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Clinical Trial Results:
A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Parallel Arm, Multi-Centre Study to Assess Efficacy and Safety of Multiple Dose Levels of AZD7594 DPI Given Once Daily for Twelve Weeks, Compared to Placebo, in Asthmatics Symptomatic on Low Dose ICS

Summary
EudraCT number	2017-002483-40
Trial protocol	DE HU BG PL
Global end of trial date	30 Sep 2019

Results information
Results version number	v1(current)
This version publication date	20 Sep 2020
First version publication date	20 Sep 2020
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

D3741C00007

ISRCTN number

US NCT number

NCT03622112

WHO universal trial number (UTN)

Sponsor organisation name

AstraZeneca AB

Sponsor organisation address

Södertälje, Södertälje, Sweden, 151 85

Public contact

Global Clinical Lead, AstraZeneca AB, 301 3985799, ClinicalTrialTransparency@astrazeneca.com

Scientific contact

Global Clinical Lead, AstraZeneca AB, 301 3985799, ClinicalTrialTransparency@astrazeneca.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

21 Nov 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Sep 2019

Was the trial ended prematurely?

Main objective of the trial

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose Inhaled Corticosteroid (ICS)

Protection of trial subjects

The global study protocol, the country-specific protocols and all protocol amendments, including all versions of informed consent forms (ICFs) and any other written information and/or materials provided to the subjects were approved by an Independent Ethics Committee/Institutional Review Board (IEC/ IRB) in writing. This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice (ICH/ GCP), applicable regulatory requirements and the AstraZeneca policy on Bioethics.The applicable regulatory requirements in Japan were GCP for Trials on Drugs ((Ministry of Health, Labour and Welfare [MHLW] Ordinance No.28, 27 March 1997, partially revised by MHLW Ordinance and their related notifications). Before signing the ICF, each subject was given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study. Every subject was given the opportunity to ask questions and allowed time to consider the information provided and was notified that he/she was free to discontinue from the study at any time.

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Jan 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 135

Country: Number of subjects enrolled

Japan: 82

Country: Number of subjects enrolled

Poland: 142

Country: Number of subjects enrolled

Ukraine: 125

Country: Number of subjects enrolled

Germany: 120

Country: Number of subjects enrolled

Hungary: 99

Country: Number of subjects enrolled

Bulgaria: 85

Country: Number of subjects enrolled

South Africa: 18

Worldwide total number of subjects

806

EEA total number of subjects

446

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)

630

From 65 to 84 years

176

85 years and over

Subject disposition

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Recruitment details

The study was conducted in 92 sites in 8 countries; Bulgaria, Germany, Hungary, Poland, and Ukraine, United States (US), South Africa, and Japan. In this study, 806 subjects (including 82 Japanese subjects) were randomised. For sites in the US, no subjects were randomised to the AZD7594 792 μg/720 μg once daily (QD) treatment arm.

Screening details

Subjects attended a Screening Visit within 28 days before receiving their first dose. All subjects underwent inclusion exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

AZD7594 50 μg

Arm description

Oral inhalation of AZD5794 55 μg/ 50 μg (nominal dose/delivered dose) once daily (QD).

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Oral use

Dosage and administration details

55 μg/50 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, dry powder inhaler (DPI)) QD

AZD7594 90 μg

Arm description

Oral inhalation of AZD5794 99 μg/ 90 μg (nominal dose/delivered dose) once daily.

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Oral use

Dosage and administration details

99 μg/90 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD

AZD7594 180 μg

Arm description

Oral inhalation of AZD5794 198 μg/ 180 μg (nominal dose/delivered dose) once daily.

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Oral use

Dosage and administration details

198 μg/180 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD

AZD7594 360 μg

Arm description

Oral inhalation of AZD5794 396 μg/ 360 μg (nominal dose/delivered dose) once daily.

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Oral use

Dosage and administration details

396 μg/360 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD

AZD7594 720 μg

Arm description

Oral inhalation of AZD5794 792 μg/ 720 μg (nominal dose/delivered dose) once daily.

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Oral use

Dosage and administration details

792 μg/720 μg (nominal dose/delivered dose), Oral inhalation (by SD3FL inhaler, DPI) QD (US excluded)

Placebo to AZD7594

Arm description

Oral inhalation of placebo to AZD7594 once daily.

Arm type

Placebo

Investigational medicinal product name

Placebo to AZD7594

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Oral use

Dosage and administration details

Matching Placebo to AZD7594, Oral inhalation (by SD3FL inhaler, DPI) QD

Fluticasone furoate

Arm description

Oral inhalation of fluticasone furoate 100 μg once daily.

Arm type

Experimental

Investigational medicinal product name

Fluticasone furoate

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Oral use

Dosage and administration details

100 μg per nominal dose, Oral inhalation (by ELLIPTA inhaler, DPI) QD

Number of subjects in period 1 ^[1]	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Started	110	112	111	113	134	113	112
Completed	85	92	95	91	124	71	103
Not completed	25	20	16	22	10	42	9
Adverse event, serious fatal	-	-	-	1	-	-	-
Consent withdrawn by subject	6	2	4	2	1	2	2
Adverse event, non-fatal	6	8	4	11	4	20	2
Study-specific withdrawal criteria	10	8	7	6	4	18	4
Lost to follow-up	1	1	-	-	-	-	-
Reason not specified	-	1	-	1	1	2	1
Protocol deviation	2	-	1	1	-	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: One randomized subject did not receive treatment as the subject deviated from the protocol and was randomized in error.

Baseline characteristics

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Reporting group title

AZD7594 50 μg

Reporting group description

Oral inhalation of AZD5794 55 μg/ 50 μg (nominal dose/delivered dose) once daily (QD).

Reporting group title

AZD7594 90 μg

Reporting group description

Oral inhalation of AZD5794 99 μg/ 90 μg (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 180 μg

Reporting group description

Oral inhalation of AZD5794 198 μg/ 180 μg (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 360 μg

Reporting group description

Oral inhalation of AZD5794 396 μg/ 360 μg (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 720 μg

Reporting group description

Oral inhalation of AZD5794 792 μg/ 720 μg (nominal dose/delivered dose) once daily.

Reporting group title

Placebo to AZD7594

Reporting group description

Oral inhalation of placebo to AZD7594 once daily.

Reporting group title

Fluticasone furoate

Reporting group description

Oral inhalation of fluticasone furoate 100 μg once daily.

Reporting group values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate	Total
Number of subjects	110	112	111	113	134	113	112	805
Age Categorical
Units: Subjects
<=18 years	0	0	0	0	0	0	0	0
Between 18 and 65 years	90	92	79	92	107	87	82	629
>=65 years	20	20	32	21	27	26	30	176
Age Continuous
Units: Years
arithmetic mean (standard deviation)	52.2 ( 12.8 )	53.2 ( 13.3 )	54.6 ( 14.5 )	52.8 ( 13.2 )	52.2 ( 13.0 )	53.4 ( 13.7 )	53.7 ( 13.4 )	-
Sex: Female, Male
Units: Subjects
Female	59	66	72	64	79	68	59	467
Male	51	46	39	49	55	45	53	338
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	1	0	0	0	0	0	1
Asian	9	11	10	13	16	13	12	84
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Black or African American	5	5	5	2	1	5	7	30
White	95	93	94	97	115	92	93	679
More than one race	1	2	2	1	2	3	0	11
Unknown or Not Reported	0	0	0	0	0	0	0	0

End points

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Reporting group title

AZD7594 50 μg

Reporting group description

Oral inhalation of AZD5794 55 μg/ 50 μg (nominal dose/delivered dose) once daily (QD).

Reporting group title

AZD7594 90 μg

Reporting group description

Oral inhalation of AZD5794 99 μg/ 90 μg (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 180 μg

Reporting group description

Oral inhalation of AZD5794 198 μg/ 180 μg (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 360 μg

Reporting group description

Oral inhalation of AZD5794 396 μg/ 360 μg (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 720 μg

Reporting group description

Oral inhalation of AZD5794 792 μg/ 720 μg (nominal dose/delivered dose) once daily.

Reporting group title

Placebo to AZD7594

Reporting group description

Oral inhalation of placebo to AZD7594 once daily.

Reporting group title

Fluticasone furoate

Reporting group description

Oral inhalation of fluticasone furoate 100 μg once daily.

Primary: Change from baseline in trough Forced expiratory volume in 1 second (FEV1) at Week 12

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End point title

Change from baseline in trough Forced expiratory volume in 1 second (FEV1) at Week 12

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first investigational product (IP) administration (30 minutes apart, at −45 minutes and −15 minutes, before IP administration) on Day 1 (Visit 3). Analyses were based on a Mixed-effects model for repeated measures (MMRM) with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates.

End point type

Primary

End point timeframe

At Baseline and Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	83	90	92	90	123	70	103
Units: Liters
least squares mean (confidence interval 95%)	-0.013 (-0.077 to 0.050)	-0.031 (-0.094 to 0.031)	0.062 (-0.001 to 0.124)	0.099 (0.036 to 0.161)	0.104 (0.046 to 0.162)	0.022 (-0.046 to 0.091)	0.133 (0.073 to 0.193)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.437

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.036

Confidence interval

level

95%

sides

2-sided

lower limit

-0.126

upper limit

0.054

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.236

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.054

Confidence interval

level

95%

sides

2-sided

lower limit

-0.143

upper limit

0.035

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.389

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.039

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.128

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.094

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.076

Confidence interval

level

95%

sides

2-sided

lower limit

-0.013

upper limit

0.165

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

193

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.082

Confidence interval

level

95%

sides

2-sided

lower limit

-0.003

upper limit

0.167

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.014

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.111

Confidence interval

level

95%

sides

2-sided

lower limit

0.023

upper limit

0.199

Notes
[1] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in trough FEV1 at Weeks 2, 4, 8 and average over the Treatment Period

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End point title

Change from baseline in trough FEV1 at Weeks 2, 4, 8 and average over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period. Baseline was defined as the mean of the 2 measured values before first IP administration on Day 1. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. Analysis of covariance (ANCOVA) with treatment and region (ie, US, Japan, and Rest of the World [RoW]) as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. The reported number of subjects analysed corresponds to Week 2 and for Weeks 4, 8, 12 and average over the Treatment Period, the number of subjects analysed are provided as comment in the row titles.

End point type

Secondary

End point timeframe

At Baseline and Weeks 2, 4 and 8

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	108	107	108	104	132	95	109
Units: Liters
least squares mean (confidence interval 95%)
Week 2	0.018 (-0.038 to 0.073)	0.011 (-0.044 to 0.066)	0.067 (0.011 to 0.122)	0.091 (0.036 to 0.147)	0.093 (0.041 to 0.146)	-0.011 (-0.070 to 0.048)	0.107 (0.052 to 0.161)
Week 4 (n=98, 103, 103, 104, 127, 84, 110)	-0.002 (-0.063 to 0.059)	0.039 (-0.021 to 0.099)	0.078 (0.018 to 0.138)	0.086 (0.027 to 0.146)	0.094 (0.037 to 0.151)	-0.020 (-0.085 to 0.045)	0.145 (0.086 to 0.204)
Week 8 (n=90, 96, 100, 96, 125, 76, 105)	0.019 (-0.044 to 0.082)	0.007 (-0.055 to 0.069)	0.071 (0.010 to 0.133)	0.102 (0.040 to 0.163)	0.141 (0.083 to 0.199)	0.002 (-0.066 to 0.069)	0.124 (0.064 to 0.184)
Treatment Period Avg(n=108,109,108,109,132,95,110)	0.005 (-0.049 to 0.059)	0.006 (-0.047 to 0.059)	0.069 (0.016 to 0.123)	0.094 (0.041 to 0.148)	0.108 (0.057 to 0.159)	-0.002 (-0.059 to 0.056)	0.127 (0.075 to 0.180)

Statistical Analysis at Week 2

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.463

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.029

Confidence interval

level

95%

sides

2-sided

lower limit

-0.048

upper limit

0.105

Statistical Analysis at Week 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.576

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.022

Confidence interval

level

95%

sides

2-sided

lower limit

-0.055

upper limit

0.098

Statistical Analysis at Week 2

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.047

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.078

Confidence interval

level

95%

sides

2-sided

lower limit

0.001

upper limit

0.154

Statistical Analysis at Week 2

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.102

Confidence interval

level

95%

sides

2-sided

lower limit

0.025

upper limit

0.179

Statistical Analysis at Week 2

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

227

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.104

Confidence interval

level

95%

sides

2-sided

lower limit

0.031

upper limit

0.178

Statistical Analysis at Week 2

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

204

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.003

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.118

Confidence interval

level

95%

sides

2-sided

lower limit

0.041

upper limit

0.194

Notes
[2] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis at Week 4

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.685

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.018

Confidence interval

level

95%

sides

2-sided

lower limit

-0.068

upper limit

0.103

Statistical Analysis at Week 4

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.176

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.059

Confidence interval

level

95%

sides

2-sided

lower limit

-0.026

upper limit

0.144

Statistical Analysis at Week 4

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.024

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.098

Confidence interval

level

95%

sides

2-sided

lower limit

0.013

upper limit

0.183

Statistical Analysis at Week 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.106

Confidence interval

level

95%

sides

2-sided

lower limit

0.021

upper limit

0.191

Statistical Analysis at Week 4

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

227

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.114

Confidence interval

level

95%

sides

2-sided

lower limit

0.032

upper limit

0.196

Statistical Analysis at Week 4

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

204

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.165

Confidence interval

level

95%

sides

2-sided

lower limit

0.081

upper limit

0.249

Notes
[3] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis at Week 8

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.707

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.017

Confidence interval

level

95%

sides

2-sided

lower limit

-0.072

upper limit

0.106

Statistical Analysis at Week 8

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.904

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.005

Confidence interval

level

95%

sides

2-sided

lower limit

-0.083

upper limit

0.094

Statistical Analysis at Week 8

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.121

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.018

upper limit

0.157

Statistical Analysis at Week 8

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.012

upper limit

0.188

Statistical Analysis at Week 8

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

227

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.139

Confidence interval

level

95%

sides

2-sided

lower limit

0.055

upper limit

0.224

Statistical Analysis at Week 8

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

204

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.122

Confidence interval

level

95%

sides

2-sided

lower limit

0.035

upper limit

0.209

Notes
[4] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.856

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.007

Confidence interval

level

95%

sides

2-sided

lower limit

-0.068

upper limit

0.081

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.832

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.008

Confidence interval

level

95%

sides

2-sided

lower limit

-0.066

upper limit

0.082

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.071

Confidence interval

level

95%

sides

2-sided

lower limit

-0.003

upper limit

0.145

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.096

Confidence interval

level

95%

sides

2-sided

lower limit

0.022

upper limit

0.17

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

227

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.039

upper limit

0.181

Statistical Analysis for Treatment period average

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

204

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.129

Confidence interval

level

95%

sides

2-sided

lower limit

0.055

upper limit

0.202

Notes
[5] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in Fractional exhaled nitic oxide (FENO) at Weeks 2, 4, 8, 12 and average over the Treatment Period

Top of page

End point title

Change from baseline in Fractional exhaled nitic oxide (FENO) at Weeks 2, 4, 8, 12 and average over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the last value obtained prior to the first dose of investigational product. Analyses were based on a MMRM with change from baseline on the log-scale as the response, treatment, visit, treatment by visit interaction and region as fixed effects, and log-transformed baseline value and baseline by visit interaction as covariates. The reported number of subjects analysed corresponds to Week 2 and for Weeks 4, 8, 12 and average over the Treatment Period, the number of subjects analysed are provided as comment in the row titles.

End point type

Secondary

End point timeframe

At Baseline and Weeks 2, 4, 8, and 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	107	105	107	102	127	95	104
Units: ppb
geometric mean (confidence interval 95%)
Week 2	1.307 (1.190 to 1.436)	1.223 (1.113 to 1.343)	1.175 (1.070 to 1.290)	1.152 (1.048 to 1.267)	0.959 (0.876 to 1.049)	1.396 (1.263 to 1.542)	0.880 (0.801 to 0.967)
Week 4 (n=95,100,103,102,126,84,105)	1.229 (1.109 to 1.363)	1.203 (1.087 to 1.332)	1.220 (1.103 to 1.349)	1.118 (1.011 to 1.237)	0.980 (0.891 to 1.078)	1.321 (1.184 to 1.475)	0.928 (0.840 to 1.025)
Week 8 (n=87,90,97,93,122,76,101)	1.294 (1.157 to 1.447)	1.316 (1.179 to 1.470)	1.250 (1.122 to 1.392)	1.206 (1.082 to 1.345)	1.021 (0.923 to 1.129)	1.411 (1.252 to 1.591)	0.906 (0.815 to 1.007)
Week 12 (n=79,89,89,88,121,70,100)	1.367 (1.219 to 1.532)	1.405 (1.258 to 1.569)	1.281 (1.148 to 1.431)	1.198 (1.072 to 1.337)	0.958 (0.866 to 1.060)	1.474 (1.305 to 1.664)	0.918 (0.826 to 1.022)
Treatment Period Avg(n=109,107,108,109,132,95,110)	1.298 (1.188 to 1.419)	1.284 (1.176 to 1.402)	1.231 (1.128 to 1.343)	1.168 (1.070 to 1.275)	0.979 (0.901 to 1.064)	1.399 (1.273 to 1.538)	0.908 (0.833 to 0.989)

Statistical Analysis at Week 2

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.322

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.936

Confidence interval

level

95%

sides

2-sided

lower limit

0.822

upper limit

1.067

Statistical Analysis at Week 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.047

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.876

Confidence interval

level

95%

sides

2-sided

lower limit

0.768

upper limit

0.999

Statistical Analysis at Week 2

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.842

Confidence interval

level

95%

sides

2-sided

lower limit

0.739

upper limit

0.959

Statistical Analysis at Week 2

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.825

Confidence interval

level

95%

sides

2-sided

lower limit

0.724

upper limit

0.941

Statistical Analysis at Week 2

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.687

Confidence interval

level

95%

sides

2-sided

lower limit

0.606

upper limit

0.779

Statistical Analysis at Week 2

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.553

upper limit

0.719

Notes
[6] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis at Week 4

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.329

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.931

Confidence interval

level

95%

sides

2-sided

lower limit

0.805

upper limit

1.076

Statistical Analysis at Week 4

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.203

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.911

Confidence interval

level

95%

sides

2-sided

lower limit

0.789

upper limit

1.052

Statistical Analysis at Week 4

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.273

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.923

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.065

Statistical Analysis at Week 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.023

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.846

Confidence interval

level

95%

sides

2-sided

lower limit

0.734

upper limit

0.977

Statistical Analysis at Week 4

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.742

Confidence interval

level

95%

sides

2-sided

lower limit

0.646

upper limit

0.852

Statistical Analysis at Week 4

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.703

Confidence interval

level

95%

sides

2-sided

lower limit

0.609

upper limit

0.81

Notes
[7] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis at Week 8

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.283

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.917

Confidence interval

level

95%

sides

2-sided

lower limit

0.783

upper limit

1.074

Statistical Analysis at Week 8

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.386

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.933

Confidence interval

level

95%

sides

2-sided

lower limit

0.797

upper limit

1.092

Statistical Analysis at Week 8

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.126

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.886

Confidence interval

level

95%

sides

2-sided

lower limit

0.758

upper limit

1.035

Statistical Analysis at Week 8

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.855

Confidence interval

level

95%

sides

2-sided

lower limit

0.731

upper limit

Statistical Analysis at Week 8

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.723

Confidence interval

level

95%

sides

2-sided

lower limit

0.623

upper limit

0.84

Statistical Analysis at Week 8

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.642

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

0.749

Notes
[8] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis at Week 12

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.359

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.927

Confidence interval

level

95%

sides

2-sided

lower limit

0.789

upper limit

1.09

Statistical Analysis at Week 12

Comparison groups

Placebo to AZD7594 v AZD7594 90 μg

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.556

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.953

Confidence interval

level

95%

sides

2-sided

lower limit

0.813

upper limit

1.118

Statistical Analysis at Week 12

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.084

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.869

Confidence interval

level

95%

sides

2-sided

lower limit

0.742

upper limit

1.019

Statistical Analysis at Week 12

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.813

Confidence interval

level

95%

sides

2-sided

lower limit

0.693

upper limit

0.953

Statistical Analysis at Week 12

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.559

upper limit

0.757

Statistical Analysis at Week 12

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.623

Confidence interval

level

95%

sides

2-sided

lower limit

0.533

upper limit

0.729

Notes
[9] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.231

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.928

Confidence interval

level

95%

sides

2-sided

lower limit

0.821

upper limit

1.049

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.17

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.918

Confidence interval

level

95%

sides

2-sided

lower limit

0.812

upper limit

1.037

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.039

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.879

Confidence interval

level

95%

sides

2-sided

lower limit

0.778

upper limit

0.994

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.835

Confidence interval

level

95%

sides

2-sided

lower limit

0.739

upper limit

0.943

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.622

upper limit

0.787

Statistical Analysis for Treatment period average

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.649

Confidence interval

level

95%

sides

2-sided

lower limit

0.575

upper limit

0.732

Notes
[10] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in trough Forced vital capacity (FVC) at Week 12 and average over the Treatment Period

Top of page

End point title

Change from baseline in trough Forced vital capacity (FVC) at Week 12 and average over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS(Full Analysis Set).Trough value was defined as the mean of the 2 measurements 30 minutes apart(23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Week 2 to Week 12).Baseline was defined as the mean of the 2 measured values before first IP administration(30 minutes apart, at −45 minutes and −15 minutes, before IP administration) on Day 1. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. Analysis of covariance with treatment and region as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. Reported number of subjects analysed corresponds to Week 12 and for average over the Treatment Period, the number of subjects analysed are provided as comment in row title.

End point type

Secondary

End point timeframe

At Baseline and Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	83	90	92	90	123	70	103
Units: Liters
least squares mean (confidence interval 95%)
Week 12	0.027 (-0.047 to 0.101)	-0.017 (-0.089 to 0.056)	0.076 (0.005 to 0.148)	0.119 (0.047 to 0.191)	0.088 (0.021 to 0.155)	0.061 (-0.018 to 0.141)	0.118 (0.048 to 0.188)
Treatment Period Avg(n=108,109,108,109,132,95,110)	0.044 (-0.017 to 0.106)	0.019 (-0.041 to 0.080)	0.087 (0.026 to 0.148)	0.127 (0.066 to 0.188)	0.091 (0.033 to 0.149)	0.046 (-0.020 to 0.112)	0.121 (0.062 to 0.181)

Statistical Analysis at Week 12

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.519

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.034

Confidence interval

level

95%

sides

2-sided

lower limit

-0.139

upper limit

0.07

Statistical Analysis at Week 12

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.141

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.078

Confidence interval

level

95%

sides

2-sided

lower limit

-0.181

upper limit

0.026

Statistical Analysis at Week 12

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.772

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.015

Confidence interval

level

95%

sides

2-sided

lower limit

-0.088

upper limit

0.119

Statistical Analysis at Week 12

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.27

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.058

Confidence interval

level

95%

sides

2-sided

lower limit

-0.045

upper limit

0.162

Statistical Analysis at Week 12

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

193

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.592

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.027

Confidence interval

level

95%

sides

2-sided

lower limit

-0.072

upper limit

0.126

Statistical Analysis at Week 12

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 0.275

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.057

Confidence interval

level

95%

sides

2-sided

lower limit

-0.045

upper limit

0.158

Notes
[11] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.963

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.002

Confidence interval

level

95%

sides

2-sided

lower limit

-0.087

upper limit

0.083

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.533

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.027

Confidence interval

level

95%

sides

2-sided

lower limit

-0.112

upper limit

0.058

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.342

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.041

Confidence interval

level

95%

sides

2-sided

lower limit

-0.044

upper limit

0.126

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.061

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.081

Confidence interval

level

95%

sides

2-sided

lower limit

-0.004

upper limit

0.165

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

193

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.278

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.045

Confidence interval

level

95%

sides

2-sided

lower limit

-0.037

upper limit

0.127

Statistical Analysis for Treatment period average

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.079

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.075

Confidence interval

level

95%

sides

2-sided

lower limit

-0.009

upper limit

0.159

Notes
[12] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and average over the Treatment Period

Top of page

End point title

Change from baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and average over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the ACQ-5 score at Visit 3. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. Analysis of covariance with treatment and region as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. The questionnaire has 5 items; each item is scored on a scale of 0 to 6, where higher scores represent more severe impairment/symptoms. The overall ACQ-5 score is the average of the scores for each of the questions included in the questionnaire. Reported number of subjects analysed corresponds to Week 12 and for average over the Treatment Period, the number of subjects analysed are provided as comment in row title.

End point type

Secondary

End point timeframe

At Baseline and Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	83	91	93	90	122	70	103
Units: units on a scale
least squares mean (confidence interval 95%)
Week 12	-0.289 (-0.412 to -0.166)	-0.394 (-0.513 to -0.274)	-0.357 (-0.476 to -0.239)	-0.330 (-0.449 to -0.210)	-0.406 (-0.514 to -0.297)	-0.137 (-0.269 to -0.004)	-0.360 (-0.474 to -0.245)
Treatment Period Avg(n=108,110,108,110,132,101,110	-0.215 (-0.307 to -0.122)	-0.230 (-0.322 to -0.139)	-0.220 (-0.311 to -0.128)	-0.291 (-0.382 to -0.199)	-0.306 (-0.394 to -0.219)	-0.090 (-0.187 to 0.008)	-0.269 (-0.359 to -0.179)

Statistical Analysis at Week 12

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.088

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.153

Confidence interval

level

95%

sides

2-sided

lower limit

-0.328

upper limit

0.023

Statistical Analysis at Week 12

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

161

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.257

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

-0.084

Statistical Analysis at Week 12

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.221

Confidence interval

level

95%

sides

2-sided

lower limit

-0.393

upper limit

-0.049

Statistical Analysis at Week 12

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.193

Confidence interval

level

95%

sides

2-sided

lower limit

-0.366

upper limit

-0.02

Statistical Analysis at Week 12

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.269

Confidence interval

level

95%

sides

2-sided

lower limit

-0.434

upper limit

-0.104

Statistical Analysis at Week 12

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.223

Confidence interval

level

95%

sides

2-sided

lower limit

-0.393

upper limit

-0.054

Notes
[13] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.055

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.125

Confidence interval

level

95%

sides

2-sided

lower limit

-0.253

upper limit

0.003

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

161

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.141

Confidence interval

level

95%

sides

2-sided

lower limit

-0.268

upper limit

-0.014

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

163

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.044

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.257

upper limit

-0.003

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.201

Confidence interval

level

95%

sides

2-sided

lower limit

-0.328

upper limit

-0.074

Statistical Analysis for Treatment period average

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.217

Confidence interval

level

95%

sides

2-sided

lower limit

-0.339

upper limit

-0.094

Statistical Analysis for Treatment period average

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

= 0.005

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.179

Confidence interval

level

95%

sides

2-sided

lower limit

-0.305

upper limit

-0.053

Notes
[14] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in average morning Peak Expiratory Flow (PEF) over the Treatment Period

Top of page

End point title

Change from baseline in average morning Peak Expiratory Flow (PEF) over the Treatment Period

End point description

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	89	94	97	92	122	73	104
Units: Liters/minute
least squares mean (confidence interval 95%)	-4.036 (-10.518 to 2.447)	-5.718 (-11.994 to 0.557)	-2.576 (-8.768 to 3.617)	3.745 (-2.558 to 10.048)	4.900 (-1.010 to 10.810)	-11.699 (-18.749 to -4.649)	-1.208 (-7.209 to 4.793)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.097

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.664

Confidence interval

level

95%

sides

2-sided

lower limit

-1.403

upper limit

16.73

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.19

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.981

Confidence interval

level

95%

sides

2-sided

lower limit

-2.98

upper limit

14.941

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.045

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

9.123

Confidence interval

level

95%

sides

2-sided

lower limit

0.195

upper limit

18.052

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

15.444

Confidence interval

level

95%

sides

2-sided

lower limit

6.443

upper limit

24.445

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

16.599

Confidence interval

level

95%

sides

2-sided

lower limit

8.031

upper limit

25.167

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

= 0.019

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.491

Confidence interval

level

95%

sides

2-sided

lower limit

1.726

upper limit

19.256

Notes
[15] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in average evening PEF over the Treatment Period

Top of page

End point title

Change from baseline in average evening PEF over the Treatment Period

End point description

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	88	93	96	92	119	73	102
Units: Liters/minute
least squares mean (confidence interval 95%)	-5.418 (-11.792 to 0.955)	-5.654 (-11.843 to 0.534)	-3.983 (-10.081 to 2.114)	2.441 (-3.738 to 8.620)	4.178 (-1.642 to 9.997)	-7.816 (-14.712 to -0.921)	-1.687 (-7.602 to 4.227)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

161

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.597

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.398

Confidence interval

level

95%

sides

2-sided

lower limit

-6.494

upper limit

11.29

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.629

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.162

Confidence interval

level

95%

sides

2-sided

lower limit

-6.623

upper limit

10.948

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.389

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.833

Confidence interval

level

95%

sides

2-sided

lower limit

-4.907

upper limit

12.573

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.258

Confidence interval

level

95%

sides

2-sided

lower limit

1.456

upper limit

19.059

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.994

Confidence interval

level

95%

sides

2-sided

lower limit

3.571

upper limit

20.417

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority ^[16]

P-value

= 0.163

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.129

Confidence interval

level

95%

sides

2-sided

lower limit

-2.479

upper limit

14.737

Notes
[16] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in average daily use of rescue medication over the Treatment Period

Top of page

End point title

Change from baseline in average daily use of rescue medication over the Treatment Period

End point description

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	86	86	91	79	109	66	93
Units: number of puffs
least squares mean (confidence interval 95%)	-0.370 (-0.502 to -0.237)	-0.282 (-0.415 to -0.149)	-0.226 (-0.356 to -0.096)	-0.435 (-0.572 to -0.297)	-0.435 (-0.560 to -0.310)	-0.127 (-0.276 to 0.023)	-0.304 (-0.432 to -0.175)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.243

Confidence interval

level

95%

sides

2-sided

lower limit

-0.431

upper limit

-0.054

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.108

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.155

Confidence interval

level

95%

sides

2-sided

lower limit

-0.344

upper limit

0.034

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.295

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.099

Confidence interval

level

95%

sides

2-sided

lower limit

-0.286

upper limit

0.087

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.308

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

-0.116

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.308

Confidence interval

level

95%

sides

2-sided

lower limit

-0.489

upper limit

-0.126

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

= 0.062

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.177

Confidence interval

level

95%

sides

2-sided

lower limit

-0.362

upper limit

0.009

Notes
[17] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in percent night-time awakening days over the Treatment Period

Top of page

End point title

Change from baseline in percent night-time awakening days over the Treatment Period

End point description

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	89	94	97	92	122	73	104
Units: percentage
least squares mean (confidence interval 95%)	-14.281 (-18.408 to -10.154)	-12.260 (-16.263 to -8.257)	-8.649 (-12.579 to -4.718)	-12.085 (-16.102 to -8.068)	-13.017 (-16.790 to -9.244)	-4.288 (-8.814 to 0.238)	-15.910 (-19.753 to -12.067)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-9.993

Confidence interval

level

95%

sides

2-sided

lower limit

-15.795

upper limit

-4.191

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-7.972

Confidence interval

level

95%

sides

2-sided

lower limit

-13.694

upper limit

-2.251

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

170

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.133

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-4.361

Confidence interval

level

95%

sides

2-sided

lower limit

-10.051

upper limit

1.329

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-7.797

Confidence interval

level

95%

sides

2-sided

lower limit

-13.555

upper limit

-2.04

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-8.729

Confidence interval

level

95%

sides

2-sided

lower limit

-14.195

upper limit

-3.264

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

superiority ^[18]

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-11.622

Confidence interval

level

95%

sides

2-sided

lower limit

-17.211

upper limit

-6.034

Notes
[18] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in average daily asthma symptom score over the Treatment Period

Top of page

End point title

Change from baseline in average daily asthma symptom score over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. During the Run-in and Treatment Periods, subjects recorded the severity of their asthma symptoms during night-time and day-time each morning and evening, using the eDiary. Asthma symptom scores during night-time/day-time were assessed by the subject each morning/evening according to the following scoring system and recorded on the eDiary: 0: No asthma symptoms, 1: The subjects were aware of their asthma symptoms but they can easily tolerate the symptoms, 2: asthma was causing enough discomfort to cause problems with sleep, 3: Subjects were unable to sleep/do normal activities because of their asthma.

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	86	86	91	79	109	66	93
Units: Unit on a scale
least squares mean (confidence interval 95%)	-0.303 (-0.385 to -0.220)	-0.201 (-0.283 to -0.118)	-0.229 (-0.310 to -0.149)	-0.321 (-0.407 to -0.235)	-0.275 (-0.353 to -0.198)	-0.091 (-0.184 to 0.003)	-0.296 (-0.376 to -0.216)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.212

Confidence interval

level

95%

sides

2-sided

lower limit

-0.329

upper limit

-0.094

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.228

upper limit

0.007

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.139

Confidence interval

level

95%

sides

2-sided

lower limit

-0.255

upper limit

-0.022

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

-0.11

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.185

Confidence interval

level

95%

sides

2-sided

lower limit

-0.298

upper limit

-0.071

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.206

Confidence interval

level

95%

sides

2-sided

lower limit

-0.321

upper limit

-0.09

Notes
[19] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in percent asthma control days over the Treatment Period

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End point title

Change from baseline in percent asthma control days over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Asthma-control days was defined as days with no symptoms, no night-waking, no use of rescue medication. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	86	86	91	79	109	66	93
Units: percent
least squares mean (confidence interval 95%)	15.470 (9.547 to 21.394)	11.362 (5.435 to 17.290)	12.646 (6.865 to 18.427)	15.925 (9.775 to 22.076)	14.479 (8.896 to 20.062)	5.859 (-0.813 to 12.532)	13.037 (7.301 to 18.772)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

9.611

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

18.042

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.503

Confidence interval

level

95%

sides

2-sided

lower limit

-2.927

upper limit

13.933

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.11

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.787

Confidence interval

level

95%

sides

2-sided

lower limit

-1.546

upper limit

15.119

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.066

Confidence interval

level

95%

sides

2-sided

lower limit

1.461

upper limit

18.672

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.038

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

8.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.489

upper limit

16.75

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority ^[20]

P-value

= 0.09

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.178

Confidence interval

level

95%

sides

2-sided

lower limit

-1.112

upper limit

15.467

Notes
[20] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in percent rescue-free days over the Treatment Period

Top of page

End point title

Change from baseline in percent rescue-free days over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). A rescue-free day (RFD) was defined as a day with no use of rescue medication. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	86	86	91	79	109	66	93
Units: percent
least squares mean (confidence interval 95%)	31.138 (24.019 to 38.257)	24.178 (17.045 to 31.312)	21.960 (14.940 to 28.980)	34.991 (27.549 to 42.433)	30.775 (24.025 to 37.526)	23.202 (15.188 to 31.215)	28.260 (21.308 to 35.211)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.123

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.936

Confidence interval

level

95%

sides

2-sided

lower limit

-2.16

upper limit

18.031

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.849

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.977

Confidence interval

level

95%

sides

2-sided

lower limit

-9.112

upper limit

11.065

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.807

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.242

Confidence interval

level

95%

sides

2-sided

lower limit

-11.233

upper limit

8.748

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.025

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.789

Confidence interval

level

95%

sides

2-sided

lower limit

1.488

upper limit

22.09

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.127

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.574

Confidence interval

level

95%

sides

2-sided

lower limit

-2.16

upper limit

17.307

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.318

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.058

Confidence interval

level

95%

sides

2-sided

lower limit

-4.874

upper limit

14.99

Notes
[21] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Change from baseline in percent symptom-free days over the Treatment Period

Top of page

End point title

Change from baseline in percent symptom-free days over the Treatment Period

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Days without asthma symptoms, or symptom-free days, were defined as days without asthma symptoms, short-acting β-agonist (SABA) use, systemic corticosteroid use, or need for urgent asthma care.

End point type

Secondary

End point timeframe

Week 0 (7 days prior to randomisation) to Week 12

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	86	86	91	79	109	66	93
Units: percent
least squares mean (confidence interval 95%)	13.780 (7.873 to 19.686)	10.521 (4.608 to 16.435)	11.935 (6.169 to 17.701)	14.673 (8.539 to 20.806)	13.451 (7.883 to 19.018)	3.329 (-3.319 to 9.977)	14.018 (8.293 to 19.743)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.45

Confidence interval

level

95%

sides

2-sided

lower limit

2.046

upper limit

18.855

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.093

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.192

Confidence interval

level

95%

sides

2-sided

lower limit

-1.208

upper limit

15.592

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.042

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

8.606

Confidence interval

level

95%

sides

2-sided

lower limit

0.298

upper limit

16.913

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.344

Confidence interval

level

95%

sides

2-sided

lower limit

2.773

upper limit

19.914

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.122

Confidence interval

level

95%

sides

2-sided

lower limit

2.021

upper limit

18.222

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

= 0.011

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.689

Confidence interval

level

95%

sides

2-sided

lower limit

2.424

upper limit

18.953

Notes
[22] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Time to recurrent Composite endpoint for severe exacerbations of asthma (CompEx) event

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End point title

Time to recurrent Composite endpoint for severe exacerbations of asthma (CompEx) event

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). CompEx is a composite endpoint combining severe exacerbations of asthma and diary events. CompEx is a composite surrogate endpoint for severe exacerbations of asthma, recently developed by AstraZeneca (it is not yet a regulatory-approved clinical endpoint). Severe exacerbations are defined as those episodes that lead to hospitalisation, emergency room visit and/or treatment with oral corticosteroids. Time at risk was calculated as [(date of last treatment – date of randomisation)+1 – recovery time. Recovery time was the sum (from i=1 to k) of (min with event end date +7, date of last treatment] – with event start date +1). No statistical analysis is done for this endpoint.

End point type

Secondary

End point timeframe

From Screening (Within 21-28 days before randomisation) to Week 12/End of treatment or Early Termination Visit

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	110	112	111	113	134	113	112
Units: Years
number (not applicable)	21.3	22.2	22.6	23.1	29.0	18.6	24.4

No statistical analyses for this end point

Secondary: Annualized CompEx event rate

Top of page

End point title

Annualized CompEx event rate

End point description

To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). CompEx is a composite endpoint combining severe exacerbations of asthma and diary events. CompEx is a composite surrogate endpoint for severe exacerbations of asthma, recently developed by AstraZeneca (it is not yet a regulatory-approved clinical endpoint). Severe exacerbations are defined as those episodes that lead to hospitalisation, emergency room visit and/or treatment with oral corticosteroids. CompEx Model: Rates, rate ratios, and p-values were from a negative binomial model analysis, with event count as the dependent variable, with treatment and region as covariates and log-transformed time at risk (days) as an offset variable to account for overdispersion.

End point type

Secondary

End point timeframe

From Screening (Within 21-28 days before randomisation) to Week 12/End of treatment or Early Termination Visit

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	110	112	111	113	134	113	112
Units: Annual rate
number (not applicable)	2.06	2.20	2.04	0.67	0.50	4.71	0.75

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.035

Method

Negative Binominal Model

Parameter type

Estimate

Point estimate

0.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.94

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05

Method

Negative Binominal Model

Parameter type

Estimate

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.22

upper limit

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032

Method

Negative Binominal Model

Parameter type

Estimate

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.93

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Negative Binominal Model

Parameter type

Estimate

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.34

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

247

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Negative Binominal Model

Parameter type

Estimate

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

0.25

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

< 0.001

Method

Negative Binominal Model

Parameter type

Estimate

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

0.37

Notes
[23] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Observed maximum concentration at steady state (Css,max) of AZD7594 at Day 84

Top of page

End point title

Observed maximum concentration at steady state (Css,max) of AZD7594 at Day 84

End point description

To describe the (steady state) pharmacokinetic (PK) of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter.

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 hour (h) post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	17	14	15	16	27	0 ^[24]	0 ^[25]
Units: pmol/L
geometric mean (geometric coefficient of variation)	48.45 ( 68.65 )	114.90 ( 99.12 )	69.71 ( 105.94 )	154.50 ( 144.67 )	200.00 ( 113.05 )	( )	( )

Notes
[24] - Subjects from this arm were excluded from the PK analysis set.
[25] - Subjects from this arm were excluded from the PK analysis set.

Statistical Analysis 1

Statistical analysis description

Assessment of Dose Proportionality of AZD7594 PK Parameter at Visit 7 (Day 84) (PK Analysis Set)

Comparison groups

AZD7594 50 μg v AZD7594 90 μg v AZD7594 180 μg v AZD7594 360 μg v AZD7594 720 μg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Slope

Point estimate

0.476

Confidence interval

level

90%

sides

2-sided

lower limit

0.321

upper limit

0.632

Variability estimate

Standard error of the mean

Dispersion value

0.094

Secondary: Observed minimum concentration at the end of the dosing interval (Css,min) of AZD7594 at Day 84

Top of page

End point title

Observed minimum concentration at the end of the dosing interval (Css,min) of AZD7594 at Day 84

End point description

To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint.

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	3	10	11	13	26	0 ^[26]	0 ^[27]
Units: pmol/L
geometric mean (geometric coefficient of variation)	14.41 ( 37.59 )	21.45 ( 43.12 )	30.22 ( 43.28 )	70.58 ( 46.22 )	85.13 ( 108.41 )	( )	( )

Notes
[26] - Subjects from this arm were excluded from the PK analysis set.
[27] - Subjects from this arm were excluded from the PK analysis set.

No statistical analyses for this end point

Secondary: Time to maximum concentration at steady state, taken directly from the individual concentration-time curve (tss, max) of AZD7594 at Day 84

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End point title

Time to maximum concentration at steady state, taken directly from the individual concentration-time curve (tss, max) of AZD7594 at Day 84

End point description

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	17	14	15	16	27	0 ^[28]	0 ^[29]
Units: hours
median (full range (min-max))	0.25 (0.23 to 2.17)	0.25 (0.00 to 0.98)	0.25 (0.20 to 2.00)	0.25 (0.00 to 2.00)	0.25 (0.00 to 23.98)	( to )	( to )

Notes
[28] - Subjects from this arm were excluded from the PK analysis set.
[29] - Subjects from this arm were excluded from the PK analysis set.

No statistical analyses for this end point

Secondary: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD7594 at Day 84

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End point title

Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD7594 at Day 84

End point description

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	15	14	14	16	26	0 ^[30]	0 ^[31]
Units: h*pmol/L
geometric mean (geometric coefficient of variation)	167.50 ( 123.50 )	573.00 ( 116.00 )	719.10 ( 134.58 )	1435.00 ( 140.28 )	2622.00 ( 98.88 )	( )	( )

Notes
[30] - Subjects from this arm were excluded from the PK analysis set.
[31] - Subjects from this arm were excluded from the PK analysis set.

No statistical analyses for this end point

Secondary: Area under the plasma concentration-curve within a dosing interval (AUCτ) of AZD7594 at Day 84

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End point title

Area under the plasma concentration-curve within a dosing interval (AUCτ) of AZD7594 at Day 84

End point description

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	3	10	11	13	26	0 ^[32]	0 ^[33]
Units: h*pmol/L
geometric mean (geometric coefficient of variation)	530.50 ( 32.57 )	928.60 ( 37.52 )	1137.00 ( 52.06 )	2205.00 ( 52.32 )	2622.00 ( 98.88 )	( )	( )

Notes
[32] - Subjects from this arm were excluded from the PK analysis set.
[33] - Subjects from this arm were excluded from the PK analysis set.

Statistical Analysis 1

Statistical analysis description

Assessment of Dose Proportionality of AZD7594 PK Parameter at Visit 7 (Day 84) (PK Analysis Set)

Comparison groups

AZD7594 50 μg v AZD7594 90 μg v AZD7594 180 μg v AZD7594 360 μg v AZD7594 720 μg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Slope

Point estimate

0.555

Confidence interval

level

90%

sides

2-sided

lower limit

0.402

upper limit

0.709

Variability estimate

Standard error of the mean

Dispersion value

0.092

Secondary: Average plasma concentration during a dosing interval at steady state (Css,avg) of AZD7594 at Day 84

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End point title

Average plasma concentration during a dosing interval at steady state (Css,avg) of AZD7594 at Day 84

End point description

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	3	10	11	13	26	0 ^[34]	0 ^[35]
Units: pmol/L
geometric mean (geometric coefficient of variation)	22.10 ( 32.57 )	38.69 ( 37.52 )	47.37 ( 52.06 )	91.86 ( 52.32 )	109.30 ( 98.88 )	( )	( )

Notes
[34] - Subjects from this arm were excluded from the PK analysis set.
[35] - Subjects from this arm were excluded from the PK analysis set.

No statistical analyses for this end point

Secondary: Dose normalised Css,max (Css,max/D) of AZD7594 at Day 84

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End point title

Dose normalised Css,max (Css,max/D) of AZD7594 at Day 84

End point description

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	17	14	15	16	27	0 ^[36]	0 ^[37]
Units: pmol/L/umol
geometric mean (geometric coefficient of variation)	587.80 ( 68.65 )	774.40 ( 99.12 )	234.90 ( 105.94 )	260.40 ( 144.67 )	168.50 ( 113.05 )	( )	( )

Notes
[36] - Subjects from this arm were excluded from the PK analysis set.
[37] - Subjects from this arm were excluded from the PK analysis set.

No statistical analyses for this end point

Secondary: Dose normalised AUCτ (AUCτ/D) of AZD7594 at Day 84

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End point title

Dose normalised AUCτ (AUCτ/D) of AZD7594 at Day 84

End point description

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	3	10	11	13	26	0 ^[38]	0 ^[39]
Units: h*pmol/μmol
geometric mean (geometric coefficient of variation)	6436.00 ( 32.57 )	6259.00 ( 37.52 )	3831.00 ( 52.06 )	3715.00 ( 52.32 )	2209.00 ( 98.88 )	( )	( )

Notes
[38] - Subjects from this arm were excluded from the PK analysis set.
[39] - Subjects from this arm were excluded from the PK analysis set.

No statistical analyses for this end point

Secondary: Percentage Fluctuation index within a dosing interval of AZD7594 at Day 84

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End point title

Percentage Fluctuation index within a dosing interval of AZD7594 at Day 84

End point description

End point type

Secondary

End point timeframe

Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	3	10	11	13	26	0 ^[40]	0 ^[41]
Units: percentage
geometric mean (geometric coefficient of variation)	387.80 ( 21.97 )	326.60 ( 37.40 )	148.90 ( 38.27 )	172.10 ( 44.32 )	98.22 ( 61.36 )	( )	( )

Notes
[40] - Subjects from this arm were excluded from the PK analysis set.
[41] - Subjects from this arm were excluded from the PK analysis set.

No statistical analyses for this end point

Secondary: Change from baseline of area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC0-24), compared to Placebo of AZD7594 at Day 84

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End point title

Change from baseline of area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC0-24), compared to Placebo of AZD7594 at Day 84

End point description

To describe the pharmacodynamics of AZD7594 by measuring cortisol suppression in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (Pharmacodynamic Analysis Set). Baseline was defined as the Day -1 value. Analyses were based on an ANCOVA model with change from baseline on the log-scale as the response, treatment as a fixed effect, and log-transformed baseline value as a covariate.

End point type

Secondary

End point timeframe

Day 84 (at 0 [pre-dose], 2, 4, 6, 8, 10, 12, 16, 20, 22 and 24 hours relative to IP administration)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	19	16	16	17	27	14	17
Units: ng/mL
geometric mean (confidence interval 95%)	1.029 (0.920 to 1.152)	1.140 (1.009 to 1.287)	1.151 (1.018 to 1.300)	1.003 (0.891 to 1.129)	0.934 (0.850 to 1.026)	1.019 (0.895 to 1.161)	1.011 (0.898 to 1.137)

Statistical Analysis 1

Comparison groups

AZD7594 50 μg v Placebo to AZD7594

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.909

Method

ANCOVA

Parameter type

geometric LSMean ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.851

upper limit

1.199

Statistical Analysis 2

Comparison groups

AZD7594 90 μg v Placebo to AZD7594

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.218

Method

ANCOVA

Parameter type

geometric LSMean ratio

Point estimate

1.118

Confidence interval

level

95%

sides

2-sided

lower limit

0.935

upper limit

1.336

Statistical Analysis 3

Comparison groups

AZD7594 180 μg v Placebo to AZD7594

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.181

Method

ANCOVA

Parameter type

geometric LSMean ratio

Point estimate

1.129

Confidence interval

level

95%

sides

2-sided

lower limit

0.944

upper limit

1.349

Statistical Analysis 4

Comparison groups

AZD7594 360 μg v Placebo to AZD7594

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.859

Method

ANCOVA

Parameter type

geometric LSMean ratio

Point estimate

0.984

Confidence interval

level

95%

sides

2-sided

lower limit

0.825

upper limit

1.174

Statistical Analysis 5

Comparison groups

AZD7594 720 μg v Placebo to AZD7594

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.285

Method

ANCOVA

Parameter type

geometric LSMean ratio

Point estimate

0.916

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.077

Statistical Analysis 6

Comparison groups

Placebo to AZD7594 v Fluticasone furoate

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[42]

P-value

= 0.923

Method

ANCOVA

Parameter type

geometric LSMean ratio

Point estimate

0.991

Confidence interval

level

95%

sides

2-sided

lower limit

0.831

upper limit

1.182

Notes
[42] - The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo

Secondary: Number of subjects with adverse events

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End point title

Number of subjects with adverse events

End point description

To evaluate the safety and tolerability of AZD7594 in relation to Placebo in asthmatics symptomatic on low dose ICS (Safety Analysis Set). No statistical analysis is done for this endpoint.

End point type

Secondary

End point timeframe

From screening to follow-up period (7 to 10 days after visit 7)

End point values	AZD7594 50 μg	AZD7594 90 μg	AZD7594 180 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Number of subjects analysed	110	112	111	113	134	113	112
Units: Subjects
Any AE	35	45	39	54	46	47	34
death	0	0	0	1	0	0	0
Any SAE	0	3	1	3	3	0	1
Any AE leading to discontinuation of IP	6	8	4	11	4	20	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Screening to follow-up period (7to 10 days after visit 7)

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

AZD7594 50 μg

Reporting group description

Oral inhalation of AZD5794 55 microgram/ 50 microgram (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 180 μg

Reporting group description

Oral inhalation of AZD5794 198 microgram/ 180 microgram (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 90 μg

Reporting group description

Oral inhalation of AZD5794 99 microgram/ 90 microgram (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 360 μg

Reporting group description

Oral inhalation of AZD5794 396 microgram/ 360 microgram (nominal dose/delivered dose) once daily.

Reporting group title

AZD7594 720 μg

Reporting group description

Oral inhalation of AZD5794 792 microgram/ 720 microgram (nominal dose/delivered dose) once daily.

Reporting group title

Placebo to AZD7594

Reporting group description

Oral inhalation of placebo to AZD7594 once daily.

Reporting group title

Fluticasone furoate

Reporting group description

Oral inhalation of fluticasone furoate 100 microgram once daily.

Serious adverse events	AZD7594 50 μg	AZD7594 180 μg	AZD7594 90 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 110 (0.00%)	1 / 111 (0.90%)	3 / 112 (2.68%)	3 / 113 (2.65%)	3 / 134 (2.24%)	0 / 113 (0.00%)	1 / 112 (0.89%)
number of deaths (all causes)	0	0	0	1	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 112 (0.00%)	0 / 113 (0.00%)	1 / 134 (0.75%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 112 (0.00%)	0 / 113 (0.00%)	1 / 134 (0.75%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 112 (0.00%)	0 / 113 (0.00%)	1 / 134 (0.75%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 112 (0.00%)	0 / 113 (0.00%)	0 / 134 (0.00%)	0 / 113 (0.00%)	1 / 112 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 112 (0.00%)	1 / 113 (0.88%)	0 / 134 (0.00%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 112 (0.00%)	1 / 113 (0.88%)	0 / 134 (0.00%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 110 (0.00%)	1 / 111 (0.90%)	1 / 112 (0.89%)	1 / 113 (0.88%)	0 / 134 (0.00%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	1 / 112 (0.89%)	0 / 113 (0.00%)	0 / 134 (0.00%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	1 / 112 (0.89%)	0 / 113 (0.00%)	0 / 134 (0.00%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neck pain
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	1 / 112 (0.89%)	0 / 113 (0.00%)	0 / 134 (0.00%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Sepsis
subjects affected / exposed	0 / 110 (0.00%)	0 / 111 (0.00%)	1 / 112 (0.89%)	0 / 113 (0.00%)	0 / 134 (0.00%)	0 / 113 (0.00%)	0 / 112 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	AZD7594 50 μg	AZD7594 180 μg	AZD7594 90 μg	AZD7594 360 μg	AZD7594 720 μg	Placebo to AZD7594	Fluticasone furoate
Total subjects affected by non serious adverse events
subjects affected / exposed	14 / 110 (12.73%)	8 / 111 (7.21%)	15 / 112 (13.39%)	14 / 113 (12.39%)	8 / 134 (5.97%)	24 / 113 (21.24%)	11 / 112 (9.82%)
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	7 / 110 (6.36%)	2 / 111 (1.80%)	6 / 112 (5.36%)	10 / 113 (8.85%)	3 / 134 (2.24%)	19 / 113 (16.81%)	3 / 112 (2.68%)
occurrences all number	7	2	6	10	3	20	3
Infections and infestations
Nasopharyngitis
subjects affected / exposed	7 / 110 (6.36%)	6 / 111 (5.41%)	9 / 112 (8.04%)	4 / 113 (3.54%)	5 / 134 (3.73%)	6 / 113 (5.31%)	9 / 112 (8.04%)
occurrences all number	7	6	9	4	6	6	9

More information

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Were there any global substantial amendments to the protocol? Yes

26 Apr 2019

Deletion of peak FEV1 from the secondary efficacy endpoints. Update of the inclusion criteria to include only subjects with BMI ≤ 35. Deletion of the expected number of subjects in the US vs. non-US sites. Removal of interim futility analysis. Specification of inclusion criterion #7 (pre-bronchodilator FEV1 at Visit 3 between 40% and 90% predicted). Deletion of QT interval corrected using Bazett’s formula; addition of appropriate electrocardiogram parameters. Clarification of exclusion criterion #3 and exclusion criterion #21 for alcohol and drug abuse. Clarified the required treatments for postmenopausal subjects. Clarified that the subjects were discontinued when specified criteria are met. Deletion of measure peak expiratory flow at Screening. Clarification of the number of measurement and timing of spirometry. Clarification of the compliance rate in the Run-in Period and the expected compliance rate in the Treatment Period. Clarification that peak expiratory flow was measured at home after completing the morning and evening diary. Clarification that Forced oscillation technique evaluation and training took place at Visit 1, instead of Visit 2. Deletion of the description that rescue medication should be recorded as concomitant medication. Clarification that the analysis set used for demographic and baseline characteristics was Full analysis set. Clarification that baseline asthma severity was assessed using the pre-SABA value at Visit 2, instead of pre-bronchodilator value at Visit 1. The number of subjects who met the reversibility criteria was deleted. “Individual plasma concentrations vs. time on Week 12 (Day 84) plotted on linear and semi-logarithmic scale with all treatments overlaid on the same plot and separate plots for each subject” was no longer provided as part of PK analysis. Geometric SD was no longer presented on figures of geometric mean for concentration-time data as part of the PK analysis. Clarification of the definition of ACQ-5 responder.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Parallel Arm, Multi-Centre Study to Assess Efficacy and Safety of Multiple Dose Levels of AZD7594 DPI Given Once Daily for Twelve Weeks, Compared to Placebo, in Asthmatics Symptomatic on Low Dose ICS

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline in trough Forced expiratory volume in 1 second (FEV1) at Week 12

Primary: Change from baseline in trough Forced expiratory volume in 1 second (FEV1) at Week 12

Secondary: Change from baseline in trough FEV1 at Weeks 2, 4, 8 and average over the Treatment Period

Secondary: Change from baseline in trough FEV1 at Weeks 2, 4, 8 and average over the Treatment Period

Secondary: Change from baseline in Fractional exhaled nitic oxide (FENO) at Weeks 2, 4, 8, 12 and average over the Treatment Period

Secondary: Change from baseline in Fractional exhaled nitic oxide (FENO) at Weeks 2, 4, 8, 12 and average over the Treatment Period

Secondary: Change from baseline in trough Forced vital capacity (FVC) at Week 12 and average over the Treatment Period

Secondary: Change from baseline in trough Forced vital capacity (FVC) at Week 12 and average over the Treatment Period

Secondary: Change from baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and average over the Treatment Period

Secondary: Change from baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and average over the Treatment Period

Secondary: Change from baseline in average morning Peak Expiratory Flow (PEF) over the Treatment Period

Secondary: Change from baseline in average morning Peak Expiratory Flow (PEF) over the Treatment Period

Secondary: Change from baseline in average evening PEF over the Treatment Period

Secondary: Change from baseline in average evening PEF over the Treatment Period

Secondary: Change from baseline in average daily use of rescue medication over the Treatment Period

Secondary: Change from baseline in average daily use of rescue medication over the Treatment Period

Secondary: Change from baseline in percent night-time awakening days over the Treatment Period

Secondary: Change from baseline in percent night-time awakening days over the Treatment Period

Secondary: Change from baseline in average daily asthma symptom score over the Treatment Period

Secondary: Change from baseline in average daily asthma symptom score over the Treatment Period

Secondary: Change from baseline in percent asthma control days over the Treatment Period

Secondary: Change from baseline in percent asthma control days over the Treatment Period

Secondary: Change from baseline in percent rescue-free days over the Treatment Period

Secondary: Change from baseline in percent rescue-free days over the Treatment Period

Secondary: Change from baseline in percent symptom-free days over the Treatment Period

Secondary: Change from baseline in percent symptom-free days over the Treatment Period

Secondary: Time to recurrent Composite endpoint for severe exacerbations of asthma (CompEx) event

Secondary: Time to recurrent Composite endpoint for severe exacerbations of asthma (CompEx) event

Secondary: Annualized CompEx event rate

Secondary: Annualized CompEx event rate

Secondary: Observed maximum concentration at steady state (Css,max) of AZD7594 at Day 84

Secondary: Observed maximum concentration at steady state (Css,max) of AZD7594 at Day 84

Secondary: Observed minimum concentration at the end of the dosing interval (Css,min) of AZD7594 at Day 84

Secondary: Observed minimum concentration at the end of the dosing interval (Css,min) of AZD7594 at Day 84

Secondary: Time to maximum concentration at steady state, taken directly from the individual concentration-time curve (tss, max) of AZD7594 at Day 84

Secondary: Time to maximum concentration at steady state, taken directly from the individual concentration-time curve (tss, max) of AZD7594 at Day 84

Secondary: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD7594 at Day 84

Secondary: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD7594 at Day 84

Secondary: Area under the plasma concentration-curve within a dosing interval (AUCτ) of AZD7594 at Day 84

Secondary: Area under the plasma concentration-curve within a dosing interval (AUCτ) of AZD7594 at Day 84

Secondary: Average plasma concentration during a dosing interval at steady state (Css,avg) of AZD7594 at Day 84

Secondary: Average plasma concentration during a dosing interval at steady state (Css,avg) of AZD7594 at Day 84

Secondary: Dose normalised Css,max (Css,max/D) of AZD7594 at Day 84

Secondary: Dose normalised Css,max (Css,max/D) of AZD7594 at Day 84

Secondary: Dose normalised AUCτ (AUCτ/D) of AZD7594 at Day 84

Secondary: Dose normalised AUCτ (AUCτ/D) of AZD7594 at Day 84

Secondary: Percentage Fluctuation index within a dosing interval of AZD7594 at Day 84

Secondary: Percentage Fluctuation index within a dosing interval of AZD7594 at Day 84

Secondary: Change from baseline of area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC0-24), compared to Placebo of AZD7594 at Day 84

Secondary: Change from baseline of area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC0-24), compared to Placebo of AZD7594 at Day 84

Secondary: Number of subjects with adverse events

Secondary: Number of subjects with adverse events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Parallel Arm, Multi-Centre Study to Assess Efficacy and Safety of Multiple Dose Levels of AZD7594 DPI Given Once Daily for Twelve Weeks, Compared to Placebo, in Asthmatics Symptomatic on Low Dose ICS