Clinical Trial Results:
A Phase 2b Randomised, DoubleBlind, PlaceboControlled, Parallel Arm, MultiCentre 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 
201700248340 
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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
D3741C00007


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT03622112  
WHO universal trial number (UTN) 
  
Sponsors


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


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


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


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


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
21 Nov 2019


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
30 Sep 2019


Was the trial ended prematurely? 
No


General information about the trial


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 countryspecific 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 followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


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 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
630


From 65 to 84 years 
176


85 years and over 
0



Recruitment


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.  
Preassignment


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


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  
Arms


Are arms mutually exclusive 
Yes


Arm title

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


Arm title

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


Arm title

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


Arm title

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


Arm title

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)


Arm title

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


Arm title

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




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 reporting groups


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.  



End points reporting groups


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. 


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) predose 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 Mixedeffects 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




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
153


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.437  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.036


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.126  
upper limit 
0.054  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.236  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.054


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.143  
upper limit 
0.035  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
162


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.389  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.039


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.05  
upper limit 
0.128  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.094  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.076


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.013  
upper limit 
0.165  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
193


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.06  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.082


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.003  
upper limit 
0.167  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
173


Analysis specification 
Prespecified


Analysis type 
superiority ^{[1]}  
Pvalue 
= 0.014  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.111


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.023  
upper limit 
0.199  
Notes [1]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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) predose 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




Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.463  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.029


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.048  
upper limit 
0.105  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.576  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.022


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.055  
upper limit 
0.098  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.047  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.078


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.001  
upper limit 
0.154  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.009  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.102


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.025  
upper limit 
0.179  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
227


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.104


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.031  
upper limit 
0.178  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
204


Analysis specification 
Prespecified


Analysis type 
superiority ^{[2]}  
Pvalue 
= 0.003  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.118


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.685  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.018


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.068  
upper limit 
0.103  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.176  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.059


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.026  
upper limit 
0.144  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.024  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.098


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.013  
upper limit 
0.183  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.106


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.021  
upper limit 
0.191  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
227


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.114


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.032  
upper limit 
0.196  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
204


Analysis specification 
Prespecified


Analysis type 
superiority ^{[3]}  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.165


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.707  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.017


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.072  
upper limit 
0.106  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.904  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.005


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.083  
upper limit 
0.094  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.121  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.018  
upper limit 
0.157  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.026  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.012  
upper limit 
0.188  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
227


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.139


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.055  
upper limit 
0.224  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
204


Analysis specification 
Prespecified


Analysis type 
superiority ^{[4]}  
Pvalue 
= 0.006  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.122


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.856  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.007


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.068  
upper limit 
0.081  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.832  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.008


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.066  
upper limit 
0.082  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
203


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.06  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.071


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.003  
upper limit 
0.145  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.011  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.096


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.022  
upper limit 
0.17  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
227


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.039  
upper limit 
0.181  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
204


Analysis specification 
Prespecified


Analysis type 
superiority ^{[5]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.129


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.055  
upper limit 
0.202  
Notes [5]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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 logscale as the response, treatment, visit, treatment by visit interaction and region as fixed effects, and logtransformed 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




Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.322  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.936


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.822  
upper limit 
1.067  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.047  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.876


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.768  
upper limit 
0.999  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.01  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.842


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.739  
upper limit 
0.959  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.825


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.724  
upper limit 
0.941  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
222


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.687


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.606  
upper limit 
0.779  
Statistical analysis title 
Statistical Analysis at Week 2  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority ^{[6]}  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.63


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.329  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.931


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.805  
upper limit 
1.076  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.203  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.911


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.789  
upper limit 
1.052  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.273  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.923


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1.065  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.023  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.846


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.734  
upper limit 
0.977  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
222


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.742


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.646  
upper limit 
0.852  
Statistical analysis title 
Statistical Analysis at Week 4  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority ^{[7]}  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.703


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.283  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.917


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.783  
upper limit 
1.074  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.386  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.933


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.797  
upper limit 
1.092  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.126  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.886


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.758  
upper limit 
1.035  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.05  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.855


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.731  
upper limit 
1  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
222


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.723


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.623  
upper limit 
0.84  
Statistical analysis title 
Statistical Analysis at Week 8  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority ^{[8]}  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.642


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.359  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.927


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.789  
upper limit 
1.09  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
Placebo to AZD7594 v AZD7594 90 μg


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.556  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.953


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.813  
upper limit 
1.118  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.084  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.869


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.742  
upper limit 
1.019  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.011  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.813


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.693  
upper limit 
0.953  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
222


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.559  
upper limit 
0.757  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority ^{[9]}  
Pvalue 
< 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.623


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.231  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.928


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.821  
upper limit 
1.049  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.17  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.918


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.812  
upper limit 
1.037  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
202


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.039  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.879


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.778  
upper limit 
0.994  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.835


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.739  
upper limit 
0.943  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
222


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.622  
upper limit 
0.787  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
199


Analysis specification 
Prespecified


Analysis type 
superiority ^{[10]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.649


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.575  
upper limit 
0.732  
Notes [10]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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) predose 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




Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
153


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.519  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.034


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.139  
upper limit 
0.07  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.141  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.078


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.181  
upper limit 
0.026  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
162


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.772  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.015


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.088  
upper limit 
0.119  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.27  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.058


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.045  
upper limit 
0.162  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
193


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.592  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.027


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.072  
upper limit 
0.126  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
173


Analysis specification 
Prespecified


Analysis type 
superiority ^{[11]}  
Pvalue 
= 0.275  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.057


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
153


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.963  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.002


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.087  
upper limit 
0.083  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.533  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.027


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.112  
upper limit 
0.058  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
162


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.342  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.041


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.044  
upper limit 
0.126  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.061  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.081


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.004  
upper limit 
0.165  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
193


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.278  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.045


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.037  
upper limit 
0.127  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
173


Analysis specification 
Prespecified


Analysis type 
superiority ^{[12]}  
Pvalue 
= 0.079  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.075


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.009  
upper limit 
0.159  
Notes [12]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


End point title 
Change from baseline in Asthma Control Questionnaire 5 (ACQ5) 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 ACQ5 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 ACQ5 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




Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
153


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.088  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.153


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.328  
upper limit 
0.023  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
161


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.257


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
0.084  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
163


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.221


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.393  
upper limit 
0.049  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.029  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.193


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.366  
upper limit 
0.02  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
192


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.269


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.434  
upper limit 
0.104  
Statistical analysis title 
Statistical Analysis at Week 12  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
173


Analysis specification 
Prespecified


Analysis type 
superiority ^{[13]}  
Pvalue 
= 0.01  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.223


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
153


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.055  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.125


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.253  
upper limit 
0.003  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
161


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.029  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.141


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.268  
upper limit 
0.014  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
163


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.044  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.257  
upper limit 
0.003  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
160


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.201


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.328  
upper limit 
0.074  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
192


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.217


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.339  
upper limit 
0.094  
Statistical analysis title 
Statistical Analysis for Treatment period average  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
173


Analysis specification 
Prespecified


Analysis type 
superiority ^{[14]}  
Pvalue 
= 0.005  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.179


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.305  
upper limit 
0.053  
Notes [14]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


End point title 
Change from baseline in average morning Peak Expiratory Flow (PEF) 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.


End point type 
Secondary


End point timeframe 
Week 0 (7 days prior to randomisation) to Week 12




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
162


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.097  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.664


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.403  
upper limit 
16.73  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
167


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.19  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.981


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.98  
upper limit 
14.941  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
170


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.045  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
9.123


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.195  
upper limit 
18.052  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
165


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
15.444


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.443  
upper limit 
24.445  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
195


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
16.599


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.031  
upper limit 
25.167  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
177


Analysis specification 
Prespecified


Analysis type 
superiority ^{[15]}  
Pvalue 
= 0.019  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
10.491


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.726  
upper limit 
19.256  
Notes [15]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


End point title 
Change from baseline in average evening PEF 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.


End point type 
Secondary


End point timeframe 
Week 0 (7 days prior to randomisation) to Week 12




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
161


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.597  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.398


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.494  
upper limit 
11.29  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
166


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.629  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.162


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.623  
upper limit 
10.948  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
169


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.389  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.833


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.907  
upper limit 
12.573  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
165


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.022  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
10.258


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.456  
upper limit 
19.059  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
192


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
11.994


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.571  
upper limit 
20.417  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
175


Analysis specification 
Prespecified


Analysis type 
superiority ^{[16]}  
Pvalue 
= 0.163  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6.129


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.479  
upper limit 
14.737  
Notes [16]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


End point title 
Change from baseline in average daily use of rescue medication 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.


End point type 
Secondary


End point timeframe 
Week 0 (7 days prior to randomisation) to Week 12




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.243


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.431  
upper limit 
0.054  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.108  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.155


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.344  
upper limit 
0.034  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
157


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.295  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.099


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.286  
upper limit 
0.087  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
145


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.308


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.116  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
175


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.308


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.489  
upper limit 
0.126  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
159


Analysis specification 
Prespecified


Analysis type 
superiority ^{[17]}  
Pvalue 
= 0.062  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.177


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.362  
upper limit 
0.009  
Notes [17]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


End point title 
Change from baseline in percent nighttime awakening 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). 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




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
162


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
9.993


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
15.795  
upper limit 
4.191  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
167


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.972


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.694  
upper limit 
2.251  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
170


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.133  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.361


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.051  
upper limit 
1.329  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
165


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.008  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.797


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
13.555  
upper limit 
2.04  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
195


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.729


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
14.195  
upper limit 
3.264  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
177


Analysis specification 
Prespecified


Analysis type 
superiority ^{[18]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
11.622


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
17.211  
upper limit 
6.034  
Notes [18]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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 Runin and Treatment Periods, subjects recorded the severity of their asthma symptoms during nighttime and daytime each morning and evening, using the eDiary. Asthma symptom scores during nighttime/daytime 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




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.212


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.329  
upper limit 
0.094  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.066  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.228  
upper limit 
0.007  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
157


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.02  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.139


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.255  
upper limit 
0.022  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
145


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.35  
upper limit 
0.11  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
175


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.185


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.298  
upper limit 
0.071  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
159


Analysis specification 
Prespecified


Analysis type 
superiority ^{[19]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.206


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.321  
upper limit 
0.09  
Notes [19]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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). Asthmacontrol days was defined as days with no symptoms, no nightwaking, 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




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.026  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
9.611


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.18  
upper limit 
18.042  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.503


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.927  
upper limit 
13.933  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
157


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.11  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6.787


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.546  
upper limit 
15.119  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
145


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.022  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
10.066


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.461  
upper limit 
18.672  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
175


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.038  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.489  
upper limit 
16.75  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
159


Analysis specification 
Prespecified


Analysis type 
superiority ^{[20]}  
Pvalue 
= 0.09  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.178


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.112  
upper limit 
15.467  
Notes [20]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


End point title 
Change from baseline in percent rescuefree 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 rescuefree 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




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.123  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.936


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.16  
upper limit 
18.031  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.849  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.977


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.112  
upper limit 
11.065  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
157


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.807  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.242


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.233  
upper limit 
8.748  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
145


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.025  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
11.789


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.488  
upper limit 
22.09  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
175


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.127  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.574


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.16  
upper limit 
17.307  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
159


Analysis specification 
Prespecified


Analysis type 
superiority ^{[21]}  
Pvalue 
= 0.318  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.058


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.874  
upper limit 
14.99  
Notes [21]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


End point title 
Change from baseline in percent symptomfree 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 symptomfree days, were defined as days without asthma symptoms, shortacting βagonist (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




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.015  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
10.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.046  
upper limit 
18.855  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
152


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.093  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.192


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.208  
upper limit 
15.592  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
157


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.042  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.606


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.298  
upper limit 
16.913  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
145


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.01  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
11.344


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.773  
upper limit 
19.914  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
175


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
10.122


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.021  
upper limit 
18.222  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
159


Analysis specification 
Prespecified


Analysis type 
superiority ^{[22]}  
Pvalue 
= 0.011  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
10.689


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.424  
upper limit 
18.953  
Notes [22]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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 regulatoryapproved 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 2128 days before randomisation) to Week 12/End of treatment or Early Termination Visit




No statistical analyses for this end point 


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 regulatoryapproved 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 pvalues were from a negative binomial model analysis, with event count as the dependent variable, with treatment and
region as covariates and logtransformed time at risk (days) as an offset variable to account for overdispersion.


End point type 
Secondary


End point timeframe 
From Screening (Within 2128 days before randomisation) to Week 12/End of treatment or Early Termination Visit




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
223


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.035  
Method 
Negative Binominal Model  
Parameter type 
Estimate  
Point estimate 
0.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.94  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
225


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.05  
Method 
Negative Binominal Model  
Parameter type 
Estimate  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.22  
upper limit 
1  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
224


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.032  
Method 
Negative Binominal Model  
Parameter type 
Estimate  
Point estimate 
0.43


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.93  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
226


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Negative Binominal Model  
Parameter type 
Estimate  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.06  
upper limit 
0.34  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
247


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Negative Binominal Model  
Parameter type 
Estimate  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.04  
upper limit 
0.25  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
225


Analysis specification 
Prespecified


Analysis type 
superiority ^{[23]}  
Pvalue 
< 0.001  
Method 
Negative Binominal Model  
Parameter type 
Estimate  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.07  
upper limit 
0.37  
Notes [23]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 hour (h) postdose)




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 title 
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 
89


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Slope  
Point estimate 
0.476


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.321  
upper limit 
0.632  
Variability estimate 
Standard error of the mean


Dispersion value 
0.094



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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 


End point title 
Time to maximum concentration at steady state, taken directly from the individual concentrationtime curve (tss, max) 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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 


End point title 
Area under the plasma concentrationcurve from time zero to the time of last quantifiable analyte concentration (AUClast) 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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 


End point title 
Area under the plasma concentrationcurve within a dosing interval (AUCτ) 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.


End point type 
Secondary


End point timeframe 
Day 84 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 title 
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 
63


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Slope  
Point estimate 
0.555


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.402  
upper limit 
0.709  
Variability estimate 
Standard error of the mean


Dispersion value 
0.092



End point title 
Average plasma concentration during a dosing interval at steady state (Css,avg) 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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 


End point title 
Dose normalised Css,max (Css,max/D) 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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 


End point title 
Dose normalised AUCτ (AUCτ/D) 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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 


End point title 
Percentage Fluctuation index within a dosing interval 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 (predose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h postdose)




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 


End point title 
Change from baseline of area under the plasma cortisol concentrationtime curve from zero to 24 hours after dosing (AUEC024), 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 logscale as the response, treatment as a fixed effect, and logtransformed baseline value as a covariate.


End point type 
Secondary


End point timeframe 
Day 84 (at 0 [predose], 2, 4, 6, 8, 10, 12, 16, 20, 22 and 24 hours relative to IP administration)




Statistical analysis title 
Statistical Analysis 1  
Comparison groups 
AZD7594 50 μg v Placebo to AZD7594


Number of subjects included in analysis 
33


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.909  
Method 
ANCOVA  
Parameter type 
geometric LSMean ratio  
Point estimate 
1.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.851  
upper limit 
1.199  
Statistical analysis title 
Statistical Analysis 2  
Comparison groups 
AZD7594 90 μg v Placebo to AZD7594


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.218  
Method 
ANCOVA  
Parameter type 
geometric LSMean ratio  
Point estimate 
1.118


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.935  
upper limit 
1.336  
Statistical analysis title 
Statistical Analysis 3  
Comparison groups 
AZD7594 180 μg v Placebo to AZD7594


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.181  
Method 
ANCOVA  
Parameter type 
geometric LSMean ratio  
Point estimate 
1.129


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.944  
upper limit 
1.349  
Statistical analysis title 
Statistical Analysis 4  
Comparison groups 
AZD7594 360 μg v Placebo to AZD7594


Number of subjects included in analysis 
31


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.859  
Method 
ANCOVA  
Parameter type 
geometric LSMean ratio  
Point estimate 
0.984


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.825  
upper limit 
1.174  
Statistical analysis title 
Statistical Analysis 5  
Comparison groups 
AZD7594 720 μg v Placebo to AZD7594


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.285  
Method 
ANCOVA  
Parameter type 
geometric LSMean ratio  
Point estimate 
0.916


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.78  
upper limit 
1.077  
Statistical analysis title 
Statistical Analysis 6  
Comparison groups 
Placebo to AZD7594 v Fluticasone furoate


Number of subjects included in analysis 
31


Analysis specification 
Prespecified


Analysis type 
superiority ^{[42]}  
Pvalue 
= 0.923  
Method 
ANCOVA  
Parameter type 
geometric LSMean ratio  
Point estimate 
0.991


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.831  
upper limit 
1.182  
Notes [42]  The Statistical analysis is done to show the superiority of Fluticasone furoate over Placebo 


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 followup period (7 to 10 days after visit 7)




No statistical analyses for this end point 


Adverse events information


Timeframe for reporting adverse events 
From Screening to followup period (7to 10 days after visit 7)


Assessment type 
Nonsystematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
22.0


Reporting groups


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.  


Frequency threshold for reporting nonserious adverse events: 5%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

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. nonUS sites. Removal of interim futility analysis. Specification of inclusion criterion #7 (prebronchodilator 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 Runin 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 preSABA value at Visit 2, instead of prebronchodilator 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 semilogarithmic 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 concentrationtime data as part of the PK analysis. Clarification of the definition of ACQ5 responder. 

Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
None reported 