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Clinical Trial Results:
A 6-month, Randomised, Double-blind, Placebo-controlled,Multi-centre, Parallel-group, Phase II Study with an Optional Safety Extension Treatment Period up to 6 months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma

Summary
EudraCT number	2012-001869-33
Trial protocol	GB DE CZ HU PL SK BG
Global end of trial date	19 Dec 2014

Results information
Results version number	v1(current)
This version publication date	21 Feb 2016
First version publication date	21 Feb 2016
Other versions

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

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Trial information

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Sponsor protocol code

D3551C00001

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

AstraZeneca

Sponsor organisation address

Pepparedsleden 1, Mölndal, Sweden, SE-431 83

Public contact

Bengt Larsson, AstraZeneca, SE-431 83 +46 31 7064277, bengt.larsson@astrazeneca.com

Scientific contact

Paul O’Byrne, St Joseph’s Healthcare, L8N 4A6 9055259140-33694, obyrnep@mcmaster.ca

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

19 Dec 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Dec 2014

Global end of trial reached?

Yes

Global end of trial date

19 Dec 2014

Was the trial ended prematurely?

Main objective of the trial

To determine the efficacy of 3 different doses of AZD5069 compared with placebo on the rate of severe asthma exacerbations over 6 months in adults with uncontrolled persistent asthma, despite treatment with medium to high dose ICS (≥fluticasone 500 μg or the equivalent daily) and LABA

Protection of trial subjects

This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) and applicable regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological Samples.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Nov 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 121

Country: Number of subjects enrolled

Poland: 114

Country: Number of subjects enrolled

Russian Federation: 87

Country: Number of subjects enrolled

Ukraine: 65

Country: Number of subjects enrolled

Hungary: 55

Country: Number of subjects enrolled

Romania: 50

Country: Number of subjects enrolled

Mexico: 37

Country: Number of subjects enrolled

Slovakia: 36

Country: Number of subjects enrolled

Germany: 30

Country: Number of subjects enrolled

Czech Republic: 29

Country: Number of subjects enrolled

South Africa: 11

Country: Number of subjects enrolled

Canada: 5

Worldwide total number of subjects

640

EEA total number of subjects

435

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)

544

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

First patient enrolled: 27 November 2012 . Last patient last visit: 27 August 2014. Twelve centres across 12 countries participated in this study: Denmark (4), Germany (13), Poland (6),Russia (14), Sweden(13)and United Kingdom (5)

Screening details

1146 patients enrolled in the study of which 640 were randomised, the remaining 506 patients were not randomised since they did not fulfilled all the inclusion conditions.

Period 1 title

Overrall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

AZD 5069 5mg

Arm description

Arm type

Experimental

Investigational medicinal product name

AZD 5069

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

5mg capsule BID

AZD 5069 15 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

AZD 5069

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

capsule 15mg, twice a day

AZD5069 45mg

Arm description

Arm type

Experimental

Investigational medicinal product name

AZD 5069

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Capsules twice a day

Placebo

Arm description

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

capsule to match AZD5069

Number of subjects in period 1	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Started	160	156	162	162
Completed	145	143	145	151
Not completed	15	13	17	11
Adverse event, serious fatal	-	-	1	-
Eligibility criteria not fulfilled	6	3	2	3
Subject decision	6	5	8	4
Adverse event, non-fatal	-	2	5	4
Development of study specific withdrawal criteria	1	-	1	-
unknown reason for study withdrawn	1	1	-	-
Protocol deviation	1	2	-	-

Baseline characteristics

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Reporting group title

AZD 5069 5mg

Reporting group description

Reporting group title

AZD 5069 15 mg

Reporting group description

Reporting group title

AZD5069 45mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo	Total
Number of subjects	160	156	162	162	640
Age Categorical
Units: Subjects
≥18 - <50	64	57	68	48	237
≥50 - <65	72	79	74	82	307
≥65	24	20	20	32	96
Age Continuous
Units: years
arithmetic mean (standard deviation)	53 ( 11.5 )	52 ( 12.7 )	51 ( 11.6 )	54 ( 11.1 )	-
Gender Categorical
Units: Subjects
Female	104	113	107	120	444
Male	56	43	55	42	196

Subject analysis set title

Full analysis set

Subject analysis set type

Full analysis

Subject analysis set description

All patients randomised to investigational product were included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients were analysed according to their randomised investigational product irrespective of whether or not they prematurely discontinued investigational product or administered the incorrect treatment. Patients who withdrew consent to participate in the study were included up to the date of their study termination.

Subject analysis sets values	Full analysis set
Number of subjects	640
Age Categorical
Units: Subjects
≥18 - <50	237
≥50 - <65	307
≥65	96
Age Continuous
Units: years
arithmetic mean (standard deviation)	52 ( 11.8 )
Gender Categorical
Units: Subjects
Female
Male

End points

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Reporting group title

AZD 5069 5mg

Reporting group description

Reporting group title

AZD 5069 15 mg

Reporting group description

Reporting group title

AZD5069 45mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Full analysis set

Subject analysis set type

Full analysis

Subject analysis set description

Primary: number of severe exacerbations over 6 months

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End point title

number of severe exacerbations over 6 months

End point description

End point type

Primary

End point timeframe

6 months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	161	159
Units: number
number (not applicable)	28	33	35	25

Analysis of the rate of severe exacerbations

Statistical analysis description

Primary Analysis Model: Rates, rate ratios and p-values are from a Poisson regression analysis with treatment, OCS use at baseline (yes or no),geographical region and FEV1 pre-bronchodilator at baseline included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.119

Method

poission regression

Parameter type

Risk ratio (RR)

Point estimate

1.56

Confidence interval

level

90%

sides

2-sided

lower limit

0.98

upper limit

2.49

Analysis of the rate of severe exacerbations

Statistical analysis description

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.141

Method

possion regression

Parameter type

Risk ratio (RR)

Point estimate

1.53

Confidence interval

level

90%

sides

2-sided

lower limit

0.95

upper limit

2.46

Analysis of the rate of severe exacerbations

Statistical analysis description

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.397

Method

possion resgrssion

Parameter type

Risk ratio (RR)

Point estimate

1.29

Confidence interval

level

90%

sides

2-sided

lower limit

0.79

upper limit

2.11

Primary: total number of days of severe exacerbation

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End point title

total number of days of severe exacerbation

End point description

End point type

Primary

End point timeframe

over 6 months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	161	159
Units: days
number (not applicable)	255	271	291	220

total number of days of severe exacerbation

Statistical analysis description

Estimates, ratios and p-values are from a negative binomial regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.111

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

1.64

Confidence interval

level

90%

sides

2-sided

lower limit

0.98

upper limit

2.74

total number of days of severe exacerbation

Statistical analysis description

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.191

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

1.52

Confidence interval

level

90%

sides

2-sided

lower limit

0.9

upper limit

2.58

total number of days of severe exacerbation

Statistical analysis description

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.123

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

1.62

Confidence interval

level

90%

sides

2-sided

lower limit

0.97

upper limit

2.7

Primary: Patients experiencing one or more severe exacerbations

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End point title

Patients experiencing one or more severe exacerbations

End point description

End point type

Primary

End point timeframe

over 6 months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	161	159
Units: paticipents
number (not applicable)	23	26	28	21

experiencing one or more severe exacerbations

Statistical analysis description

logistic regression analysis with treatment, OCS use at baseline (yes or no) and geographical region included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.627

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.17

Confidence interval

level

90%

sides

2-sided

lower limit

0.68

upper limit

2.02

experiencing one or more severe exacerbations

Statistical analysis description

logistic regression analysis with treatment, OCS use at baseline (yes or no) and geographical region included in the model

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.296

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.4

Confidence interval

level

90%

sides

2-sided

lower limit

0.82

upper limit

2.38

experiencing one or more severe exacerbations

Statistical analysis description

logistic regression analysis with treatment, OCS use at baseline (yes or no) and geographical region included in the model

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.261

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.43

Confidence interval

level

90%

sides

2-sided

lower limit

0.85

upper limit

2.41

Secondary: event of asthma-specific hospital/intensive care unit (ICU)admissions

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End point title

event of asthma-specific hospital/intensive care unit (ICU)admissions

End point description

End point type

Secondary

End point timeframe

over 6 months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	161	159
Units: events
number (not applicable)	2	2	4	3

rate of asthma-specific hospital(ICU) admissions

Statistical analysis description

Poisson regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.806

Method

Poisson regression

Parameter type

Risk ratio (RR)

Point estimate

0.8

Confidence interval

level

90%

sides

2-sided

lower limit

0.17

upper limit

3.63

rate of asthma-specific hospital(ICU) admissions

Statistical analysis description

Poisson regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.844

Method

Poisson regression

Parameter type

Risk ratio (RR)

Point estimate

0.83

Confidence interval

level

90%

sides

2-sided

lower limit

0.18

upper limit

3.8

rate of asthma-specific hospital (ICU) admissions

Statistical analysis description

Poisson regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.563

Method

Poisson regression

Parameter type

Risk ratio (RR)

Point estimate

1.56

Confidence interval

level

90%

sides

2-sided

lower limit

0.44

upper limit

5.59

Secondary: total number of days of asthma-specific hospital /intensive care unit (ICU) admissions

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End point title

total number of days of asthma-specific hospital /intensive care unit (ICU) admissions

End point description

End point type

Secondary

End point timeframe

over 6 months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	161	159
Units: days
number (not applicable)	9	49	53	57

days of asthma-specific hospital (ICU) admissions

Statistical analysis description

negative binomial regression analysis with treatment,OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

0.02

Confidence interval

level

90%

sides

2-sided

lower limit

0.01

upper limit

0.07

days of asthma-specific hospital(ICU) admissions

Statistical analysis description

negative binomial regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

9.62

Confidence interval

level

90%

sides

2-sided

lower limit

5.06

upper limit

18.28

days of asthma-specific hospital(ICU) admissions

Statistical analysis description

negative binomial regression analysis with treatment,OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

6.37

Confidence interval

level

90%

sides

2-sided

lower limit

3.38

upper limit

11.97

Secondary: total number of days of oral corticosteroids (OCS) use due to worsening in asthma symptoms

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End point title

total number of days of oral corticosteroids (OCS) use due to worsening in asthma symptoms

End point description

End point type

Secondary

End point timeframe

over 6 months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	161	159
Units: days
number (not applicable)	247	227	266	183

days of OCS uses

Statistical analysis description

negative binomial regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.067

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

1.77

Confidence interval

level

90%

sides

2-sided

lower limit

1.06

upper limit

2.95

days of OCS use

Statistical analysis description

negative binomial regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

1.57

Confidence interval

level

90%

sides

2-sided

lower limit

0.92

upper limit

2.66

days of OCS use

Statistical analysis description

negative binomial regression analysis with treatment, OCS use at baseline (yes or no), geographical region and FEV1 pre-bronchodilator at baseline included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.172

Method

negative binomial regression

Parameter type

Risk ratio (RR)

Point estimate

1.54

Confidence interval

level

90%

sides

2-sided

lower limit

0.92

upper limit

2.58

Secondary: Pre-bronchodilator FEV1,measured before the morning administration of the investigational product

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End point title

Pre-bronchodilator FEV1,measured before the morning administration of the investigational product

End point description

Baseline is defined as the latest non-missing assessment prior to first dose (typically Visit 2, Randomisation). Treatment Period is defined as the average change from baseline across all available visits during the 6-month double-blindtreatment period regardless of whether or not a patient was actually taking IP at that visit.

End point type

Secondary

End point timeframe

Baseline and post treatment

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	155	151	159	158
Units: liter
least squares mean (standard error)	0.07 ( 0.037 )	0.08 ( 0.037 )	0.11 ( 0.036 )	0.09 ( 0.036 )

FEV1 pre-bronchodilator

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.601

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

90%

sides

2-sided

lower limit

-0.08

upper limit

0.04

FEV1 pre-bronchodilator

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.884

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

90%

sides

2-sided

lower limit

-0.06

upper limit

0.05

FEV1 pre-bronchodilator

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.47

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

90%

sides

2-sided

lower limit

-0.03

upper limit

0.08

Secondary: Post-bronchodilator FEV1,measured before the morning administration of the investigational product

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End point title

Post-bronchodilator FEV1,measured before the morning administration of the investigational product

End point description

Baseline is defined as the latest non-missing assessment prior to first dose (typically Visit 2, Randomisation).Treatment Period is defined as the average change from baseline across all available visits during the 6-month double-blindtreatment period regardless of whether or not a patient was actually taking IP at that visit.

End point type

Secondary

End point timeframe

Baseline and post treatment

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	152	147	154	153
Units: liters
least squares mean (standard error)	0 ( 0.029 )	0.03 ( 0.029 )	0.04 ( 0.028 )	0 ( 0.029 )

FEV1 post-bronchodilator

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.948

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

-0.04

upper limit

0.05

FEV1 post-bronchodilator

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.334

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

90%

sides

2-sided

lower limit

-0.02

upper limit

0.07

FEV1 post-bronchodilator

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

307

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.192

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

90%

sides

2-sided

lower limit

-0.01

upper limit

0.08

Secondary: Asthma control questionnaire [ACQ-5] score change from baseline to treatment period

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End point title

Asthma control questionnaire [ACQ-5] score change from baseline to treatment period

End point description

Treatment period is defined as the average of all available scores during the 6-month double-blind treatment period regardless of whether or not a patient was actually taking IP at that visit (excluding any unscheduled visits): the planned visits for completion were 1 month (visit 6), 2 months (visit 7), 3 months (visit 8), 4 months (visit 9) and 6 months (visit 11)

End point type

Secondary

End point timeframe

Baseline and post treatment

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	149	149	154	156
Units: score
least squares mean (standard error)	-0.64 ( 0.097 )	-0.66 ( 0.095 )	-0.68 ( 0.094 )	-0.7 ( 0.093 )

Asthma control questionnaire

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and baseline score included in the model. Negative values for a difference show AZD5069 to have a favourable outcome compared to placebo.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.476

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

90%

sides

2-sided

lower limit

-0.09

upper limit

0.22

Asthma control questionnaire

Statistical analysis description

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.678

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

90%

sides

2-sided

lower limit

-0.11

upper limit

0.19

Asthma control questionnaire

Statistical analysis description

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

310

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.766

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

90%

sides

2-sided

lower limit

-0.12

upper limit

0.18

Secondary: Asthma quality of life questionnaire (AQLQ[s]) overall and domain scores change from baseline to treatment period

Top of page

End point title

Asthma quality of life questionnaire (AQLQ[s]) overall and domain scores change from baseline to treatment period

End point description

End point type

Secondary

End point timeframe

Baseline and post treatment

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	145	145	152	153
Units: score
least squares mean (standard error)
overall score	0.52 ( 0.091 )	0.46 ( 0.089 )	0.5 ( 0.088 )	0.52 ( 0.089 )
Symptoms	0.63 ( 0.098 )	0.61 ( 0.096 )	0.65 ( 0.095 )	0.62 ( 0.096 )
Activity limitation	0.47 ( 0.093 )	0.39 ( 0.091 )	0.46 ( 0.09 )	0.49 ( 0.091 )
Emotional function	0.42 ( 0.106 )	0.36 ( 0.104 )	0.4 ( 0.103 )	0.41 ( 0.104 )

No statistical analyses for this end point

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

End point description

Treatment Period is defined as the percentage of symptom-free days across the entire 6-month double-blind treatment period for a patient (out of the total number number of days where data was available within the treatment period regardless of whether or not a patient was actually taking IP on that day)

End point type

Secondary

End point timeframe

Baseline and Day1 to Day 28

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	160	159
Units: percent
least squares mean (standard error)	1.2 ( 1.91 )	1.6 ( 1.87 )	-0.4 ( 1.85 )	1.1 ( 1.84 )

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.974

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.1

Confidence interval

level

90%

sides

2-sided

lower limit

-2.9

upper limit

3.1

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.797

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.5

Confidence interval

level

90%

sides

2-sided

lower limit

-2.5

upper limit

3.5

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.419

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.5

Confidence interval

level

90%

sides

2-sided

lower limit

-4.5

upper limit

1.5

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baselien and Day 29 to Day 56

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	152	148	158	155
Units: percent
least squares mean (standard error)	3.4 ( 2.81 )	2.6 ( 2.75 )	0.2 ( 2.73 )	3.1 ( 2.73 )

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

307

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.906

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.3

Confidence interval

level

90%

sides

2-sided

lower limit

-4.1

upper limit

4.7

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.83

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.6

Confidence interval

level

90%

sides

2-sided

lower limit

-5

upper limit

3.8

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.266

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.9

Confidence interval

level

90%

sides

2-sided

lower limit

-7.3

upper limit

1.4

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 57 to Day 84

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	149	146	155	154
Units: percent
least squares mean (standard error)	3 ( 3.05 )	4.3 ( 2.99 )	1.4 ( 2.96 )	4 ( 2.96 )

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.725

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1

Confidence interval

level

90%

sides

2-sided

lower limit

-5.8

upper limit

3.8

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.904

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.4

Confidence interval

level

90%

sides

2-sided

lower limit

-4.4

upper limit

5.1

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.374

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.6

Confidence interval

level

90%

sides

2-sided

lower limit

-7.3

upper limit

2.2

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 85 to End of 6 Months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	148	145	152	151
Units: percent
least squares mean (standard error)	3.9 ( 3.17 )	5.6 ( 3.11 )	2.6 ( 3.11 )	4.4 ( 3.09 )

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

299

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.884

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.4

Confidence interval

level

90%

sides

2-sided

lower limit

-5.4

upper limit

4.5

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

296

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.688

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.2

Confidence interval

level

90%

sides

2-sided

lower limit

-3.8

upper limit

6.2

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.557

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.8

Confidence interval

level

90%

sides

2-sided

lower limit

-6.7

upper limit

3.2

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and treatment period

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	160	159
Units: percent
least squares mean (standard error)	3.7 ( 2.61 )	4.2 ( 2.56 )	1.4 ( 2.53 )	3.3 ( 2.53 )

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.885

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.4

Confidence interval

level

90%

sides

2-sided

lower limit

-3.8

upper limit

4.5

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.721

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.9

Confidence interval

level

90%

sides

2-sided

lower limit

-3.2

upper limit

Percentage of symptom-free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.444

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.9

Confidence interval

level

90%

sides

2-sided

lower limit

-6

upper limit

2.2

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 1 to Day 28

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	160	159
Units: percent
least squares mean (standard error)	1.2 ( 1.74 )	1.7 ( 1.71 )	-1.1 ( 1.68 )	0.9 ( 1.68 )

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.3

Confidence interval

level

90%

sides

2-sided

lower limit

-2.5

upper limit

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.625

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.8

Confidence interval

level

90%

sides

2-sided

lower limit

-1.9

upper limit

3.6

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.214

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.1

Confidence interval

level

90%

sides

2-sided

lower limit

-4.8

upper limit

0.7

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 29 to Day 56

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	151	148	158	155
Units: percent
least squares mean (standard error)	2.7 ( 2.59 )	3.5 ( 2.54 )	-0.1 ( 2.51 )	2.8 ( 2.52 )

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.982

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

90%

sides

2-sided

lower limit

-4.1

upper limit

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.764

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.7

Confidence interval

level

90%

sides

2-sided

lower limit

-3.3

upper limit

4.8

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.239

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.9

Confidence interval

level

90%

sides

2-sided

lower limit

-6.9

upper limit

1.1

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 57 to Day 84

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	149	146	155	154
Units: percent
least squares mean (standard error)	3.2 ( 2.92 )	4.7 ( 2.87 )	0.9 ( 2.84 )	2.9 ( 2.84 )

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.904

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.3

Confidence interval

level

90%

sides

2-sided

lower limit

-4.2

upper limit

4.9

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.519

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.8

Confidence interval

level

90%

sides

2-sided

lower limit

-2.8

upper limit

6.4

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.466

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2

Confidence interval

level

90%

sides

2-sided

lower limit

-6.6

upper limit

2.5

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Bseline and Day 85 to End of 6 Months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	148	145	152	151
Units: percent
least squares mean (standard error)	3.9 ( 2.99 )	5.7 ( 2.93 )	1.4 ( 2.93 )	2.4 ( 2.91 )

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

299

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.604

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.5

Confidence interval

level

90%

sides

2-sided

lower limit

-3.2

upper limit

6.1

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

296

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.256

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.2

Confidence interval

level

90%

sides

2-sided

lower limit

-1.5

upper limit

7.9

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.71

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1

Confidence interval

level

90%

sides

2-sided

lower limit

-5.7

upper limit

3.6

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Treatment Period

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	160	159
Units: percent
least squares mean (standard error)	3.5 ( 2.46 )	4.4 ( 2.42 )	0.6 ( 2.38 )	2.3 ( 2.38 )

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.605

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.2

Confidence interval

level

90%

sides

2-sided

lower limit

-2.7

upper limit

5.1

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.359

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.2

Confidence interval

level

90%

sides

2-sided

lower limit

-1.7

upper limit

6.1

Percentage of asthma-control days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.475

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.7

Confidence interval

level

90%

sides

2-sided

lower limit

-5.5

upper limit

2.2

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

End point description

Treatment Period is defined as the percentage of rescue medication free days across the entire 6-month double-blind treatment period for a patient (out of the total number number of days where data was available within the treatment period regardless of whether or not a patient was actually taking IP on that day).

End point type

Secondary

End point timeframe

Baseline and Day 1 to Day 28

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	160	159
Units: percent
least squares mean (standard error)	6.8 ( 2.89 )	8.3 ( 2.84 )	4 ( 2.79 )	9.5 ( 2.8 )

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.324

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.7

Confidence interval

level

90%

sides

2-sided

lower limit

-7.3

upper limit

1.8

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.664

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.2

Confidence interval

level

90%

sides

2-sided

lower limit

-5.8

upper limit

3.4

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.047

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-5.5

Confidence interval

level

90%

sides

2-sided

lower limit

-10

upper limit

-1

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 29 to Day 56

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	150	148	158	155
Units: percent
least squares mean (standard error)	15.4 ( 3.84 )	17.6 ( 3.76 )	10.7 ( 3.71 )	9.5 ( 2.8 )

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.791

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1

Confidence interval

level

90%

sides

2-sided

lower limit

-7

upper limit

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.752

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.2

Confidence interval

level

90%

sides

2-sided

lower limit

-4.9

upper limit

7.2

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.114

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-5.7

Confidence interval

level

90%

sides

2-sided

lower limit

-11.6

upper limit

0.2

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 57 to Day 84

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	147	146	155	153
Units: percent
least squares mean (standard error)	19.8 ( 4.12 )	19.2 ( 4.03 )	12.3 ( 3.98 )	18.7 ( 3.99 )

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.779

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.1

Confidence interval

level

90%

sides

2-sided

lower limit

-5.4

upper limit

7.6

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

299

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.896

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.5

Confidence interval

level

90%

sides

2-sided

lower limit

-6

upper limit

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.099

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-6.4

Confidence interval

level

90%

sides

2-sided

lower limit

-12.8

upper limit

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 85 to End of 6 Months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	147	145	152	150
Units: percent
least squares mean (standard error)	21.2 ( 4.25 )	23.1 ( 4.16 )	15.8 ( 4.16 )	20 ( 4.14 )

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

297

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.767

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.2

Confidence interval

level

90%

sides

2-sided

lower limit

-5.5

upper limit

7.8

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

295

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.445

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.1

Confidence interval

level

90%

sides

2-sided

lower limit

-3.6

upper limit

9.8

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

302

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.298

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-4.2

Confidence interval

level

90%

sides

2-sided

lower limit

-10.8

upper limit

2.4

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Treatment Period

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	160	159
Units: percent
least squares mean (standard error)	16.6 ( 3.58 )	18.1 ( 3.51 )	11.5 ( 3.46 )	16.7 ( 3.46 )

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.969

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

90%

sides

2-sided

lower limit

-5.8

upper limit

5.5

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.3

Confidence interval

level

90%

sides

2-sided

lower limit

-4.3

upper limit

Percentage of rescue medication free days

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.124

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-5.2

Confidence interval

level

90%

sides

2-sided

lower limit

-10.9

upper limit

0.4

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

End point description

Treatment Period is defined as the percentage of night-time awakenings due to asthma symptoms across the entire 6-month double-blind treatment period for a patient (out of the total number of days where data was available within the treatment period, regardless of whether or not a patient was actually taking IP on that day).

End point type

Secondary

End point timeframe

Baseline and Day 1 to Day 28

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	156	153	161	159
Units: percent
least squares mean (standard error)	-11.3 ( 2.85 )	-11.1 ( 2.8 )	-10.1 ( 2.75 )	-8.9 ( 2.76 )

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

315

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.375

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.4

Confidence interval

level

90%

sides

2-sided

lower limit

-6.9

upper limit

2.1

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.424

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.2

Confidence interval

level

90%

sides

2-sided

lower limit

-6.7

upper limit

2.3

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.663

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.2

Confidence interval

level

90%

sides

2-sided

lower limit

-5.6

upper limit

3.3

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 29 to Day 56

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	152	148	158	156
Units: percent
least squares mean (standard error)	-18.2 ( 3.41 )	-19 ( 3.35 )	-15.2 ( 3.31 )	-15.2 ( 3.32 )

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.359

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3

Confidence interval

level

90%

sides

2-sided

lower limit

-8.3

upper limit

2.4

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

304

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.244

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.8

Confidence interval

level

90%

sides

2-sided

lower limit

-9.2

upper limit

1.6

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

314

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.995

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

90%

sides

2-sided

lower limit

-5.3

upper limit

5.3

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 57 to Day 84

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	149	146	155	154
Units: percent
least squares mean (standard error)	-22.1 ( 3.55 )	-19.8 ( 3.48 )	-17.6 ( 3.44 )	-16.7 ( 3.45 )

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derivedbaseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

303

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.111

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-5.4

Confidence interval

level

90%

sides

2-sided

lower limit

-10.9

upper limit

0.2

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.365

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.1

Confidence interval

level

90%

sides

2-sided

lower limit

-8.7

upper limit

2.5

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.793

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

90%

sides

2-sided

lower limit

-6.4

upper limit

4.6

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Top of page

End point title

Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

End point description

End point type

Secondary

End point timeframe

Baseline and Day 85 to End of 6 Months

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	148	145	153	152
Units: percent
least squares mean (standard error)	-25.3 ( 3.64 )	-25.5 ( 3.56 )	-22.8 ( 3.09 )	-21.8 ( 3.54 )

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 5mg v Placebo

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.318

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.4

Confidence interval

level

90%

sides

2-sided

lower limit

-9.1

upper limit

2.2

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD 5069 15 mg v Placebo

Number of subjects included in analysis

297

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.297

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.6

Confidence interval

level

90%

sides

2-sided

lower limit

-9.3

upper limit

2.1

Percentage of night-time awakenings

Statistical analysis description

Statistical analysis is based on an ANCOVA model with treatment, OCS use at baseline (yes or no) and derived baseline value included in the model.

Comparison groups

AZD5069 45mg v Placebo

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.776

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1

Confidence interval

level

90%

sides

2-sided

lower limit

-6.6

upper limit

4.6

Secondary: Uncontrolled asthma weeks based on eDiary

Top of page

End point title

Uncontrolled asthma weeks based on eDiary

End point description

An uncontrolled asthma week is defined as the fulfilment of 1 of the following conditions: 1) two consecutive days with awakenings due to asthma on both nights and 2) a recorded use of rescue medication for symptom relief on at least 3 occasions per day, for 2 consecutive days (where one occasion is defined as one puff of rescue medication).Baseline is defined as the last 2 weeks (14 days) before randomisation for each patient.

End point type

Secondary

End point timeframe

Baseline and 6 months treatment period

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	153	151	157	157
Units: weeks
arithmetic mean (standard deviation)	10.4 ( 9.84 )	10.7 ( 10.02 )	11 ( 10 )	10.9 ( 9.89 )

No statistical analyses for this end point

Secondary: Well-controlled asthma weeks based on eDiary

Top of page

End point title

Well-controlled asthma weeks based on eDiary

End point description

A well-controlled asthma week is defined as the fulfilment of both conditions: 1) no night-time awakenings due to asthma symptoms and no severe or mild/moderate asthma exacerbations and 2) two or more of the following 3 criteria are fulfilled: a) asthma symptoms on no more than 2 days with a daytime symptom score of >1, b) no more than 2 days of rescue medication use, up to a maximum of 4 occasions per week (where one occasion is defined as one puff of rescue medication) and c) >=80% of predicted normal(PN) morning PEF every day (according to the ERS guidelines).

End point type

Secondary

End point timeframe

Baseline and 6 months treatment period

End point values	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Number of subjects analysed	154	151	157	158
Units: weeks
arithmetic mean (standard deviation)	2.4 ( 5.38 )	1.9 ( 4.78 )	1.7 ( 4.38 )	2.3 ( 5.27 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Safety evaluations were performed for the 12 months of the study. 6-month results would be reported.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

AZD 5069 5mg

Reporting group description

Reporting group title

AZD 5069 15 mg

Reporting group description

Reporting group title

AZD5069 45mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Serious adverse events	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 156 (4.49%)	8 / 153 (5.23%)	14 / 161 (8.70%)	13 / 159 (8.18%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RENAL CANCER
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	1 / 159 (0.63%)
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
LUNG NEOPLASM MALIGNANT
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
UTERINE LEIOMYOMA
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
PERIPHERAL EMBOLISM
subjects affected / exposed	1 / 156 (0.64%)	0 / 153 (0.00%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
HYPERTENSION
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
OVARIAN CYST
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
ASTHMA
subjects affected / exposed	4 / 156 (2.56%)	3 / 153 (1.96%)	4 / 161 (2.48%)	3 / 159 (1.89%)
occurrences causally related to treatment / all	1 / 4	0 / 4	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ASTHMATIC CRISIS
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
PATELLA FRACTURE
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
PSEUDOHYPOPARATHYROIDISM
subjects affected / exposed	1 / 156 (0.64%)	0 / 153 (0.00%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	1 / 159 (0.63%)
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
CORONARY ARTERY DISEASE
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
CRITICAL ILLNESS POLYNEUROPATHY
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ISCHAEMIC STROKE
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
NEUTROPENIA
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
BARRETTS OESOPHAGUS
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
GASTRITIS
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
HIATUS HERNIA
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ABDOMINAL HERNIA
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
INGUINAL HERNIA
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
CHOLECYSTITIS CHRONIC
subjects affected / exposed	1 / 156 (0.64%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CHOLELITHIASIS
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
CALCULUS URETERIC
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
PNEUMONIA
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	3 / 161 (1.86%)	2 / 159 (1.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ABDOMINAL ABSCESS
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
HELICOBACTER GASTRITIS
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION BACTERIAL
subjects affected / exposed	1 / 156 (0.64%)	0 / 153 (0.00%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
SALMONELLOSIS
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
STREPTOCOCCAL SEPSIS
subjects affected / exposed	0 / 156 (0.00%)	1 / 153 (0.65%)	0 / 161 (0.00%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
VIRAL UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	1 / 161 (0.62%)	0 / 159 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ACUTE TONSILLITIS
subjects affected / exposed	0 / 156 (0.00%)	0 / 153 (0.00%)	0 / 161 (0.00%)	1 / 159 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	AZD 5069 5mg	AZD 5069 15 mg	AZD5069 45mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	67 / 156 (42.95%)	60 / 153 (39.22%)	72 / 161 (44.72%)	83 / 159 (52.20%)
Nervous system disorders
HEADACHE
subjects affected / exposed	6 / 156 (3.85%)	12 / 153 (7.84%)	12 / 161 (7.45%)	15 / 159 (9.43%)
occurrences all number	6	12	12	15
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
subjects affected / exposed	4 / 156 (2.56%)	4 / 153 (2.61%)	2 / 161 (1.24%)	1 / 159 (0.63%)
occurrences all number	4	4	2	1
NAUSEA
subjects affected / exposed	2 / 156 (1.28%)	3 / 153 (1.96%)	3 / 161 (1.86%)	3 / 159 (1.89%)
occurrences all number	2	3	3	3
DIARRHOEA
subjects affected / exposed	2 / 156 (1.28%)	0 / 153 (0.00%)	4 / 161 (2.48%)	2 / 159 (1.26%)
occurrences all number	2	0	4	2
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	1 / 156 (0.64%)	0 / 153 (0.00%)	4 / 161 (2.48%)	1 / 159 (0.63%)
occurrences all number	1	0	4	1
Respiratory, thoracic and mediastinal disorders
ASTHMA
subjects affected / exposed	4 / 156 (2.56%)	3 / 153 (1.96%)	4 / 161 (2.48%)	3 / 159 (1.89%)
occurrences all number	4	3	4	3
COUGH
subjects affected / exposed	3 / 156 (1.92%)	2 / 153 (1.31%)	1 / 161 (0.62%)	0 / 159 (0.00%)
occurrences all number	3	2	1	0
Musculoskeletal and connective tissue disorders
BACK PAIN
subjects affected / exposed	1 / 156 (0.64%)	4 / 153 (2.61%)	2 / 161 (1.24%)	6 / 159 (3.77%)
occurrences all number	1	4	2	6
ARTHRALGIA
subjects affected / exposed	2 / 156 (1.28%)	2 / 153 (1.31%)	1 / 161 (0.62%)	2 / 159 (1.26%)
occurrences all number	2	2	1	2
Infections and infestations
NASOPHARYNGITIS
subjects affected / exposed	18 / 156 (11.54%)	13 / 153 (8.50%)	18 / 161 (11.18%)	31 / 159 (19.50%)
occurrences all number	18	13	18	31
BRONCHITIS
subjects affected / exposed	1 / 156 (0.64%)	6 / 153 (3.92%)	7 / 161 (4.35%)	10 / 159 (6.29%)
occurrences all number	1	6	7	10
PHARYNGITIS
subjects affected / exposed	5 / 156 (3.21%)	4 / 153 (2.61%)	3 / 161 (1.86%)	5 / 159 (3.14%)
occurrences all number	5	4	3	5
VIRAL UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	3 / 156 (1.92%)	3 / 153 (1.96%)	6 / 161 (3.73%)	2 / 159 (1.26%)
occurrences all number	3	3	6	2
INFLUENZA
subjects affected / exposed	4 / 156 (2.56%)	3 / 153 (1.96%)	3 / 161 (1.86%)	3 / 159 (1.89%)
occurrences all number	4	3	3	3
PNEUMONIA
subjects affected / exposed	1 / 156 (0.64%)	2 / 153 (1.31%)	4 / 161 (2.48%)	3 / 159 (1.89%)
occurrences all number	1	2	4	3
RHINITIS
subjects affected / exposed	1 / 156 (0.64%)	4 / 153 (2.61%)	2 / 161 (1.24%)	0 / 159 (0.00%)
occurrences all number	1	4	2	0
SINUSITIS
subjects affected / exposed	3 / 156 (1.92%)	1 / 153 (0.65%)	3 / 161 (1.86%)	5 / 159 (3.14%)
occurrences all number	3	1	3	5
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 156 (0.64%)	1 / 153 (0.65%)	4 / 161 (2.48%)	3 / 159 (1.89%)
occurrences all number	1	1	4	3
URINARY TRACT INFECTION
subjects affected / exposed	0 / 156 (0.00%)	3 / 153 (1.96%)	3 / 161 (1.86%)	2 / 159 (1.26%)
occurrences all number	0	3	3	2
GASTROENTERITIS
subjects affected / exposed	1 / 156 (0.64%)	2 / 153 (1.31%)	1 / 161 (0.62%)	2 / 159 (1.26%)
occurrences all number	1	2	1	2
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	6 / 156 (3.85%)	2 / 153 (1.31%)	3 / 161 (1.86%)	3 / 159 (1.89%)
occurrences all number	6	2	3	3

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Were there any global substantial amendments to the protocol? Yes

10 Oct 2012

Clarification regarding the use of contraception during the study after new in vitro results became available. Clarification that patients were to contact the investigator regarding increased body temperatures and for worsening of asthma signs.

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: number of severe exacerbations over 6 months

Primary: number of severe exacerbations over 6 months

Primary: total number of days of severe exacerbation

Primary: total number of days of severe exacerbation

Primary: Patients experiencing one or more severe exacerbations

Primary: Patients experiencing one or more severe exacerbations

Secondary: event of asthma-specific hospital/intensive care unit (ICU)admissions

Secondary: event of asthma-specific hospital/intensive care unit (ICU)admissions

Secondary: total number of days of asthma-specific hospital /intensive care unit (ICU) admissions

Secondary: total number of days of asthma-specific hospital /intensive care unit (ICU) admissions

Secondary: total number of days of oral corticosteroids (OCS) use due to worsening in asthma symptoms

Secondary: total number of days of oral corticosteroids (OCS) use due to worsening in asthma symptoms

Secondary: Pre-bronchodilator FEV1,measured before the morning administration of the investigational product

Secondary: Pre-bronchodilator FEV1,measured before the morning administration of the investigational product

Secondary: Post-bronchodilator FEV1,measured before the morning administration of the investigational product

Secondary: Post-bronchodilator FEV1,measured before the morning administration of the investigational product

Secondary: Asthma control questionnaire [ACQ-5] score change from baseline to treatment period

Secondary: Asthma control questionnaire [ACQ-5] score change from baseline to treatment period

Secondary: Asthma quality of life questionnaire (AQLQ[s]) overall and domain scores change from baseline to treatment period

Secondary: Asthma quality of life questionnaire (AQLQ[s]) overall and domain scores change from baseline to treatment period

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of symptom-free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of asthma-control days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of rescue medication free days (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Percentage of night-time awakenings due to asthma symptoms (eDiary) change from baseline to post-randomisation periods

Secondary: Uncontrolled asthma weeks based on eDiary

Secondary: Uncontrolled asthma weeks based on eDiary

Secondary: Well-controlled asthma weeks based on eDiary

Secondary: Well-controlled asthma weeks based on eDiary

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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