (0.66%)	2 / 303 (0.66%)
occurrences all number	2	1	1	2
Blood pressure increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Blood thyroid stimulating hormone increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Blood urea increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Electrocardiogram abnormal
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Electrocardiogram QT prolonged
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Electrocardiogram T wave inversion
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Gamma-glutamyltransferase increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Haematocrit increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Haemoglobin increased
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
White blood cell count increased
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Injury, poisoning and procedural complications
Arthropod bite
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	2 / 151 (1.32%)	0 / 152 (0.00%)	2 / 303 (0.66%)
occurrences all number	0	2	0	2
Contusion
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	1	0	0	1
Joint dislocation
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Joint injury
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Laceration
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Spinal column injury
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Cardiac disorders
Atrial flutter
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Bundle branch block right
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Palpitations
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Tachycardia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Nervous system disorders
Anosmia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Disturbance in attention
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Dizziness
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	1	0	1	1
Dysgeusia
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Headache
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	5 / 151 (3.31%)	7 / 152 (4.61%)	12 / 303 (3.96%)
occurrences all number	1	5	7	12
Blood and lymphatic system disorders
Eosinophilia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Leukopenia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Lymphadenopathy
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Neutropenia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Ear and labyrinth disorders
Ear pain
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Gastrointestinal disorders
Abdominal discomfort
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	2 / 152 (1.32%)	2 / 303 (0.66%)
occurrences all number	0	0	2	2
Abdominal pain
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Abdominal pain upper
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	3 / 152 (1.97%)	3 / 303 (0.99%)
occurrences all number	0	0	3	3
Constipation
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Dental caries
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Diarrhoea
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	2 / 151 (1.32%)	1 / 151 (0.66%)	2 / 152 (1.32%)	3 / 303 (0.99%)
occurrences all number	2	1	2	3
Flatulence
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Mouth haemorrhage
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Nausea
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	2 / 151 (1.32%)	3 / 152 (1.97%)	5 / 303 (1.65%)
occurrences all number	0	2	3	5
Umbilical hernia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Vomiting
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	2 / 152 (1.32%)	2 / 303 (0.66%)
occurrences all number	1	0	2	2
Skin and subcutaneous tissue disorders
Hyperhidrosis
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Rash papular
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Renal and urinary disorders
Nephrolithiasis
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Back pain
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	5 / 151 (3.31%)	0 / 152 (0.00%)	5 / 303 (1.65%)
occurrences all number	1	5	0	5
Muscle spasms
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Tendonitis
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Infections and infestations
Bartholin's abscess
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Bronchitis
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	3 / 152 (1.97%)	3 / 303 (0.99%)
occurrences all number	0	0	3	3
Bronchitis bacterial
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	1 / 151 (0.66%)	0 / 151 (0.00%)	0 / 152 (0.00%)	0 / 303 (0.00%)
occurrences all number	1	0	0	0
Candida infection
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Eye infection
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Gastroenteritis viral
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Influenza
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Lower respiratory tract infection viral
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	0 / 152 (0.00%)	1 / 303 (0.33%)
occurrences all number	0	1	0	1
Nasopharyngitis
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	2 / 151 (1.32%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	2	0	1	1
Sinusitis
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	1 / 152 (0.66%)	2 / 303 (0.66%)
occurrences all number	0	1	1	2
Sputum purulent
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1
Upper respiratory tract infection
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	3 / 151 (1.99%)	6 / 151 (3.97%)	3 / 152 (1.97%)	9 / 303 (2.97%)
occurrences all number	3	6	3	9
Urinary tract infection
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	2 / 151 (1.32%)	3 / 151 (1.99%)	2 / 152 (1.32%)	5 / 303 (1.65%)
occurrences all number	2	3	2	5
Metabolism and nutrition disorders
Decreased appetite
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	1 / 151 (0.66%)	1 / 152 (0.66%)	2 / 303 (0.66%)
occurrences all number	0	1	1	2
Hyperphosphataemia
Additional description: For patients who experienced the same coded event more than once, the greatest severity was presented within a treatment.
subjects affected / exposed	0 / 151 (0.00%)	0 / 151 (0.00%)	1 / 152 (0.66%)	1 / 303 (0.33%)
occurrences all number	0	0	1	1

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Were there any global substantial amendments to the protocol? No

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: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Dose-ranging Study of Vapendavir in Moderate to Severe Asthmatic Adults with Symptomatic Human Rhinovirus Infection.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: LS mean change from baseline to Study Day 14 in ACQ-6 total score

Primary: LS mean change from baseline to Study Day 14 in ACQ-6 total score

Secondary: Proportion of Patients with a moderate or severe asthma exacerbation

Secondary: Proportion of Patients with a moderate or severe asthma exacerbation

Secondary: Proportion of patients with a severe asthma exacerbation

Secondary: Proportion of patients with a severe asthma exacerbation

Secondary: LS mean change from baseline to Study Day 7 in ACQ-6 total score

Secondary: LS mean change from baseline to Study Day 7 in ACQ-6 total score

Secondary: Proportion of patients with ≥0.5 point reduction in ACQ-6 score

Secondary: Proportion of patients with ≥0.5 point reduction in ACQ-6 score

Secondary: Proportion of patients with ≥0.5 point increase in ACQ-6 score

Secondary: Proportion of patients with ≥0.5 point increase in ACQ-6 score

Secondary: Proportion of patients with a post-Study Day 1 ACQ-6 score of ≤1.5

Secondary: Proportion of patients with a post-Study Day 1 ACQ-6 score of ≤1.5

Secondary: Daily ß2-agonist use over Study Day 1 to Study Day 14

Secondary: Daily ß2-agonist use over Study Day 1 to Study Day 14

Secondary: Reliever free days

Secondary: Reliever free days

Secondary: Maximum fall in FEV1

Secondary: Maximum fall in FEV1

Secondary: Maximum increase in clinical-based FEV1

Secondary: Maximum increase in clinical-based FEV1

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Secondary: Time to alleviate WURSS-21 cold symptoms

Secondary: Time to alleviate WURSS-21 cold symptoms

Secondary: Maximum fall in peak expiratory flow (PEF)

Secondary: Maximum fall in peak expiratory flow (PEF)

Secondary: Maximum fall in peak expiratoy flow (PEF), post-SABA level

Secondary: Maximum fall in peak expiratoy flow (PEF), post-SABA level

Secondary: Maximum fall in FVC

Secondary: Maximum fall in FVC

Secondary: Proportion of patients with a ≥10% decline in FVC

Secondary: Proportion of patients with a ≥10% decline in FVC

Secondary: Proportion of patients with a ≥10% increase in FVC

Secondary: Proportion of patients with a ≥10% increase in FVC

Secondary: Proportion of patients with ≥10% decline in FEV1

Secondary: Proportion of patients with ≥10% decline in FEV1

Secondary: Proportion of patients with a ≥10% increase in FEV1

Secondary: Proportion of patients with a ≥10% increase in FEV1

Secondary: LS mean change from baseline to Study Day 21 in ACQ-6 total score

Secondary: LS mean change from baseline to Study Day 21 in ACQ-6 total score

Secondary: LS mean change from baseline to Study Day 28 in ACQ-6 total score

Secondary: LS mean change from baseline to Study Day 28 in ACQ-6 total score

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Secondary: WURSS-21 daily change severity score averaged over the peak infection

Secondary: Proportion of patients with a ≥10% decline in FVC

Secondary: Proportion of patients with a ≥10% decline in FVC

Secondary: Proportion of patients with a ≥10% increase in FVC

Secondary: Proportion of patients with a ≥10% increase in FVC

Secondary: Proportion of patients with a ≥10% decline in FEV1

Secondary: Proportion of patients with a ≥10% decline in FEV1

Secondary: Proportion of patients with ≥10 increase in FEV1

Secondary: Proportion of patients with ≥10 increase in FEV1

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Dose-ranging Study of Vapendavir in Moderate to Severe Asthmatic Adults with Symptomatic Human Rhinovirus Infection.