Single dose study to assess efficacy, safety and tolerability of LAS100977 in asthmatic patients.

Study identifier:M/100977/202

ClinicalTrials.gov identifier:NCT01425801

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase IIa, randomised, single dose, double-blind, double-dummy, 6 way complete cross-over, placebo controlled clinical trial to assess the efficacy, safety and tolerability of 4 doses of LAS100977 QD compared to placebo and an active comparator in patients with persistent asthma.

Medical condition

asthma

Phase

Phase 2

Healthy volunteers

Study drug

LAS100977 0.313 μg, LAS100977 0.625 μg, LAS100977 1.25 μg, LAS100977 2.5 μg, Salbutamol 400 μg, Salbutamol placebo, LAS100977 placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 01 Aug 2011

Primary Completion Date: 01 Feb 2012

Study Completion Date: 01 Feb 2012

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2018 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Almirall Investigational Sites#5

Wiesbaden, Germany, 65187

Location

Almirall Investigational Sites#1

Berlin, Germany, 14057

Location

Almirall Investigational Sites#2

Grosshansdorf, Germany, 22927

Location

Almirall Investigational Sites#3

Frankfurt, Germany, 60596

Location

Almirall Investigational Sites#4

Berlin, Germany, 14050

Location

Almirall Investigational Sites#6

Berlin, Germany, 10117

Location

Almirall Investigational Sites#8

Hamburg, Germany, 20249

Location

Almirall Investigational Sites#1

Manchester, United Kingdom, M3 9QZ

Arms	Assigned Interventions
Experimental: LAS100977 0.625 μg Single-dose LAS100977 0.625 μg, during double-blind treatment period	Drug: LAS100977 0.625 μg Dry powder inhalation, once-daily, single-dose Drug: Salbutamol placebo Pressurized inhalation, once-daily
Experimental: LAS100977 1.25 μg Single-dose LAS100977 1.25 μg, during double-blind treatment period	Drug: LAS100977 1.25 μg Dry powder inhalation, once-daily, single-dose Drug: Salbutamol placebo Pressurized inhalation, once-daily
Experimental: LAS100977 2.5 μg Single-dose LAS100977 2.5 μg, during double-blind treatment period	Drug: LAS100977 2.5 μg Dry powder inhalation, once-daily, single-dose Drug: Salbutamol placebo Pressurized inhalation, once-daily
Active Comparator: Salbutamol Single-dose salbutamol 400 μg, during double-blind treatment period	Drug: Salbutamol 400 μg Pressurized inhalation suspension, once-daily, single-dose Drug: LAS100977 placebo Dry powder inhalation, once-daily
Placebo Comparator: Placebo Placebo to LAS100977, and placebo to salbutamol	Drug: Salbutamol placebo Pressurized inhalation, once-daily Drug: LAS100977 placebo Dry powder inhalation, once-daily
Experimental: LAS100977 0.313 μg Single-dose LAS100977 0.313 μg, during double-blind treatment period	Drug: LAS100977 0.313 μg Dry powder inhalation, once-daily, single-dose Drug: Salbutamol placebo Pressurized inhalation, once-daily

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted in 10 sites in Germany and United Kingdom, 9 of which randomized patients

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening took place 12-16 days before randomization. After screening, eligible patients entered a run-in period to assess clinical stability. A total of 115 patients were screened; 62 patients were assessed as eligible and randomized; 53 were not randomized due to screening failure (primarily non-fulfillment of inclusion/exclusion criteria)

Reporting Groups

	Description
Sequence A	Salbutamol 400 μg - LAS100977 0.313 μg - Placebo - LAS100977 0.625 μg - LAS100977 2.5 μg - LAS100977 1.25 μg
Sequence B	LAS100977 0.313 μg - LAS100977 0.625 μg - Salbutamol 400 μg - LAS100977 1.25 μg - Placebo - LAS100977 2.5 μg
Sequence C	LAS100977 0.625 μg - LAS100977 1.25 μg - LAS100977 0.313 μg - LAS100977 2.5 μg - Salbutamol 400 μg - Placebo
Sequence D	LAS100977 1.25 μg - LAS100977 2.5 μg - LAS100977 0.625 μg - Placebo - LAS100977 0.313 μg - Salbutamol 400 μg
Sequence E	LAS100977 2.5 μg - Placebo - LAS100977 1.25 μg - Salbutamol 400 μg - LAS100977 0.625 μg - LAS100977 0.313 μg
Sequence F	Placebo - Salbutamol 400 μg - LAS100977 2.5 μg - LAS100977 0.313 μg - LAS100977 1.25 μg - LAS100977 0.625 μg

Participant Flow for 6 periods

Period 1: Period 1

	Sequence A	Sequence B	Sequence C	Sequence D	Sequence E	Sequence F
STARTED	9	9	9	12	13	10
COMPLETED	9	9	9	12	12	10
NOT COMPLETED	0	0	0	0	1	0
Withdrawal by Subject	0	0	0	0	1	0

Period 2: Period 2

	Sequence A	Sequence B	Sequence C	Sequence D	Sequence E	Sequence F
STARTED	9	9	9	12	12	10
COMPLETED	9	9	9	12	11	10
NOT COMPLETED	0	0	0	0	1	0
Withdrawal by Subject	0	0	0	0	1	0

Period 3: Period 3

	Sequence A	Sequence B	Sequence C	Sequence D	Sequence E	Sequence F
STARTED	9	9	9	12	11	10
COMPLETED	9	9	8	12	11	10
NOT COMPLETED	0	0	1	0	0	0
Stability criteria not fullfilled	0	0	1	0	0	0

Period 4: Period 4

	Sequence A	Sequence B	Sequence C	Sequence D	Sequence E	Sequence F
STARTED	9	9	8	12	11	10
COMPLETED	9	9	7	12	11	10
NOT COMPLETED	0	0	1	0	0	0
Not able to maintain visit schedule	0	0	1	0	0	0

Period 5: Period 5

	Sequence A	Sequence B	Sequence C	Sequence D	Sequence E	Sequence F
STARTED	9	9	7	12	11	10
COMPLETED	9	9	7	12	11	10
NOT COMPLETED	0	0	0	0	0	0

Period 6: Period 6

	Sequence A	Sequence B	Sequence C	Sequence D	Sequence E	Sequence F
STARTED	9	9	7	12	11	10
COMPLETED	9	9	7	12	11	10
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Overall population	Safety population defined as all patients who were randomized and received at least one dose of investigational medicinal product

Baseline Measures

	Overall population
Number of Participants [units: Participants]	62
Age Continuous [units: Years] Mean ± Standard Deviation	40.9 ± 11.2
Gender, Male/Female [units: ]
Female	22
Male	40

Outcome Measures

1. Primary Outcome Measure: Change from baseline in peak forced expiratory volume in one second (FEV1) [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]

Measure Type	Primary
Measure Name	Change from baseline in peak forced expiratory volume in one second (FEV1)
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Change from baseline in peak forced expiratory volume in one second (FEV1) [units: Liters] Least Squares Mean (Standard Error)	0.202 (0.045)	0.477 (0.045)	0.524 (0.045)	0.573 (0.045)	0.608 (0.045)	0.555 (0.045)

Statistical Analysis 1 for Change from baseline in peak forced expiratory volume in one second (FEV1)

Groups^[1]	Placebo, LAS100977 2.5 μg
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Other^[5]	0.405
Standard Error of the mean	± 0.027
95% Confidence Interval	( 0.353 to 0.458 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Sequence, treatment and period as fixed effect factors, patient within sequence as random effect and baseline peak FEV1 at each period as a covariate
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline in peak forced expiratory volume in one second (FEV1)

Groups^[1]	Placebo, LAS100977 1.25 μg
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Other^[5]	0.371
Standard Error of the mean	± 0.027
95% Confidence Interval	( 0.318 to 0.424 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Sequence, treatment and period as fixed effect factors, patient within sequence as random effect and baseline peak FEV1 at each period as a covariate
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change from baseline in peak forced expiratory volume in one second (FEV1)

Groups^[1]	Placebo, LAS100977 0.625 μg
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Other^[5]	0.322
Standard Error of the mean	± 0.027
95% Confidence Interval	( 0.269 to 0.375 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Sequence, treatment and period as fixed effect factors, patient within sequence as random effect and baseline peak FEV1 at each period as a covariate
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Change from baseline in peak forced expiratory volume in one second (FEV1)

Groups^[1]	Placebo, LAS100977 0.313 μg
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Other^[5]	0.274
Standard Error of the mean	± 0.027
95% Confidence Interval	( 0.221 to 0.327 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Sequence, treatment and period as fixed effect factors, patient within sequence as random effect and baseline peak FEV1 at each period as a covariate
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Percentage change from baseline in peak forced expiratory volume in one second (FEV1) [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in peak forced expiratory volume in one second (FEV1)
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Percentage change from baseline in peak forced expiratory volume in one second (FEV1) [units: Percent change] Least Squares Mean (Standard Error)	7.555 (1.655)	18.282 (1.651)	20.212 (1.651)	21.809 (1.651)	23.077 (1.650)	21.374 (1.658)

No statistical analysis provided for Percentage change from baseline in peak forced expiratory volume in one second (FEV1)

3. Secondary Outcome Measure: Peak forced expiratory volume in one second (FEV1) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]

Measure Type	Secondary
Measure Name	Peak forced expiratory volume in one second (FEV1)
Measure Description	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time Frame	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Peak forced expiratory volume in one second (FEV1) [units: Liters] Least Squares Mean (Standard Error)	2.855 (0.045)	3.129 (0.045)	3.177 (0.045)	3.225 (0.045)	3.260 (0.045)	3.207 (0.045)

No statistical analysis provided for Peak forced expiratory volume in one second (FEV1)

4. Secondary Outcome Measure: Time to peak forced expiratory volume in one second (FEV1) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]

Measure Type	Secondary
Measure Name	Time to peak forced expiratory volume in one second (FEV1)
Measure Description	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time Frame	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Time to peak forced expiratory volume in one second (FEV1) [units: Hours] Mean (Standard Deviation)	2.3 (1.3)	2.6 (1.3)	3.0 (1.1)	3.1 (0.9)	3.0 (1.1)	1.1 (0.8)

No statistical analysis provided for Time to peak forced expiratory volume in one second (FEV1)

5. Secondary Outcome Measure: Change from baseline to trough forced expiratory volume in one second (FEV1) [ Time Frame: Baseline and +23 h and +24 h post-dose ]

Measure Type	Secondary
Measure Name	Change from baseline to trough forced expiratory volume in one second (FEV1)
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	Baseline and +23 h and +24 h post-dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	58	60	60	60	60	58
Change from baseline to trough forced expiratory volume in one second (FEV1) [units: Liters] Least Squares Mean (Standard Error)	-0.054 (0.039)	0.166 (0.039)	0.205 (0.039)	0.278 (0.039)	0.346 (0.039)	-0.076 (0.039)

No statistical analysis provided for Change from baseline to trough forced expiratory volume in one second (FEV1)

6. Secondary Outcome Measure: Change from baseline in normalized forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-24h at Day 1 [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h ]

Measure Type	Secondary
Measure Name	Change from baseline in normalized forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-24h at Day 1
Measure Description	FEV1 was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	57	59	60	60	59	53
Change from baseline in normalized forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-24h at Day 1 [units: Liters] Least Squares Mean (Standard Error)	0.007 (0.039)	0.282 (0.039)	0.321 (0.038)	0.390 (0.038)	0.446 (0.039)	0.100 (0.039)

No statistical analysis provided for Change from baseline in normalized forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-24h at Day 1

7. Secondary Outcome Measure: Absolute values of forced expiratory volume (FEV1) at each timepoint [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h ]

Measure Type	Secondary
Measure Name	Absolute values of forced expiratory volume (FEV1) at each timepoint
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Absolute values of forced expiratory volume (FEV1) at each timepoint [units: Liters] Least Squares Mean (Standard Error)
0.25 hr	2.696 (0.030)	2.863 (0.030)	2.886 (0.030)	2.934 (0.030)	3.007 (0.030)	3.106 (0.030)
1 hr	2.719 (0.037)	3.000 (0.037)	3.025 (0.037)	3.098 (0.037)	3.133 (0.037)	3.147 (0.037)
2 hr	2.746 (0.039)	3.034 (0.038)	3.081 (0.038)	3.136 (0.038)	3.188 (0.039)	3.123 (0.039)
3 hr	2.771 (0.041)	3.069 (0.041)	3.102 (0.041)	3.190 (0.041)	3.196 (0.041)	3.040 (0.041)
4 hr	2.774 (0.044)	3.058 (0.044)	3.124 (0.044)	3.167 (0.044)	3.211 (0.044)	2.937 (0.044)
6 hr	2.722 (0.038)	3.008 (0.038)	3.087 (0.038)	3.157 (0.038)	3.194 (0.038)	2.812 (0.038)
8 hr	2.715 (0.040)	3.033 (0.039)	3.062 (0.039)	3.139 (0.039)	3.180 (0.039)	2.772 (0.039)
12 hr	2.659 (0.044)	2.943 (0.043)	2.980 (0.043)	3.035 (0.043)	3.111 (0.043)	2.669 (0.044)
14 hr	2.597 (0.042)	2.903 (0.041)	2.941 (0.041)	3.018 (0.041)	3.094 (0.042)	2.683 (0.043)
23 hr	2.588 (0.040)	2.804 (0.039)	2.836 (0.040)	2.923 (0.040)	2.985 (0.040)	2.562 (0.040)
24 hr	2.618 (0.040)	2.840 (0.039)	2.890 (0.040)	2.948 (0.040)	3.019 (0.040)	2.605 (0.040)
36 hr	2.689 (0.042)	2.823 (0.041)	2.798 (0.041)	2.892 (0.041)	2.929 (0.041)	2.690 (0.041)
0.5 hr	2.723 (0.034)	2.956 (0.033)	2.972 (0.033)	3.033 (0.033)	3.089 (0.033)	3.142 (0.034)

No statistical analysis provided for Absolute values of forced expiratory volume (FEV1) at each timepoint

8. Secondary Outcome Measure: Change from baseline in forced expiratory volume (FEV1) at each timepoint [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h ]

Measure Type	Secondary
Measure Name	Change from baseline in forced expiratory volume (FEV1) at each timepoint
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Change from baseline in forced expiratory volume (FEV1) at each timepoint [units: Liters] Least Squares Mean (Standard Error)
0.25 hr	0.048 (0.030)	0.214 (0.030)	0.237 (0.030)	0.285 (0.030)	0.358 (0.030)	0.457 (0.030)
0.5 hr	0.071 (0.034)	0.304 (0.033)	0.319 (0.033)	0.381 (0.033)	0.437 (0.033)	0.490 (0.034)
1 hr	0.067 (0.037)	0.348 (0.037)	0.373 (0.037)	0.446 (0.037)	0.481 (0.037)	0.495 (0.037)
2 hr	0.094 (0.039)	0.382 (0.038)	0.429 (0.038)	0.484 (0.038)	0.536 (0.039)	0.471 (0.039)
3 hr	0.119 (0.041)	0.416 (0.041)	0.450 (0.041)	0.537 (0.041)	0.543 (0.041)	0.388 (0.041)
4 hr	0.121 (0.044)	0.406 (0.044)	0.471 (0.044)	0.515 (0.044)	0.558 (0.044)	0.284 (0.044)
6 hr	0.067 (0.038)	0.353 (0.038)	0.432 (0.038)	0.501 (0.038)	0.539 (0.038)	0.157 (0.038)
8 hr	0.056 (0.040)	0.374 (0.039)	0.403 (0.039)	0.480 (0.039)	0.521 (0.039)	0.113 (0.039)
12 hr	0.005 (0.044)	0.288 (0.043)	0.326 (0.043)	0.380 (0.043)	0.456 (0.043)	0.014 (0.044)
14 hr	-0.053 (0.042)	0.253 (0.041)	0.291 (0.041)	0.367 (0.041)	0.443 (0.042)	0.032 (0.043)
23 hr	-0.067 (0.040)	0.148 (0.039)	0.181 (0.040)	0.268 (0.040)	0.330 (0.040)	-0.093 (0.040)
24 hr	-0.040 (0.040)	0.183 (0.039)	0.233 (0.040)	0.291 (0.040)	0.362 (0.040)	-0.052 (0.040)
36 hr	0.035 (0.042)	0.169 (0.041)	0.144 (0.041)	0.238 (0.041)	0.275 (0.041)	0.036 (0.041)

No statistical analysis provided for Change from baseline in forced expiratory volume (FEV1) at each timepoint

9. Secondary Outcome Measure: Percentage change from baseline in forced expiratory volume (FEV1) at each timepoint [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h ]

Measure Type	Secondary
Measure Name	Percentage change from baseline in forced expiratory volume (FEV1) at each timepoint
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Percentage change from baseline in forced expiratory volume (FEV1) at each timepoint [units: Percent change] Least Squares Mean (Standard Error)
0.25 hr	1.519 (1.090)	8.325 (1.084)	8.846 (1.084)	10.789 (1.084)	13.511 (1.081)	17.744 (1.098)
0.5 hr	2.449 (1.205)	11.757 (1.199)	12.006 (1.199)	14.362 (1.199)	16.715 (1.196)	18.806 (12.209)
1 hr	2.407 (1.356)	13.452 (1.350)	14.307 (1.350)	16.927 (1.350)	18.336 (1.352)	19.085 (1.360)
2 hr	3.520 (1.434)	14.741 (1.427)	16.371 (1.428)	18.509 (1.428)	20.226 (1.430)	17.755 (1.438)
3 hr	4.435 (1.479)	15.965 (1.472)	17.190 (1.472)	20.357 (1.477)	20.550 (1.470)	14.537 (1.484)
4 hr	4.288 (1.596)	15.400 (1.589)	17.960 (1.590)	19.454 (1.590)	21.155 (1.587)	10.608 (1.600)
6 hr	2.682 (1.439)	13.661 (1.424)	16.490 (1.425)	19.080 (1.425)	20.612 (1.421)	5.796 (1.438)
8 hr	2.752 (1.505)	14.118 (1.482)	15.128 (1.482)	18.199 (1.482)	19.733 (1.478)	4.493 (1.497)
12 hr	0.402 (1.627)	10.847 (1.614)	12.388 (1.614)	14.251 (1.614)	17.170 (1.616)	0.997 (1.639)
14 hr	-1.903 (1.559)	9.427 (1.551)	11.008 (1.544)	11.771 (1.544)	16.716 (1.555)	1.892 (1.594)
23 hr	-2.117 (1.464)	5.451 (1.444)	6.955 (1.445)	9.893 (1.445)	12.375 (1.449)	-3.649 (1.464)
24 hr	-0.611 (1.473)	7.084 (1.453)	8.918 (1.461)	10.975 (1.461)	13.716 (1.458)	-1.736 (1.482)
36 hr	1.904 (1.574)	6.396 (1.554)	5.589 (1.555)	8.742 (1.555)	10.370 (1.558)	2.098 (1.572)

No statistical analysis provided for Percentage change from baseline in forced expiratory volume (FEV1) at each timepoint

10. Secondary Outcome Measure: Change from baseline in peak forced vital capacity (FVC) [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]

Measure Type	Secondary
Measure Name	Change from baseline in peak forced vital capacity (FVC)
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Change from baseline in peak forced vital capacity (FVC) [units: Liters] Least Squares Mean (Standard Error)	0.222 (0.034)	0.317 (0.034)	0.329 (0.034)	0.361 (0.034)	0.380 (0.034)	0.361 (0.034)

No statistical analysis provided for Change from baseline in peak forced vital capacity (FVC)

11. Secondary Outcome Measure: Peak forced vital capacity (FVC) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h ]

Measure Type	Secondary
Measure Name	Peak forced vital capacity (FVC)
Measure Description	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Peak forced vital capacity (FVC) [units: Liters] Least Squares Mean (Standard Error)	4.483 (0.034)	4.578 (0.034)	4.590 (0.034)	4.622 (0.034)	4.641 (0.034)	4.622 (0.034)

No statistical analysis provided for Peak forced vital capacity (FVC)

12. Secondary Outcome Measure: Time to peak forced vital capacity (FVC) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h ]

Measure Type	Secondary
Measure Name	Time to peak forced vital capacity (FVC)
Measure Description	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Time to peak forced vital capacity (FVC) [units: Hours] Mean (Standard Deviation)	2.1 (1.4)	1.8 (1.4)	2.3 (1.4)	2.1 (1.2)	2.2 (1.4)	1.5 (1.2)

No statistical analysis provided for Time to peak forced vital capacity (FVC)

13. Secondary Outcome Measure: Change from baseline to trough forced vital capacity (FVC) [ Time Frame: Baseline and +23 h +24 h post-dose ]

Measure Type	Secondary
Measure Name	Change from baseline to trough forced vital capacity (FVC)
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	Baseline and +23 h +24 h post-dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	58	60	60	60	60	58
Change from baseline to trough forced vital capacity (FVC) [units: Liters] Least Squares Mean (Standard Error)	-0.028 (0.035)	0.094 (0.035)	0.050 (0.035)	0.111 (0.035)	0.120 (0.035)	-0.065 (0.035)

No statistical analysis provided for Change from baseline to trough forced vital capacity (FVC)

14. Secondary Outcome Measure: Change from baseline in normalized forced vital capacity (FVC) area under the curve (AUC) [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h ]

Measure Type	Secondary
Measure Name	Change from baseline in normalized forced vital capacity (FVC) area under the curve (AUC)
Measure Description	FVC was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	57	59	60	60	59	53
Change from baseline in normalized forced vital capacity (FVC) area under the curve (AUC) [units: Liters] Least Squares Mean (Standard Error)	0.017 (0.031)	0.135 (0.031)	0.109 (0.030)	0.169 (0.030)	0.192 (0.031)	0.054 (0.031)

No statistical analysis provided for Change from baseline in normalized forced vital capacity (FVC) area under the curve (AUC)

15. Secondary Outcome Measure: Absolute values of forced vital capacity (FVC) at each timepoint [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h ]

Measure Type	Secondary
Measure Name	Absolute values of forced vital capacity (FVC) at each timepoint
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Absolute values of forced vital capacity (FVC) at each timepoint [units: Liters] Least Squares Mean (Standard Error)
0.25h	4.295 (0.030)	4.420 (0.030)	4.368 (0.030)	4.383 (0.030)	4.417 (0.030)	4.471 (0.030)
0.5 hr	4.320 (0.032)	4.458 (0.032)	4.405 (0.032)	4.438 (0.032)	4.443 (0.032)	4.502 (0.032)
1 hr	4.295 (0.034)	4.442 (0.034)	4.429 (0.034)	4.480 (0.034)	4.498 (0.034)	4.502 (0.034)
2 hr	4.321 (0.034)	4.445 (0.034)	4.444 (0.034)	4.495 (0.034)	4.512 (0.034)	4.477 (0.034)
3 hr	4.352 (0.036)	4.462 (0.035)	4.472 (0.035)	4.505 (0.035)	4.505 (0.035)	4.454 (0.036)
4 hr	4.316 (0.035)	4.459 (0.035)	4.462 (0.035)	4.463 (0.035)	4.517 (0.034)	4.398 (0.035)
6 hr	4.322 (0.033)	4.413 (0.033)	1.411 (0.033)	4.464 (0.033)	4.513 (0.033)	4.360 (0.033)
8 hr	4.325 (0.035)	4.456 (0.035)	4.412 (0.035)	4.487 (0.035)	4.499 (0.035)	4.335 (0.035)
12 hr	4.310 (0.036)	4.409 (0.036)	4.349 (0.036)	4.414 (0.036)	4.453 (0.036)	4.277 (0.037)
14 hr	4.235 (0.036)	4.357 (0.036)	4.360 (0.036)	4.436 (0.036)	4.458 (0.036)	4.269 (0.037)
23 hr	4.244 (0.037)	4.366 (0.036)	4.303 (0.036)	4.375 (0.036)	4.367 (0.036)	4.223 (0.037)
24 hr	4.238 (0.038)	4.359 (0.037)	4.335 (0.038)	4.384 (0.038)	4.410 (0.038)	4.193 (0.038)
36 hr	4.252 (0.040)	4.390 (0.039)	4.280 (0.039)	4.352 (0.039)	4.381 (0.039)	4.284 (0.040)

No statistical analysis provided for Absolute values of forced vital capacity (FVC) at each timepoint

16. Secondary Outcome Measure: Change from baseline in forced vital capacity (FVC) at each timepoint [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h ]

Measure Type	Secondary
Measure Name	Change from baseline in forced vital capacity (FVC) at each timepoint
Measure Description	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time Frame	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Measured Values

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Number of Participants Analyzed [units:participants]	59	60	60	60	61	58
Change from baseline in forced vital capacity (FVC) at each timepoint [units: Liters] Least Squares Mean (Standard Error)
0.25 hr	0.038 (0.030)	0.162 (0.030)	0.111 (0.030)	0.125 (0.030)	0.159 (0.030)	0.213 (0.030)
0.5 hr	0.059 (0.032)	0.197 (0.032)	0.144 (0.032)	0.177 (0.032)	0.182 (0.032)	0.241 (0.032)
1 hr	0.034 (0.034)	0.182 (0.034)	0.169 (0.034)	0.219 (0.034)	0.237 (0.034)	0.242 (0.034)
2 hr	0.060 (0.034)	0.184 (0.034)	0.183 (0.034)	0.234 (0.034)	0.252 (0.034)	0.217 (0.034)
3 hr	0.089 (0.036)	0.199 (0.035)	0.209 (0.035)	0.241 (0.035)	0.242 (0.035)	0.191 (0.036)
4 hr	0.055 (0.035)	0.198 (0.035)	0.201 (0.035)	0.202 (0.035)	0.256 (0.034)	0.137 (0.035)
6 hr	0.057 (0.033)	0.149 (0.033)	0.147 (0.033)	0.200 (0.033)	0.249 (0.033)	0.096 (0.033)
8 hr	0.054 (0.035)	0.185 (0.035)	0.141 (0.035)	0.216 (0.035)	0.228 (0.035)	0.064 (0.035)
12 hr	0.042 (0.036)	0.141 (0.036)	0.081 (0.036)	0.146 (0.036)	0.185 (0.036)	0.001 (0.037)
14 hr	-0.027 (0.036)	0.095 (0.036)	0.097 (0.036)	0.173 (0.036)	0.195 (0.036)	0.006 (0.037)
23 hr	-0.022 (0.037)	0.101 (0.036)	0.038 (0.036)	0.110 (0.036)	0.102 (0.036)	-0.043 (0.037)
24 hr	-0.034 (0.038)	0.086 (0.037)	0.063 (0.038)	0.111 (0.038)	0.137 (0.038)	-0.079 (0.038)
36 hr	-0.011 (0.040)	0.128 (0.039)	0.018 (0.039)	0.089 (0.039)	0.118 (0.039)	0.022 (0.040)

No statistical analysis provided for Change from baseline in forced vital capacity (FVC) at each timepoint

Serious Adverse Events

Time Frame	Up to 14 (±2) days after last intake of investigational medicinal product
Additional Description	Safety population defined as all randomized patients who took at least 1 dose of investigational medicinal product The total number of patients in the safety population was 62; due to study drop-out and the crossover study design, not all patients received all treatments

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Serious Adverse Events

	Placebo	LAS100977 0.313 μg	LAS100977 0.625 μg	LAS100977 1.25 μg	LAS100977 2.5 μg	Salbutamol 400 μg
Total, serious adverse events
# participants affected / at risk	0/59 (0.00%)	0/60 (0.00%)	0/60 (0.00%)	0/60 (0.00%)	0/61 (0.00%)	0/62 (0.00%)

Other Adverse Events

Time Frame	Up to 14 (±2) days after last intake of investigational medicinal product
Additional Description	Safety population defined as all randomized patients who took at least 1 dose of investigational medicinal product The total number of patients in the safety population was 62; due to study drop-out and the crossover study design, not all patients received all treatments

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Placebo	Dry powder administered via the Genuair® inhaler or pressurised inhalation suspension administered via Ventolin Evohaler®
LAS100977 0.313 μg	Dry powder administered via the Genuair® inhaler
LAS100977 0.625 μg	Dry powder for inhalation administered via Genuair®
LAS100977 1.25 μg	Dry powder for inhalation administered via Genuair®
LAS100977 2.5 μg	Dry powder for inhalation administered via Genuair®
Salbutamol 400 μg	Pressurised inhalation suspension administered via Ventolin Evohaler®

Other Adverse Events

Placebo

LAS100977 0.313 μg

LAS100977 0.625 μg

LAS100977 1.25 μg

LAS100977 2.5 μg

Salbutamol 400 μg

Total, other (not including serious) adverse events

# participants affected / at risk

8/59 (13.56%)

12/60 (20.00%)

10/60 (16.67%)

12/60 (20.00%)

9/61 (14.75%)

6/62 (9.68%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

7/59 (11.86%)

4/60 (6.67%)

7/60 (11.67%)

8/60 (13.33%)

7/61 (11.48%)

6/62 (9.68%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

1/59 (1.69%)

8/60 (13.33%)

3/60 (5.00%)

4/60 (6.67%)

2/61 (3.28%)

0/62 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 14.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Publication and/or presentation whether complete or partial, of any part of the data or results of this trial will be subject to revision and written agreement between the investigator and sponsor

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Study Director
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Synopsis-M-100977-202
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical

1-877-2409479

information.center@astrazeneca.com

Investigators

Principal Investigator

Carol Astbury

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Almirall Investigational Sites#5

Almirall Investigational Sites#1

Almirall Investigational Sites#2

Almirall Investigational Sites#3

Almirall Investigational Sites#4

Almirall Investigational Sites#6

Almirall Investigational Sites#8

Almirall Investigational Sites#1

Synopsis-M-100977-202

Trial Results Summaries