Single Dose Study to Assess Efficacy and Safety of 4 Doses of LAS100977 in Chronic Obstructive Pulmonary Disease (COPD) Population

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01425814
• Collaborator: (none)
• Enrollment: 87
• Locations: 8
• Arms: 6
• Duration (Months): 7
• Patients Per Site: 10.9
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the pharmacodynamics (bronchodilation) of single doses of inhaled LAS100977 in COPD patients.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: LAS100977; Drug: LAS100977; Drug: LAS100977; Drug: LAS100977; Drug: Reference; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Strengths of LAS100977 QD Compared to Placebo and an Active Comparator in Patients With Stable Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm #2 Single dose, double blind treatment period	Drug: LAS100977; Dry powder inhalation,Once daily, single dose
Experimental: Arm #3 Single dose, double blind treatment period	Drug: LAS100977; Dry powder inhalation,Once daily, single dose
Experimental: Arm #4 Single dose, double blind treatment period	Drug: LAS100977; Dry powder inhalation,Once daily, single dose
Active Comparator: Arm #5 Single dose, double blind treatment period	Drug: Reference; Dry powder inhalation (capsule),single dose
Placebo Comparator: Arm #6 Single dose, double blind treatment period	Drug: Placebo; Dry powder inhalation or Dry powder inhalation (capsule),Once daily, single dose
Experimental: Arm #1 Single dose, double blind treatment period	Drug: LAS100977; Dry powder inhalation,Once daily, single dose

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) [Day 2]

   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

Secondary Outcome Measures

1. Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve [Day 1]

   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

2. Change From Baseline in Forced Expiratory Volume in One Second (FEV1) [Up to Day 2]

   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

3. Absolute Forced Expiratory Volume in One Second (FEV1) Values [Up to Day 2]

   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

4. Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) [Day 1]

   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

5. Time to Peak Forced Expiratory Volume in One Second (FEV1) [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

6. Change From Baseline in Trough Forced Vital Capacity (FVC) [Day 2]

   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

7. Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve [Day 1]

   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

8. Change From Baseline in Forced Vital Capacity (FVC) [Up to Day 2]

   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

9. Absolute Forced Vital Capacity (FVC) Values [Up to Day 2]

   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

10. Change From Baseline in Peak Forced Vital Capacity (FVC) [Day 1]

    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

11. Time to Peak Forced Vital Capacity (FVC) [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

12. Change From Baseline in Inspiratory Capacity (IC) [Up to Day 2]

    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

13. Absolute Inspiratory Capacity (IC) Values [Up to Day 2]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males and non-pregnant, non-lactating females aged 40 or older.

2. Patients with a clinical diagnosis of COPD, according to the GOLD guidelines and stable airway obstruction.

3. Patients with a post-salbutamol FEV1 equal to or greater than 30% of the predicted value and less than 80% of the predicted value

4. Post-salbutamol FEV1/FVC < 70% at screening visit.

5. Pre-dose FEV1 value of first treatment period within the range of 80-120% of the FEV1 measured at screening prior to salbutamol inhalation.

6. Current, or ex-cigarette smokers (former) with a smoking history of at least 10 pack-years.

7. Patients whose COPD symptoms at the time of randomisation are stable compared to the Screening visit, according to the investigator's medical judgment.

Exclusion Criteria:

1. History or current diagnosis of asthma.

2. A respiratory tract infection or COPD exacerbation in the six weeks prior to the screening visit.

3. Patients who have been hospitalised for an acute COPD exacerbation in the 3 months prior to screening visit.

4. Clinically significant respiratory conditions other than COPD condition.

5. Clinically significant cardiovascular conditions.

6. Patients unable to properly use a dry powder or pMDI inhaler device or unable to perform acceptable spirometry.

7. Clinically relevant abnormalities laboratory, ECG parameters or physical examination results at the screening evaluation that in the investigator's opinion, preclude study participation.

8. Patients who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a particular prohibited medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Almirall Investigational Sites#5	Berlin		Germany	14050
2	Almirall Investigational Sites#2	Berlin		Germany	14057
3	Almirall Investigational Sites#6	Frankfurt		Germany	60596
4	Almirall Investigational Sites#3	Grosshansdorf		Germany	22927
5	Almirall Investigational Sites#7	Hamburg		Germany	20354
6	Almirall Investigational Sites#8	Lübeck		Germany	23552
7	Almirall Investigational Sites#1	Mainz		Germany	55131
8	Almirall Investigational Sites#4	Wiesbaden		Germany	65187

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Carol Astbury, PhD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR Synopsis

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01425814
• Other Study ID Numbers: M/100977/25; LBC25
• First Posted: Aug 30, 2011
• Last Update Posted: Apr 10, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by AstraZeneca: COPD
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details	The study was conducted in 9 sites in Germany, 8 of which randomized patients
Pre-assignment Detail	Screening took place 14±2 days before randomization. After screening, eligible patients entered a run-in period to assess clinical stability. A total of 87 patients were screened, of whom 70 patients were assessed as eligible and randomized; 17 were not randomized due to screening failure (primarily non-fulfillment of inclusion/exclusion criteria)

Arm/Group Title	Sequence A	Sequence B	Sequence C	Sequence D	Sequence E	Sequence F
Arm/Group Description	Indacaterol 150 μg - LAS100977 10 μg - Placebo - LAS100977 0.625 μg - LAS100977 5 μg- LAS100977 2.5 μg	LAS100977 10 μg - LAS100977 0.625 μg - Indacaterol 150 μg - LAS100977 2.5 μg - Placebo - LAS100977 5 μg	LAS100977 0.625 μg - LAS100977 2.5 μg - LAS100977 10 μg - LAS100977 5 μg - Indacaterol 150 μg - Placebo	LAS100977 2.5 μg - LAS100977 5 μg - LAS100977 0.625 μg - Placebo - LAS100977 10 μg - Indacaterol 150 μg	LAS100977 5 μg - Placebo - LAS100977 2.5 μg - Indacaterol 150 μg - LAS100977 0.625 μg - LAS100977 10 μg	Placebo - Indacaterol 150 μg - LAS100977 5 μg - LAS100977 10 μg - LAS100977 2.5 μg - LAS100977 0.625 μg
Period Title: Period 1
STARTED	12	11	12	10	12	13
COMPLETED	12	10	12	10	12	13
NOT COMPLETED	0	1	0	0	0	0
Period Title: Period 1
STARTED	12	10	12	10	12	13
COMPLETED	12	9	12	10	12	13
NOT COMPLETED	0	1	0	0	0	0
Period Title: Period 1
STARTED	12	9	12	10	12	13
COMPLETED	12	9	12	10	12	12
NOT COMPLETED	0	0	0	0	0	1
Period Title: Period 1
STARTED	12	9	12	10	12	12
COMPLETED	11	9	11	10	12	12
NOT COMPLETED	1	0	1	0	0	0
Period Title: Period 1
STARTED	11	9	11	10	12	12
COMPLETED	11	9	10	10	12	11
NOT COMPLETED	0	0	1	0	0	1

Baseline Characteristics

Arm/Group Title	Overall Population
Arm/Group Description	All patients who were randomized and received at least one dose of investigational medicinal product
Overall Participants	70
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.2 (7.7)
Sex: Female, Male (Count of Participants)
Female	26 37.1%
Male	44 62.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1)
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	Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Least Squares Mean (Standard Error) [Liters]	-0.035 (0.024)	0.066 (0.024)	0.168 (0.024)	0.198 (0.024)	0.223 (0.024)	0.076 (0.024)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, LAS100977 10 μg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.259
	Confidence Interval	(2-Sided) 95%; 0.219 to 0.298
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, LAS100977 5 μg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.233
	Confidence Interval	(2-Sided) 95%; 0.194 to 0.273
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, LAS100977 2.5 μg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.203
	Confidence Interval	(2-Sided) 95%; 0.164 to 0.242
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, LAS100977 0.625 μg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.102
	Confidence Interval	(2-Sided) 95%; 0.062 to 0.141
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve
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	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Change from baseline in FEV1 AUC0-12	-0.003 (0.012)	0.168 (0.021)	0.243 (0.021)	0.247 (0.021)	0.288 (0.022)	0.134 (0.017)
Change from baseline in FEV1 AUC0-24	-0.032 (0.013)	0.121 (0.021)	0.205 (0.022)	0.222 (0.021)	0.262 (0.024)	0.104 (0.018)
Change from baseline in FEV1 AUC12-24	-0.062 (0.016)	0.077 (0.023)	0.166 (0.024)	0.196 (0.021)	0.235 (0.021)	0.073 (0.021)

3. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
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	Up to Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Baseline	1.475 (0.059)	1.506 (0.065)	1.472 (0.062)	1.483 (0.063)	1.493 (0.065)	1.488 (0.064)
Day 1 0.08 hr	-0.005 (0.013)	0.044 (0.011)	0.090 (0.011)	0.085 (0.012)	0.117 (0.016)	0.103 (0.014)
Day 1 0.25 hr	0.006 (0.013)	0.087 (0.016)	0.155 (0.015)	0.161 (0.015)	0.191 (0.019)	0.132 (0.016)
Day 1 0.5 hr	0.018 (0.015)	0.126 (0.019)	0.186 (0.018)	0.202 (0.019)	0.217 (0.021)	0.150 (0.017)
Day 1 1 hr	0.010 (0.015)	0.151 (0.020)	0.217 (0.021)	0.218 (0.018)	0.240 (0.023)	0.156 (0.016)
Day 1 2 hr	0.002 (0.016)	0.166 (0.022)	0.230 (0.021)	0.245 (0.019)	0.261 (0.024)	0.161 (0.019)
Day 1 3 hr	0.018 (0.014)	0.201 (0.022)	0.287 (0.022)	0.274 (0.024)	0.321 (0.023)	0.184 (0.020)
Day 1 4 hr	0.015 (0.014)	0.225 (0.021)	0.308 (0.023)	0.308 (0.024)	0.341 (0.173)	0.179 (0.018)
Day 1 6 hr	-0.005 (0.017)	0.216 (0.028)	0.276 (0.024)	0.276 (0.022)	0.311 (0.031)	0.135 (0.018)
Day 1 8 hr	0.007 (0.016)	0.169 (0.025)	0.260 (0.025)	0.263 (0.024)	0.313 (0.025)	0.124 (0.021)
Day 1 12 hr	-0.047 (0.017)	0.115 (0.025)	0.189 (0.027)	0.202 (0.027)	0.271 (0.026)	0.085 (0.023)
Day 1 14 hr	-0.067 (0.020)	0.099 (0.026)	0.180 (0.026)	0.214 (0.24)	0.250 (0.026)	0.087 (0.022)
Day 2 23 hr	-0.066 (0.017)	0.036 (0.023)	0.134 (0.026)	0.166 (0.022)	0.211 (0.030)	0.050 (0.022)
Day 2 24 hr	-0.018 (0.019)	0.093 (0.023)	0.184 (0.025)	0.205 (0.021)	0.236 (0.027)	0.088 (0.020)
Day 2 36 hr	-0.020 (0.020)	0.040 (0.024)	0.104 (0.022)	0.083 (0.023)	0.116 (0.024)	0.036 (0.021)

4. Secondary Outcome

Title	Absolute Forced Expiratory Volume in One Second (FEV1) Values
Description	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	Up to Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Baseline	1.475 (0.059)	1.506 (0.065)	1.472 (0.062)	1.483 (0.063)	1.493 (0.065)	1.488 (0.064)
Day 1 0.08 hr	1.474 (0.060)	1.549 (0.064)	1.561 (0.064)	1.568 (0.062)	1.610 (0.065)	1.585 (0.064)
Day 1 0.25 hr	1.482 (0.059)	1.592 (0.064)	1.627 (0.063)	1.644 (0.064)	1.673 (0.066)	1.620 (0.063)
Day 1 0.5 hr	1.494 (0.060)	1.640 (0.064)	1.658 (0.063)	1.685 (0.065)	1.708 (0.067)	1.683 (0.065)
Day 1 1 hr	1.485 (0.061)	1.657 (0.066)	1.688 (0.065)	1.701 (0.067)	1.733 (0.069)	1.624 (0.061)
Day 1 2 hr	1.477 (0.061)	1.671 (0.067)	1.701 (0.067)	1.729 (0.067)	1.754 (0.068)	1.642 (0.066)
Day 1 3 hr	1.494 (0.061)	1.707 (0.069)	1.758 (0.068)	1.758 (0.069)	1.814 (0.071)	1.672 (0.066)
Day 1 4 hr	1.491 (0.061)	1.730 (0.068)	1.780 (0.068)	1.790 (0.070)	1.840 (0.073)	1.677 (0.067)
Day 1 6 hr	1.477 (0.062)	1.721 (0.070)	1.748 (0.070)	1.759 (0.069)	1.804 (0.074)	1.623 (0.065)
Day 1 8 hr	1.490 (0.062)	1.674 (0.070)	1.732 (0.070)	1.746 (0.070)	1.806 (0.073)	1.612 (0.065)
Day 1 12 hr	1.428 (0.061)	1.629 (0.069)	1.660 (0.066)	1.686 (0.068)	1.761 (0.073)	1.565 (0.067)
Day 1 14 hr	1.409 (0.061)	1.605 (0.068)	1.646 (0.068)	1.693 (0.069)	1.740 (0.072)	1.585 (0.065)
Day 2 23 hr	1.411 (0.061)	1.542 (0.068)	1.606 (0.070)	1.649 (0.070)	1.701 (0.074)	1.538 (0.064)
Day 2 24 hr	1.464 (0.062)	1.599 (0.070)	1.655 (0.071)	1.688 (0.070)	1.726 (0.073)	1.576 (0.066)
Day 2 36 hr	1.464 (0.064)	1.564 (0.068)	1.575 (0.068)	1.566 (0.069)	1.607 (0.069)	1.524 (0.064)

5. Secondary Outcome

Title	Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
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	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Least Squares Mean (Standard Error) [Liters]	0.098 (0.016)	0.290 (0.025)	0.351 (0.022)	0.350 (0.023)	0.391 (0.024)	0.263 (0.019)

6. Secondary Outcome

Title	Time to Peak Forced Expiratory Volume in One Second (FEV1)
Description	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	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Mean (Standard Error) [Hours]	2.5 (0.2)	3.4 (0.2)	3.5 (0.2)	3.7 (0.2)	4.0 (0.2)	2.9 (0.2)

7. Secondary Outcome

Title	Change From Baseline in Trough Forced Vital Capacity (FVC)
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	Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Least Squares Mean (Standard Error) [Liters]	-0.079 (0.044)	0.067 (0.044)	0.180 (0.044)	0.217 (0.044)	0.254 (0.044)	0.088 (0.044)

8. Secondary Outcome

Title	Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve
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	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Change from baseline in FVC AUC0-12	0.026 (0.026)	0.253 (0.037)	0.297 (0.036)	0.306 (0.034)	0.372 (0.037)	0.237 (0.033)
Change from baseline in FVC AUC0-24	-0.034 (0.027)	0.170 (0.036)	0.253 (0.039)	0.272 (0.035)	0.328 (0.038)	0.175 (0.033)
Change from baseline in FVC AUC12-24	-0.096 (0.031)	0.089 (0.039)	0.208 (0.045)	0.236 (0.039)	0.284 (0.042)	0.114 (0.037)

9. Secondary Outcome

Title	Change From Baseline in Forced Vital Capacity (FVC)
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	Up to Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Baseline	3.165 (0.101)	3.195 (0.104)	3.137 (0.102)	3.153 (0.094)	3.212 (0.108)	3.190 (0.106)
Day 1 0.08 hr	0.048 (0.026)	0.098 (0.027)	0.166 (0.034)	0.178 (0.027)	0.267 (0.040)	0.221 (0.034)
Day 1 0.25 hr	0.004 (0.027)	0.140 (0.033)	0.193 (0.037)	0.212 (0.033)	0.264 (0.036)	0.192 (0.035)
Day 1 0.5 hr	0.127 (0.085)	0.191 (0.035)	0.232 (0.037)	0.263 (0.036)	0.277 (0.037)	0.246 (0.036)
Day 1 1 hr	0.052 (0.029)	0.242 (0.041)	0.263 (0.043)	0.241 (0.036)	0.289 (0.042)	0.246 (0.041)
Day 1 2 hr	0.036 (0.035)	0.224 (0.041)	0.0269 (0.040)	0.300 (0.035)	0.303 (0.042)	0.244 (0.036)
Day 1 3 hr	0.020 (0.026)	0.248 (0.044)	0.338 (0.041)	0.325 (0.041)	0.392 (0.039)	0.274 (0.037)
Day 1 4 hr	0.016 (0.030)	0.297 (0.042)	0.379 (0.039)	0.337 (0.042)	0.402 (0.035)	0.254 (0.035)
Day 1 6 hr	0.036 (0.034)	0.340 (0.048)	0.327 (0.044)	0.348 (0.042)	0.415 (0.044)	0.231 (0.036)
Day 1 8 hr	0.048 (0.037)	0.263 (0.045)	0.309 (0.044)	0.335 (0.040)	0.425 (0.050)	0.266 (0.046)
Day 1 12 hr	-0.035 (0.038)	0.198 (0.048)	0.259 (0.046)	0.272 (0.050)	0.329 (0.048)	0.182 (0.047)
Day 1 14 hr	-0.110 (0.043)	0.107 (0.047)	0.236 (0.050)	0.266 (0.043)	0.315 (0.046)	0.148 (0.045)
Day 2 23 hr	-0.093 (0.037)	0.039 (0.042)	0.153 (0.050)	0.187 (0.044)	0.244 (0.051)	0.063 (0.041)
Day 2 24 hr	-0.076 (0.035)	0.090 (0.039)	0.186 (0.038)	0.207 (0.039)	0.243 (0.046)	0.100 (0.040)
Day 2 36 hr	-0.023 (0.037)	0.063 (0.040)	0.114 (0.045)	0.059 (0.038)	0.140 (0.040)	0.084 (0.040)

10. Secondary Outcome

Title	Absolute Forced Vital Capacity (FVC) Values
Description	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	Up to Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Baseline	3.165 (0.101)	3.195 (0.104)	3.137 (0.102)	3.153 (0.094)	3.212 (0.108)	3.190 (0.106)
Day 1 0.08 hr	3.205 (0.106)	3.293 (0.112)	3.318 (0.105)	3.331 (0.100)	3.479 (0.116)	3.418 (0.117)
Day 1 0.25 hr	3.169 (0.098)	3.335 (0.109)	3.329 (0.102)	3.365 (0.100)	3.455 (0.111)	3.382 (0.107)
Day 1 0.5 hr	3.292 (0.126)	3.399 (0.110)	3.368 (0.105)	3.417 (0.101)	3.488 (0.112)	3.441 (0.110)
Day 1 1 hr	3.217 (0.104)	3.436 (0.110)	3.400 (0.107)	3.394 (0.102)	3.501 (0.114)	3.415 (0.111)
Day 1 2 hr	3.201 (0.101)	3.418 (0.111)	3.406 (0.107)	3.454 (0.102)	3.514 (0.109)	3.415 (0.108)
Day 1 3 hr	3.185 (0.099)	3.443 (0.109)	3.475 (0.106)	3.478 (0.103)	3.603 (0.116)	3.464 (0.110)
Day 1 4 hr	3.181 (0.101)	3.492 (0.108)	3.516 (0.103)	3.478 (0.099)	3.608 (0.114)	3.448 (0.110)
Day 1 6 hr	3.220 (0.097)	3.535 (0.118)	3.464 (0.109)	3.501 (0.109)	3.626 (0.119)	3.421 (0.109)
Day 1 8 hr	3.232 (0.103)	3.458 (0.114)	3.445 (0.110)	3.488 (0.107)	3.636 (0.122)	3.469 (0.116)
Day 1 12 hr	3.130 (0.105)	3.406 (0.118)	3.396 (0.108)	3.425 (0.105)	3.534 (0.119)	3.367 (0.115)
Day 1 14 hr	3.055 (0.107)	3.302 (0.112)	3.359 (0.111)	3.411 (0.107)	3.520 (0.118)	3.348 (0.118)
Day 2 23 hr	3.075 (0.108)	3.233 (0.111)	3.290 (0.107)	3.341 (0.107)	3.448 (0.117)	3.257 (0.106)
Day 2 24 hr	3.095 (0.103)	3.284 (0.109)	3.323 (0.104)	3.360 (0.102)	3.447 (0.110)	3.295 (0.107)
Day 2 36 hr	3.145 (0.102)	3.289 (0.109)	3.251 (0.108)	3.212 (0.102)	3.345 (0.110)	3.274 (0.105)

11. Secondary Outcome

Title	Change From Baseline in Peak Forced Vital Capacity (FVC)
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	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Least Squares Mean (Standard Error) [Liters]	0.332 (0.050)	0.484 (0.050)	0.523 (0.050)	0.532 (0.050)	0.575 (0.050)	0.470 (0.050)

12. Secondary Outcome

Title	Time to Peak Forced Vital Capacity (FVC)
Description	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	Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Mean (Standard Error) [Hours]	2.4 (0.3)	3.6 (0.3)	3.4 (0.2)	3.1 (0.2)	3.6 (0.3)	2.6 (0.3)

13. Secondary Outcome

Title	Change From Baseline in Inspiratory Capacity (IC)
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
Time Frame	Up to Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Baseline	2.240 (0.082)	2.239 (0.078)	2.234 (0.075)	2.254 (0.077)	2.237 (0.077)	2.246 (0.076)
Day 1 4 hr	0.004 (0.037)	0.260 (0.039)	0.239 (0.040)	0.316 (0.043)	0.370 (0.043)	0.215 (0.036)
Day 2 24 hr	-0.047 (0.040)	0.110 (0.037)	0.157 (0.037)	0.174 (0.038)	0.273 (0.046)	0.136 (0.035)

14. Secondary Outcome

Title	Absolute Inspiratory Capacity (IC) Values
Description	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
Time Frame	Up to Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	LAS100977 0.625 μg	LAS100977 2.5 μg	LAS100977 5 μg	LAS100977 10 μg	Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Genuair® device	Single dose administered by inhalation from the Breezhaler® inhaler
Measure Participants	68	67	66	66	67	68
Baseline	2.240 (0.082)	2.239 (0.078)	2.234 (0.075)	2.254 (0.077)	2.237 (0.077)	2.246 (0.076)
Day 1 4 hr	2.279 (0.076)	2.504 (0.081)	2.473 (0.083)	2.548 (0.088)	2.623 (0.088)	2.447 (0.079)
Day 2 24 hr	2.203 (0.074)	2.374 (0.082)	2.398 (0.085)	2.402 (0.081)	2.543 (0.086)	2.380 (0.077)

Adverse Events

Time Frame	Up to 14 (±2) days after the last investigational medicinal product administration
Arm/Group Title	Placebo		LAS100977 0.625 μg		LAS100977 2.5 μg		LAS100977 5 μg		LAS100977 10 μg		Indacaterol 150 μg
Arm/Group Description	Single dose administered by inhalation from the Genuair® device and the Breezhaler® inhaler		Single dose administered by inhalation from the Genuair® device		Single dose administered by inhalation from the Genuair® device		Single dose administered by inhalation from the Genuair® device		Single dose administered by inhalation from the Genuair® device		Single dose administered by inhalation from the Breezhaler® inhaler
All Cause Mortality
	Placebo		LAS100977 0.625 μg		LAS100977 2.5 μg		LAS100977 5 μg		LAS100977 10 μg		Indacaterol 150 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		LAS100977 0.625 μg		LAS100977 2.5 μg		LAS100977 5 μg		LAS100977 10 μg		Indacaterol 150 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/67 (0%)		0/66 (0%)		1/66 (1.5%)		1/67 (1.5%)		0/68 (0%)
Nervous system disorders
Dizziness	0/68 (0%)		0/67 (0%)		0/66 (0%)		0/66 (0%)		1/67 (1.5%)		0/68 (0%)
Respiratory, thoracic and mediastinal disorders
COPD exacerbation	0/68 (0%)		0/67 (0%)		0/66 (0%)		1/66 (1.5%)		0/67 (0%)		0/68 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		LAS100977 0.625 μg		LAS100977 2.5 μg		LAS100977 5 μg		LAS100977 10 μg		Indacaterol 150 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/68 (2.9%)		4/67 (6%)		1/66 (1.5%)		1/66 (1.5%)		2/67 (3%)		5/68 (7.4%)
Infections and infestations
Nasopharyngitis	2/68 (2.9%)		4/67 (6%)		1/66 (1.5%)		1/66 (1.5%)		2/67 (3%)		5/68 (7.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Publication and/or presentation, whether complete or partial, of any part of the data or results of this trial will be subjected to revision and written agreement between the investigator and Sponsor