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Clinical Trial Results:
A randomized, double-blind, multiple dosing (14 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.

Summary
EudraCT number	2014-005306-37
Trial protocol	DE BG
Global end of trial date	08 Feb 2016

Results information
Results version number	v1(current)
This version publication date	19 Feb 2017
First version publication date	19 Feb 2017
Other versions

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

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Trial information

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Sponsor protocol code

D3741C00003

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

AstraZeneca AB

Sponsor organisation address

Forskargatan 18,, Södertälje, Sweden, 15185

Public contact

Information Centre, AstraZeneca AB, Information Centre, AstraZeneca AB, +1 800 2369933, information.centre@astrazeneca.com

Scientific contact

Global Clinical Leader, Information Centre, AstraZeneca AB, ClinicalTrialTransparency@astrazeneca.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

08 Feb 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

08 Feb 2016

Global end of trial reached?

Yes

Global end of trial date

08 Feb 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective was to investigate the efficacy of AZD7594 as measured by change in trough forced expiratory volume in 1 sec (FEV1) from baseline, as compared to placebo.

Protection of trial subjects

This study was designed and monitored in accordance with with the ethical principles of Good Clinical Practice (GCP) guidelines of the International Conference on Harmonization (ICH) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki (1996). The study was carried out in keeping with local legal requirements as well. The patients were informed of the nature, significance, implications, and risks of the research study. Informed consent was recorded in writing, dated, and signed by the patients before the start of the study, as evidence to indicate that their informed consent was given freely. This consent form was dated and retained by the Investigator as part of the study records. No study-related procedure was performed prior to obtaining informed consent from the patient. The terms of the consent and when it was obtained was also documented in the electronic case report form (eCRF). Informed consent was obtained in line with the Declaration of Helsinki (1996), the current requirements of GCP (Committee for Proprietary Medicinal Products/ICH/135/95), and local regulation – whichever afforded the greatest patient protection. If a protocol amendment was required, the informed consent form (ICF) was revised to reflect the changes to the protocol. If the ICF was revised, it was reviewed and approved by the appropriate independent ethics committee (IEC), and signed by all patients subsequently enrolled in the study as well as those currently enrolled in the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Jun 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 50

Country: Number of subjects enrolled

Bulgaria: 4

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted in Germany (9 centers) & Bulgaria (1 center).110 participants were enrolled (signed informed consent). A total of 54 participants with mild to moderate asthma were randomized after screening, and received study treatment (AZD7594 or placebo) given over 3 Treatment Periods in an incomplete block crossover design.

Screening details

The study consisted of a 2-part run-in period, 3 treatment periods separated by intervening wash-out periods, and a final period of safety follow-up .

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

Blinding implementation details

The study blind was to be broken only in the case of a medical emergency, where knowledge of the IP received could affect the choice of treatment, and in case of a regulatory requirement (eg, for a serious adverse event [SAE] or death).

Are arms mutually exclusive

Yes

Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg )

Arm description

Placebo once daily for 14 days in Period 1, 58 μg AZD7594 once daily for 14 days in Period 2 and 250 μg AZD7594 once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

Placebo once daily for 14 days in Period 1, AZD7594 58 μg once daily for 14 days in Period 2 and AZD7594 250 μg once daily for 14 days in Period 3

Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg)

Arm description

Placebo once daily for 14 days in Period 1, 250 μg AZD7594 once daily for 14 days in Period 2 and 800 μg AZD7594 once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

Placebo once daily for 14 days in Period 1, AZD7594 250 μg once daily for 14 days in Period 2 and AZD7594 800 μg once daily for 14 days in Period 3

Sequence 3 (Placebo + AZD7594 800 μg + AZD7594 58 μg )

Arm description

Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

Placebo once daily for 14 days in Period 1, AZD7594 800 μg once daily for 14 days in Period 2 and AZD7594 58 μg once daily for 14 days in Period 3

Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg)

Arm description

58 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 μg AZD7594 once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

AZD7594 58 μg once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and AZD7594 800 μg once daily for 14 days in Period 3

Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo)

Arm description

58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

AZD7594 58 μg once daily for 14 days in Period 1, AZD7594 800 μg once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg)

Arm description

250 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 μg AZD7594 once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

AZD7594 250 μg once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and AZD7594 58 μg once daily for 14 days in Period 3

Sequence 7 ( AZD7594 250 μg + AZD7594 58 μg + Placebo)

Arm description

250 μg AZD7594 once daily for 14 days in Period 1, 58 μg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

AZD7594 250 μg once daily for 14 days in Period 1, AZD7594 58 μg once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Sequence 8 ( AZD7594 800 μg + Placebo + AZD7594 250 μg)

Arm description

800 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 μg AZD7594 once daily for 14 days

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

AZD7594 800 μg once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and AZD7594 250 μg once daily for 14 days

Sequence 9 ( AZD7594 800 μg + AZD7594 250 μg + Placebo)

Arm description

800 μg AZD7594 once daily for 14 days in Period 1, 250 μg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Arm type

Experimental

Investigational medicinal product name

AZD7594

Investigational medicinal product code

AZD7594

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

AZD7594 800 μg once daily for 14 days in Period 1, AZD7594 250 μg once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Number of subjects in period 1	Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg )	Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg)	Sequence 3 (Placebo + AZD7594 800 μg + AZD7594 58 μg )	Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg)	Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo)	Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg)	Sequence 7 ( AZD7594 250 μg + AZD7594 58 μg + Placebo)	Sequence 8 ( AZD7594 800 μg + Placebo + AZD7594 250 μg)	Sequence 9 ( AZD7594 800 μg + AZD7594 250 μg + Placebo)
Started	6	6	6	7	6	5	6	5	7
Completed	6	6	4	6	5	5	6	4	6
Not completed	0	0	2	1	1	0	0	1	1
Adverse event, non-fatal	-	-	1	-	-	-	-	-	-
Study-specific withdrawal criteria	-	-	1	1	-	-	-	1	1
Randomization to wrong PK sampling group	-	-	-	-	1	-	-	-	-

Baseline characteristics

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Reporting group title

Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg )

Reporting group description

Placebo once daily for 14 days in Period 1, 58 μg AZD7594 once daily for 14 days in Period 2 and 250 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg)

Reporting group description

Placebo once daily for 14 days in Period 1, 250 μg AZD7594 once daily for 14 days in Period 2 and 800 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 3 (Placebo + AZD7594 800 μg + AZD7594 58 μg )

Reporting group description

Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg)

Reporting group description

58 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo)

Reporting group description

58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Reporting group title

Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg)

Reporting group description

250 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 7 ( AZD7594 250 μg + AZD7594 58 μg + Placebo)

Reporting group description

250 μg AZD7594 once daily for 14 days in Period 1, 58 μg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Reporting group title

Sequence 8 ( AZD7594 800 μg + Placebo + AZD7594 250 μg)

Reporting group description

800 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 μg AZD7594 once daily for 14 days

Reporting group title

Sequence 9 ( AZD7594 800 μg + AZD7594 250 μg + Placebo)

Reporting group description

800 μg AZD7594 once daily for 14 days in Period 1, 250 μg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Reporting group values	Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg )	Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg)	Sequence 3 (Placebo + AZD7594 800 μg + AZD7594 58 μg )	Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg)	Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo)	Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg)	Sequence 7 ( AZD7594 250 μg + AZD7594 58 μg + Placebo)	Sequence 8 ( AZD7594 800 μg + Placebo + AZD7594 250 μg)	Sequence 9 ( AZD7594 800 μg + AZD7594 250 μg + Placebo)	Total
Number of subjects	6	6	6	7	6	5	6	5	7	54
Age categorical
Units: Subjects
18 - 75 years	6	6	6	7	6	5	6	5	7	54
Age Continuous \| Age (years)
Units: years
arithmetic mean (standard deviation)	49 ± 14	50 ± 10	56 ± 10	50 ± 17	49 ± 7	55 ± 9	48 ± 14	55 ± 14	46 ± 13	-
Gender, Male/Female
Units: Participants
Female	1	0	2	0	3	2	0	1	1	10
Male	5	6	4	7	3	3	6	4	6	44

Subject analysis set title

AZD7594

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily

Subject analysis set title

Placebo (PBO)

Subject analysis set type

Full analysis

Subject analysis set description

Placebo for AZD7594 DPI once daily

Subject analysis set title

AZD7594 58 μg

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily - 2 capsules of 29 μg

Subject analysis set title

AZD7594 250 μg

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily - 2 capsules of 125 μg

Subject analysis set title

AZD7594 800 μg

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily - 2 capsules of 400 μg

Subject analysis sets values	AZD7594	Placebo (PBO)	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects	34	52	34	34	34
Age categorical
Units: Subjects
18 - 75 years		52	34	34	34
Age Continuous \| Age (years)
Units: years
arithmetic mean (standard deviation)	±	51 ± 12	51 ± 12	50 ± 12	51 ± 12
Gender, Male/Female
Units: Participants
Female	0	8	8	4	6
Male	0	44	26	30	28

End points

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Reporting group title

Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg )

Reporting group description

Placebo once daily for 14 days in Period 1, 58 μg AZD7594 once daily for 14 days in Period 2 and 250 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg)

Reporting group description

Placebo once daily for 14 days in Period 1, 250 μg AZD7594 once daily for 14 days in Period 2 and 800 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 3 (Placebo + AZD7594 800 μg + AZD7594 58 μg )

Reporting group description

Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg)

Reporting group description

58 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo)

Reporting group description

58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Reporting group title

Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg)

Reporting group description

250 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 μg AZD7594 once daily for 14 days in Period 3

Reporting group title

Sequence 7 ( AZD7594 250 μg + AZD7594 58 μg + Placebo)

Reporting group description

250 μg AZD7594 once daily for 14 days in Period 1, 58 μg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Reporting group title

Sequence 8 ( AZD7594 800 μg + Placebo + AZD7594 250 μg)

Reporting group description

800 μg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 μg AZD7594 once daily for 14 days

Reporting group title

Sequence 9 ( AZD7594 800 μg + AZD7594 250 μg + Placebo)

Reporting group description

800 μg AZD7594 once daily for 14 days in Period 1, 250 μg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Subject analysis set title

AZD7594

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily

Subject analysis set title

Placebo (PBO)

Subject analysis set type

Full analysis

Subject analysis set description

Placebo for AZD7594 DPI once daily

Subject analysis set title

AZD7594 58 μg

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily - 2 capsules of 29 μg

Subject analysis set title

AZD7594 250 μg

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily - 2 capsules of 125 μg

Subject analysis set title

AZD7594 800 μg

Subject analysis set type

Full analysis

Subject analysis set description

AZD7594 DPI once daily - 2 capsules of 400 μg

Primary: Efficacy of AZD7594 by assessment of the change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15

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End point title

Efficacy of AZD7594 by assessment of the change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15

End point description

Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 14) with placebo

End point type

Primary

End point timeframe

On Day 1 (pre-dose) and on Day 15 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	51
Units: Liters
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	0.08639 (-0.0165 to 0.1893)	0.05948 (-0.02453 to 0.1435)
AZD7594 250 μg vs. PBO	0.1355 (0.03283 to 0.2382)	0.05948 (-0.02453 to 0.1435)
AZD7594 800 μg vs. PBO	0.2072 (0.1041 to 0.3104)	0.05948 (-0.02453 to 0.1435)

Statistical analysis 1

Statistical analysis description

AZD7594 58 µg vs. Placebo

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6379

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.02691

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08626

upper limit

0.1401

Variability estimate

Standard error of the mean

Dispersion value

0.05697

Statistical analysis 2

Statistical analysis description

AZD7594 250 µg vs.PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1827

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.07604

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03645

upper limit

0.1885

Variability estimate

Standard error of the mean

Dispersion value

0.05663

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0108

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.1478

Confidence interval

level

95%

sides

2-sided

lower limit

0.03494

upper limit

0.2606

Variability estimate

Standard error of the mean

Dispersion value

0.05679

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8

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End point title

Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8

End point description

The efficacy of AZD7594 will be assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8

End point type

Secondary

End point timeframe

On Day 1 (pre-dose) and on Day 8 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	34	52
Units: Parts per billion (ppb)
least squares mean (confidence interval 95%)
AZD7594 58 µg vs. PBO (n=32 for AZD7594)	-9.153 (-15.08 to -3.23)	-4.296 (-9.046 to 0.4536)
AZD7594 250 µg vs. PBO (n=33 for AZD7594)	-14.71 (-20.56 to -8.862)	-4.296 (-9.046 to 0.4536)
AZD7594 800 µg vs. PBO (n=32 for AZD7594)	-19.04 (-24.99 to -13.1)	-4.296 (-9.046 to 0.4536)

Statistical analysis 1

Statistical analysis description

AZD7594 58 µg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1342

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.857

Confidence interval

level

95%

sides

2-sided

lower limit

-11.24

upper limit

1.528

Variability estimate

Standard error of the mean

Dispersion value

3.214

Statistical analysis 2

Statistical analysis description

AZD7594 250 µg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0016

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-10.41

Confidence interval

level

95%

sides

2-sided

lower limit

-16.75

upper limit

-4.075

Variability estimate

Standard error of the mean

Dispersion value

3.19

Statistical analysis 3

Statistical analysis description

AZD7594 800 µg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-14.75

Confidence interval

level

95%

sides

2-sided

lower limit

-21.18

upper limit

-8.319

Variability estimate

Standard error of the mean

Dispersion value

3.236

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15

End point description

The efficacy of AZD7594 will be assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15

End point type

Secondary

End point timeframe

On Day 1 (pre-dose) and on Day 15 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	34	51
Units: Parts per billion (ppb)
least squares mean (confidence interval 95%)
AZD7594 58 µg vs. PBO (n= 32 for AZD7594)	-14.4 (-22.67 to -6.129)	-0.5488 (-6.723 to 5.626)
AZD7594 250 µg vs. PBO (n= 33 for AZD7594)	-14.81 (-22.96 to -6.657)	-0.5488 (-6.723 to 5.626)
AZD7594 800 µg vs. PBO (n= 32 for AZD7594)	-20.44 (-28.72 to -12.17)	-0.5488 (-6.723 to 5.626)

Statistical analysis 1

Statistical analysis description

AZD7594 58 µg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0084

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-13.85

Confidence interval

level

95%

sides

2-sided

lower limit

-24.06

upper limit

-3.642

Variability estimate

Standard error of the mean

Dispersion value

5.139

Statistical analysis 2

Statistical analysis description

AZD7594 250 µg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0062

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-14.26

Confidence interval

level

95%

sides

2-sided

lower limit

-24.37

upper limit

-4.149

Variability estimate

Standard error of the mean

Dispersion value

5.088

Statistical analysis 3

Statistical analysis description

AZD7594 800 µg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-19.9

Confidence interval

level

95%

sides

2-sided

lower limit

-30.1

upper limit

-9.689

Variability estimate

Standard error of the mean

Dispersion value

5.137

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced expiratory volume in 1 second (FEV1) on Day 8

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline in trough forced expiratory volume in 1 second (FEV1) on Day 8

End point description

The efficacy of AZD7594 will be assessed in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7)

End point type

Secondary

End point timeframe

On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	52
Units: Liters
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	0.1016 (-0.00007 to 0.2033)	0.07112 (-0.00922 to 0.1515)
AZD7594 250 μg vs. PBO	0.08856 (-0.01295 to 0.1901)	0.07112 (-0.00922 to 0.1515)
AZD7594 800 μg vs. PBO	0.2272 (0.1252 to 0.3293)	0.07112 (-0.00922 to 0.1515)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6036

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.03051

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08579

upper limit

0.1468

Variability estimate

Standard error of the mean

Dispersion value

0.05856

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.767

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01744

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09912

upper limit

0.134

Variability estimate

Standard error of the mean

Dispersion value

0.05869

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0093

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.1561

Confidence interval

level

95%

sides

2-sided

lower limit

0.03943

upper limit

0.2728

Variability estimate

Standard error of the mean

Dispersion value

0.05874

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 15

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 15

End point description

The efficacy of AZD7594 will be assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 14)

End point type

Secondary

End point timeframe

On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	51
Units: Liters
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	0.04186 (-0.06673 to 0.1505)	0.07653 (-0.01626 to 0.1693)
AZD7594 250 μg vs. PBO	0.1047 (-0.0036 to 0.2131)	0.07653 (-0.01626 to 0.1693)
AZD7594 800 μg vs. PBO	0.1382 (0.02938 to 0.2471)	0.07653 (-0.01626 to 0.1693)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5207

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.03467

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1415

upper limit

0.07213

Variability estimate

Standard error of the mean

Dispersion value

0.05377

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5983

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.02821

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07778

upper limit

0.1342

Variability estimate

Standard error of the mean

Dispersion value

0.05336

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2538

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06169

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04501

upper limit

0.1684

Variability estimate

Standard error of the mean

Dispersion value

0.05371

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 8

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 8

End point description

The efficacy of AZD7594 will be assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7)

End point type

Secondary

End point timeframe

On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	52
Units: Liters
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	0.06179 (-0.04132 to 0.1649)	0.08441 (0.00163 to 0.1672)
AZD7594 250 μg vs. PBO	0.0841 (-0.01877 to 0.187)	0.08441 (0.00163 to 0.1672)
AZD7594 800 μg vs. PBO	0.1527 (0.04929 to 0.2562)	0.08441 (0.00163 to 0.1672)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6945

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02262

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1367

upper limit

0.09144

Variability estimate

Standard error of the mean

Dispersion value

0.05743

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9957

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.00031

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1146

upper limit

0.114

Variability estimate

Standard error of the mean

Dispersion value

0.05755

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2398

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06831

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04637

upper limit

0.183

Variability estimate

Standard error of the mean

Dispersion value

0.05774

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in morning peak expiratory flow (mPEF) before administration over the treatment period

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline in morning peak expiratory flow (mPEF) before administration over the treatment period

End point description

The efficacy of AZD7594 will be assessed in terms of change from baseline in morning peak expiratory flow (mPEF) before administration of the investigational medicinal product (IMP) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as mPEF with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3).

End point type

Secondary

End point timeframe

Every morning at pre-dose from Day 1 to Day 15

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	52
Units: L/min
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	10.42 (-1.909 to 22.74)	0.08136 (-10.5 to 10.66)
AZD7594 250 μg vs. PBO	5.334 (-6.975 to 17.64)	0.08136 (-10.5 to 10.66)
AZD7594 800 μg vs. PBO	12.6 (0.2402 to 24.96)	0.08136 (-10.5 to 10.66)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0819

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.335

upper limit

22.01

Variability estimate

Standard error of the mean

Dispersion value

5.877

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3741

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.253

Confidence interval

level

95%

sides

2-sided

lower limit

-6.427

upper limit

16.93

Variability estimate

Standard error of the mean

Dispersion value

5.881

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0374

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

12.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.7481

upper limit

24.29

Variability estimate

Standard error of the mean

Dispersion value

5.926

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in evening peak expiratory flow (ePEF) before administration over the treatment period

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline in evening peak expiratory flow (ePEF) before administration over the treatment period

End point description

The efficacy of AZD7594 was assessed in terms of change from baseline in evening peak expiratory flow (ePEF) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as ePEF together with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3).

End point type

Secondary

End point timeframe

Every evening from Day 1 to Day 14 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	51
Units: L/min
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	7.475 (-4.426 to 19.38)	-8.257 (-18.71 to 2.193)
AZD7594 250 μg vs. PBO	6.04 (-5.839 to 17.92)	-8.257 (-18.71 to 2.193)
AZD7594 800 μg vs. PBO	11.65 (-0.2692 to 23.58)	-8.257 (-18.71 to 2.193)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0044

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

15.73

Confidence interval

level

95%

sides

2-sided

lower limit

5.039

upper limit

26.43

Variability estimate

Standard error of the mean

Dispersion value

5.384

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0098

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

14.3

Confidence interval

level

95%

sides

2-sided

lower limit

3.534

upper limit

25.06

Variability estimate

Standard error of the mean

Dispersion value

5.419

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

19.91

Confidence interval

level

95%

sides

2-sided

lower limit

9.068

upper limit

30.75

Variability estimate

Standard error of the mean

Dispersion value

5.459

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in average daily use of rescue salbutamol over the treatment period

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline in average daily use of rescue salbutamol over the treatment period

End point description

The efficacy of AZD7594 will be assessed in terms of change from baseline in average daily use of salbutamol (each morning and evening) in each treatment period

End point type

Secondary

End point timeframe

Every day from Day 1 to Day 15 (from evening of Day 1 to morning of Day 15)

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	51
Units: Number of inhalations
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	-0.6776 (-1.071 to -0.2841)	-0.334 (-0.6733 to 0.00522)
AZD7594 250 μg vs. PBO	-0.8193 (-1.212 to -0.4267)	-0.334 (-0.6733 to 0.00522)
AZD7594 800 μg vs. PBO	-1.137 (-1.531 to -0.7422)	-0.334 (-0.6733 to 0.00522)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0723

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.3435

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7189

upper limit

0.03179

Variability estimate

Standard error of the mean

Dispersion value

0.189

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0124

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.4852

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8631

upper limit

-0.1073

Variability estimate

Standard error of the mean

Dispersion value

0.1903

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.8026

Confidence interval

level

95%

sides

2-sided

lower limit

-1.183

upper limit

-0.4224

Variability estimate

Standard error of the mean

Dispersion value

0.1914

Secondary: Efficacy of AZD7594 by assessment of the change from baseline to Day 15 in Asthma Control Questionnaire-5

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline to Day 15 in Asthma Control Questionnaire-5

End point description

The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Each question was scored on a scale of 0 to 6, where a lower score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions (ACQ-5 score = Sum of 5 scores/5).

End point type

Secondary

End point timeframe

At baseline and on Day 15 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	52
Units: Unit on a scale
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	-0.2929 (-0.4744 to -0.1113)	0.01428 (-0.1281 to 0.1567)
AZD7594 250 μg vs. PBO	-0.1681 (-0.3496 to 0.01335)	0.01428 (-0.1281 to 0.1567)
AZD7594 800 μg vs. PBO	-0.4158 (-0.5975 to -0.2342)	0.01428 (-0.1281 to 0.1567)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0044

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.3071

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5159

upper limit

-0.09836

Variability estimate

Standard error of the mean

Dispersion value

0.1051

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0883

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.1824

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3927

upper limit

0.02789

Variability estimate

Standard error of the mean

Dispersion value

0.1059

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.4301

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6397

upper limit

-0.2205

Variability estimate

Standard error of the mean

Dispersion value

0.1055

Secondary: Efficacy of AZD7594 by assessment of the change from baseline to Day 8 in Asthma Control Questionnaire-5

Top of page

End point title

Efficacy of AZD7594 by assessment of the change from baseline to Day 8 in Asthma Control Questionnaire-5

End point description

The efficacy of AZD7594 was assessed in terms of change from baseline to Day 8 in Asthma Control Questionnaire-5 in each treatment period. Each question was scored on a scale of 0 to 6, where a lower score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions (ACQ-5 score = Sum of 5 scores/5)

End point type

Secondary

End point timeframe

At baseline and on Day 8 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	52
Units: Unit on a scale
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	-0.2724 (-0.4309 to -0.1138)	-0.1072 (-0.232 to 0.01748)
AZD7594 250 μg vs. PBO	-0.198 (-0.3565 to -0.03952)	-0.1072 (-0.232 to 0.01748)
AZD7594 800 μg vs. PBO	-0.3604 (-0.5191 to -0.2017)	-0.1072 (-0.232 to 0.01748)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0741

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.1651

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3466

upper limit

0.01638

Variability estimate

Standard error of the mean

Dispersion value

0.09139

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3265

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.09079

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2736

upper limit

0.09201

Variability estimate

Standard error of the mean

Dispersion value

0.09204

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.2532

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4354

upper limit

-0.07092

Variability estimate

Standard error of the mean

Dispersion value

0.09176

Secondary: Efficacy of AZD7594 by assessment of night-time awakenings

Top of page

End point title

Efficacy of AZD7594 by assessment of night-time awakenings

End point description

The efficacy of AZD7594 was assessed in terms of change in nighttime awakenings in each treatment period. The patients were asked to answer ‘Yes’ or ‘No’ to the question of "Did your asthma cause you to wake up last night?”. If yes, the number and percentage of days that had a night-time awakening were determined for each of the study periods.

End point type

Secondary

End point timeframe

At baseline and from Day 1 to Day 14 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	52
Units: Number of nighttime awakenings
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	-0.412 (-0.7229 to -0.101)	0.006541 (-0.2509 to 0.264)
AZD7594 250 μg vs. PBO	-0.1729 (-0.4833 to 0.1376)	0.006541 (-0.2509 to 0.264)
AZD7594 800 μg vs. PBO	-0.7595 (-1.071 to -0.4479)	0.006541 (-0.2509 to 0.264)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0116

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.4185

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7414

upper limit

-0.09563

Variability estimate

Standard error of the mean

Dispersion value

0.1626

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2732

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.1794

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5027

upper limit

0.1438

Variability estimate

Standard error of the mean

Dispersion value

0.1628

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.7661

Confidence interval

level

95%

sides

2-sided

lower limit

-1.091

upper limit

-0.4411

Variability estimate

Standard error of the mean

Dispersion value

0.1636

Secondary: Efficacy of AZD7594 by assessment of daily symptom score

Top of page

End point title

Efficacy of AZD7594 by assessment of daily symptom score

End point description

The efficacy of AZD7594 was assessed in terms of change in daily symptom score from baseline to average of treatment period post dose (Day 1-14) in each treatment period. Severity scores for asthma symptoms were recorded twice daily, once in the morning and once in the evening with the scoring system of 0-no asthma symptoms, 1-toleratable asthma symptoms, 2-discomfort asthma symptoms with normal activities (or with sleep) and 3-asthma symptoms with impaired normal activities (or to sleep).

End point type

Secondary

End point timeframe

At baseline and from Day 1 to Day 15 in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	51
Units: Unit on a scale
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	-0.119 (-0.219 to -0.01903)	-0.01229 (-0.09729 to 0.0727)
AZD7594 250 μg vs. PBO	-0.09435 (-0.1941 to 0.00541)	-0.01229 (-0.09729 to 0.0727)
AZD7594 800 μg vs. PBO	-0.215 (-0.3151 to -0.1149)	-0.01229 (-0.09729 to 0.0727)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0349

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.1067

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2057

upper limit

-0.00775

Variability estimate

Standard error of the mean

Dispersion value

0.04982

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1052

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.08205

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1817

upper limit

0.01756

Variability estimate

Standard error of the mean

Dispersion value

0.05015

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.2027

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3028

upper limit

-0.1025

Variability estimate

Standard error of the mean

Dispersion value

0.05044

Secondary: Efficacy of AZD7594 by assessment of asthma control days

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End point title

Efficacy of AZD7594 by assessment of asthma control days

End point description

The efficacy of AZD7594 was assessed in terms of amount of asthma control days in each treatment period. An asthma control day was defined as a day with asthma symptom score = 0, a night with no awakenings due to asthma symptoms and a day with no use of rescue medication. A given calendar day was defined as an asthma control day if it fulfills the criteria for a symptom-free day and for a rescue medication-free day.

End point type

Secondary

End point timeframe

At baseline and from Day 1 to Day 14 post-dose in each period

End point values	AZD7594	Placebo (PBO)
Number of subjects analysed	33	51
Units: Average number of asthma control days
least squares mean (confidence interval 95%)
AZD7594 58 μg vs. PBO	0.9502 (0.3166 to 1.584)	0.2773 (-0.2745 to 0.829)
AZD7594 250 μg vs. PBO	0.7054 (0.07299 to 1.338)	0.2773 (-0.2745 to 0.829)
AZD7594 800 μg vs. PBO	1.219 (0.5843 to 1.853)	0.2773 (-0.2745 to 0.829)

Statistical analysis 1

Statistical analysis description

AZD7594 58 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0247

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.673

Confidence interval

level

95%

sides

2-sided

lower limit

0.08779

upper limit

1.258

Variability estimate

Standard error of the mean

Dispersion value

0.2946

Statistical analysis 2

Statistical analysis description

AZD7594 250 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1521

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.4281

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1607

upper limit

1.017

Variability estimate

Standard error of the mean

Dispersion value

0.2965

Statistical analysis 3

Statistical analysis description

AZD7594 800 μg vs. PBO

Comparison groups

AZD7594 v Placebo (PBO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.9415

Confidence interval

level

95%

sides

2-sided

lower limit

0.3483

upper limit

1.535

Variability estimate

Standard error of the mean

Dispersion value

0.2987

Secondary: Safety of AZD7594 by assessment of adverse events

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End point title

Safety of AZD7594 by assessment of adverse events

End point description

Assessment of safety and tolerability of three dose levels of AZD7594 in participants with mild to moderate asthma. IP referred to investigational product.

End point type

Secondary

End point timeframe

From Screening to Follow-up (these two examinations are up to 165 days apart)

End point values	Placebo (PBO)	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	52	34	34	34
Units: Number
Any AE	17	13	9	12
AE causally related to IMP	3	1	1	2
Any AE with an outcome of death	0	0	0	0
Any SAE (including events with outcome of death)	0	0	0	0
Any AE leading to discontinuation of IMP	1	0	0	0

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of Cmax of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 by assessment of Cmax of AZD7594

End point description

Comparison of Cmax (maximum observed plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

End point type

Secondary

End point timeframe

On Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: pmol/L
geometric mean (geometric coefficient of variation)
Cmax	36.4 ± 32.8	92.02 ± 34.17	169.7 ± 43.21

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of AUC(0-4) of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 by assessment of AUC(0-4) of AZD7594

End point description

Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

End point type

Secondary

End point timeframe

On Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	4	9	8
Units: h×pmol/L
geometric mean (geometric coefficient of variation)
AUC(0-4)	85.02 ± 8.21	188.4 ± 30.58	371.1 ± 31.55

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax,ss of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax,ss of AZD7594

End point description

Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point type

Secondary

End point timeframe

On Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: pmol/L
geometric mean (geometric coefficient of variation)
Cmax,ss	54.97 ± 19.7	158.7 ± 35.01	421.6 ± 37.26

Statistical analysis 1

Statistical analysis description

AZD7594 250 μg versus AZD7594 58 μg

Comparison groups

AZD7594 58 μg v AZD7594 250 μg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANOVA

Parameter type

Ratio Estimate (%)

Point estimate

272.2

Confidence interval

level

90%

sides

2-sided

lower limit

237.43

upper limit

312.05

Statistical analysis 2

Statistical analysis description

AZD7594 800 μg versus AZD7594 58 μg

Comparison groups

AZD7594 58 μg v AZD7594 800 μg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANOVA

Parameter type

Ratio Estimate (%)

Point estimate

676.13

Confidence interval

level

90%

sides

2-sided

lower limit

580.91

upper limit

786.95

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24) of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24) of AZD7594

End point description

Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point type

Secondary

End point timeframe

On Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: h×pmol/L
geometric mean (geometric coefficient of variation)
AUC(0-24)	467.1 ± 17.91	1725 ± 44.33	4894 ± 52.48

Statistical analysis 1

Statistical analysis description

AZD7594 250 μg versus AZD7594 58 μg

Comparison groups

AZD7594 58 μg v AZD7594 250 μg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANOVA

Parameter type

Ratio Estimate (%)

Point estimate

337.82

Confidence interval

level

90%

sides

2-sided

lower limit

290.8

upper limit

392.43

Statistical analysis 2

Statistical analysis description

AZD7594 800 μg versus AZD7594 58 μg

Comparison groups

AZD7594 58 μg v AZD7594 800 μg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANOVA

Parameter type

Ratio Estimate (%)

Point estimate

964.62

Confidence interval

level

90%

sides

2-sided

lower limit

816.13

upper limit

1140.13

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-last) of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-last) of AZD7594

End point description

Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration) of AZD7594 (i.e. in subjects with intensive pharmacokinetic assessments)

End point type

Secondary

End point timeframe

On Day 1 and Day 14 in each period (in subjects with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: h*pmol/L
geometric mean (geometric coefficient of variation)
Day 1	56.85 ± 45.4	188.5 ± 30.57	371.8 ± 31.63
Day 14	467.3 ± 17.93	1728 ± 44.36	4897 ± 52.48

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of tmax of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 by assessment of tmax of AZD7594

End point description

Comparison of tmax (time to reach maximum plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 hours post-dose)

End point type

Secondary

End point timeframe

On Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: Hour
median (full range (min-max))
tmax	0.25 (0.23 to 0.27)	0.25 (0.25 to 0.5)	0.25 (0.25 to 0.55)

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of tmax,ss of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of tmax,ss of AZD7594

End point description

Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 hours post-dose)

End point type

Secondary

End point timeframe

On Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: Hour
median (full range (min-max))
tmax,ss	0.25 (0.25 to 0.5)	0.25 (0.23 to 0.27)	0.25 (0.25 to 0.98)

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cavg,ss of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cavg,ss of AZD7594

End point description

Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point type

Secondary

End point timeframe

On Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: pmol/L
geometric mean (geometric coefficient of variation)
AZD7594 58 μg (n=9)	19.48 ± 17.93	71.89 ± 44.33	203.9 ± 52.55

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax/D of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax/D of AZD7594

End point description

Comparison of Cmax/D (dose-normalized Cmax) of AZD7594

End point type

Secondary

End point timeframe

On Day 1 in each period

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: pmol/L/μmol
geometric mean (geometric coefficient of variation)
Cmax/D	380.8 ± 32.8	223.4 ± 34.17	128.5 ± 43.21

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24)/D of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24)/D of AZD7594

End point description

Comparison of AUC(0-24)/D (dose-normalized AUC(0-24)) of AZD7594

End point type

Secondary

End point timeframe

On Day 14 in each period

End point values	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	9	8
Units: h×pmol/L/μmol
geometric mean (geometric coefficient of variation)
AUC (0-24)/D	4886 ± 17.91	4188 ± 44.33	3708 ± 52.48

No statistical analyses for this end point

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of steady-state Cmin of AZD7594

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End point title

Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of steady-state Cmin of AZD7594

End point description

Comparison of Cmin (predose concentration) of AZD7594 in each treatment period

End point type

Secondary

End point timeframe

On Day 1 and on Day 14 at pre-dose in each period

End point values	AZD7594 250 μg	AZD7594 800 μg
Number of subjects analysed	9	8
Units: pmol/L
geometric mean (geometric coefficient of variation)
Steady-state Cmin	55.95 ± 51.74	191.6 ± 68.27

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Screening to Follow-up (these two examinations are up to 165 days apart)

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.1.

Reporting group title

Placebo (PBO)

Reporting group description

Placebo for AZD7594 DPI once daily

Reporting group title

AZD7594 58 μg

Reporting group description

AZD7594 DPI once daily - 2 capsules of 29 μg

Reporting group title

AZD7594 250 μg

Reporting group description

AZD7594 DPI once daily - 2 capsules of 125 μg

Reporting group title

AZD7594 800 μg

Reporting group description

AZD7594 DPI once daily - 2 capsules of 400 μg

Serious adverse events	Placebo (PBO)	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo (PBO)	AZD7594 58 μg	AZD7594 250 μg	AZD7594 800 μg
Total subjects affected by non serious adverse events
subjects affected / exposed	17 / 52 (32.69%)	13 / 34 (38.24%)	9 / 34 (26.47%)	12 / 34 (35.29%)
Investigations
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)
occurrences all number	0	0	0	1
Hepatic enzyme increased
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)
occurrences all number	1	0	1	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	3 / 34 (8.82%)	2 / 34 (5.88%)
occurrences all number	0	0	3	2
Migraine
subjects affected / exposed	0 / 52 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	1 / 34 (2.94%)
occurrences all number	0	1	0	1
Blood and lymphatic system disorders
Anaemia vitamin B12 deficiency
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Eye disorders
Eye irritation
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	3 / 34 (8.82%)
occurrences all number	0	0	0	3
Abdominal discomfort
subjects affected / exposed	0 / 52 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	0	1	0	0
Dental caries
subjects affected / exposed	0 / 52 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	0	1	0	0
Abdominal pain upper
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Gingival bleeding
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Toothache
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Vomiting
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 52 (1.92%)	2 / 34 (5.88%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	2	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 52 (0.00%)	1 / 34 (2.94%)	1 / 34 (2.94%)	0 / 34 (0.00%)
occurrences all number	0	1	1	0
Asthma
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)
occurrences all number	1	0	1	0
Epistaxis
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)
occurrences all number	0	0	0	1
Respiratory distress
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)
occurrences all number	0	0	0	1
Sputum increased
subjects affected / exposed	1 / 52 (1.92%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	1	0	0
Dyspnoea
subjects affected / exposed	2 / 52 (3.85%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	2	0	0	0
Nasal inflammation
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Productive cough
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Hepatobiliary disorders
Hepatosplenomegaly
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)
occurrences all number	0	0	0	1
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 52 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	0	1	0	0
Eczema
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 52 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	0	1	0	0
Back pain
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)
occurrences all number	0	0	0	1
Musculoskeletal pain
subjects affected / exposed	0 / 52 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	0	1	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	8 / 52 (15.38%)	4 / 34 (11.76%)	2 / 34 (5.88%)	4 / 34 (11.76%)
occurrences all number	8	4	2	4
Gastroenteritis
subjects affected / exposed	0 / 52 (0.00%)	3 / 34 (8.82%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	0	3	0	0
Gastrointestinal infection
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)
occurrences all number	0	0	1	0
Hordeolum
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)
occurrences all number	0	0	1	0
Rhinitis
subjects affected / exposed	0 / 52 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)
occurrences all number	0	0	1	0
Sinusitis
subjects affected / exposed	1 / 52 (1.92%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)
occurrences all number	1	0	0	0

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Were there any global substantial amendments to the protocol? Yes

26 Jun 2015

Changes are made in the following: Number of study centers, inclusion criteria included reversibility to salbutamol testing in spirometry and a repeat Visit 1 in case reversibility test was negative., exclusion criteria of hypersensitivity to the active substance or to any of the excipients of the Run-in medication, budesonide , thyroid function test (safety laboratory assessments schedule), run-in part 1 (length of budesonide treatment), duration of run-in period (parts 1 & 2) and total study duration for each individual patient

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A randomized, double-blind, multiple dosing (14 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Efficacy of AZD7594 by assessment of the change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15

Primary: Efficacy of AZD7594 by assessment of the change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced expiratory volume in 1 second (FEV1) on Day 8

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced expiratory volume in 1 second (FEV1) on Day 8

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 15

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 15

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 8

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in trough forced vital capacity (FVC) on Day 8

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in morning peak expiratory flow (mPEF) before administration over the treatment period

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in morning peak expiratory flow (mPEF) before administration over the treatment period

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in evening peak expiratory flow (ePEF) before administration over the treatment period

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in evening peak expiratory flow (ePEF) before administration over the treatment period

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in average daily use of rescue salbutamol over the treatment period

Secondary: Efficacy of AZD7594 by assessment of the change from baseline in average daily use of rescue salbutamol over the treatment period

Secondary: Efficacy of AZD7594 by assessment of the change from baseline to Day 15 in Asthma Control Questionnaire-5

Secondary: Efficacy of AZD7594 by assessment of the change from baseline to Day 15 in Asthma Control Questionnaire-5

Secondary: Efficacy of AZD7594 by assessment of the change from baseline to Day 8 in Asthma Control Questionnaire-5

Secondary: Efficacy of AZD7594 by assessment of the change from baseline to Day 8 in Asthma Control Questionnaire-5

Secondary: Efficacy of AZD7594 by assessment of night-time awakenings

Secondary: Efficacy of AZD7594 by assessment of night-time awakenings

Secondary: Efficacy of AZD7594 by assessment of daily symptom score

Secondary: Efficacy of AZD7594 by assessment of daily symptom score

Secondary: Efficacy of AZD7594 by assessment of asthma control days

Secondary: Efficacy of AZD7594 by assessment of asthma control days

Secondary: Safety of AZD7594 by assessment of adverse events

Secondary: Safety of AZD7594 by assessment of adverse events

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of Cmax of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of Cmax of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of AUC(0-4) of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of AUC(0-4) of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax,ss of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax,ss of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24) of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24) of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-last) of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-last) of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of tmax of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 by assessment of tmax of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of tmax,ss of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of tmax,ss of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cavg,ss of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cavg,ss of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax/D of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of Cmax/D of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24)/D of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of AUC(0-24)/D of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of steady-state Cmin of AZD7594

Secondary: Rate and extent of absorption of three dose levels of AZD7594 following multiple dose administration by assessment of steady-state Cmin of AZD7594

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A randomized, double-blind, multiple dosing (14 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.