To Assess Safety, Tolerability and Pharmacokinetics of BI 443651 in Healthy Male Volunteers

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02706925
• Collaborator: (none)
• Enrollment: 63
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.7
• Patients Per Site Per Month: 23.1

Study Details

Study Description

Brief Summary

To investigate safety, tolerability and pharmacokinetics, following single doses of BI 443651

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: BI 443651; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses of BI 443651 in Healthy Male Volunteers in a Partially Randomised, Single Blind, Placebo-controlled Trial
• Actual Study Start Date: Mar 22, 2016
• Actual Primary Completion Date: Jun 12, 2016
• Actual Study Completion Date: Jun 13, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 443651	Drug: BI 443651
Placebo Comparator: Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Drug-related Adverse Events (AEs) [Up to 216 hours.]

   This outcome measure presents percentage of the subjects with drug-related AEs. The doses ranged from 10 μg to 3600 μg for the outcome measure [Percentage of subjects with drug-related Adverse Events (AEs)].

Secondary Outcome Measures

1. AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) [1.30 (hours: minutes) hours (h) before drug administration and 0:05h, 0:10h, 0:15h, 0:20h, 0:30h, 0:40h, 0:50h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h, 96:00h after drug administration.]

   This outcome measure presents area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz). Time frame note: The time points 72:00h, 96:00h below was only applicable for highest dose (and corresponding placebo subjects). Two blood sample for stability testing were taken at 3:00h time point from the Treatment C dose group only. The doses ranged from 10 μg to 3600 μg for the outcome measure [AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)].

2. Cmax (Maximum Measured Concentration of the Analyte in Plasma) [1.30 (hours: minutes) hours (h) before drug administration and 0:05h, 0:10h, 0:15h, 0:20h, 0:30h, 0:40h, 0:50h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h, 96:00h after drug administration.]

   This outcome measure presents maximum concentration of analyte in plasma (Cmax). Time frame note: The time points 72:00h, 96:00h below was only applicable for highest dose (and corresponding placebo subjects). Two blood sample for stability testing were taken at 3:00h time point from the Treatment C dose group only. The doses ranged from 10 μg to 3600 μg for the outcome measure [Cmax (maximum measured concentration of the analyte in plasma)].

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• Healthy male according to the investigators assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests

• Age of 18 to 50 years (incl.)

• BMI of 18.5 to 29.9 kg/m2 (incl.)

• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator

• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm

• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance

• Any evidence of a concomitant disease judged as clinically relevant by the investigator

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)

• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders

• History of relevant orthostatic hypotension, fainting spells, or blackouts

• Chronic or relevant acute infections

• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)

• Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication

• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval

• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication

• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)

• Inability to refrain from smoking on specified trial days

• Alcohol abuse (consumption of more 30 g per day for males)

• Drug abuse or positive drug screening

• Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial

• Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial

• Inability to comply with dietary regimen of trial site

• A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant ECG finding at screening

• A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)

• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

• The subject has a diagnosis history of pulmonary hyperreactivity.

• Estimated glomerular filtration rate (eGFR) below 80 mL/min

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Humanpharmakologisches Zentrum Biberach	Biberach		Germany	88397

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02706925
• Other Study ID Numbers: 1363.1; 2015-004395-30
• First Posted: Mar 11, 2016
• Last Update Posted: Jan 2, 2020
• Last Verified: Dec 1, 2019

Study Results

Participant Flow

Recruitment Details	This trial was performed as a partially randomised, placebo-controlled within parallel dose groups, single-blind trial.
Pre-assignment Detail	All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated.

Arm/Group Title	Placebo	BI 443651 10 μg	BI 443651 30 μg	BI 443651 100 μg	BI 443651 300 μg	BI 443651 900 μg	BI 443651 1800 μg	BI 443651 2700 μg	BI 443651 3600 μg
Arm/Group Description	Subjects were administered single dose of matching placebo to BI 443651 solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.
Period Title: Overall Study
STARTED	16	6	6	6	6	5	6	6	6
COMPLETED	16	6	6	6	6	5	6	6	6
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	BI 443651 10 μg	BI 443651 30 μg	BI 443651 100 μg	BI 443651 300 μg	BI 443651 900 μg	BI 443651 1800 μg	BI 443651 2700 μg	BI 443651 3600 μg	Total
Arm/Group Description	Subjects were administered single dose of matching placebo to BI 443651 solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Total of all reporting groups
Overall Participants	16	6	6	6	6	5	6	6	6	63
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	33.6 (9.3)	31.0 (7.5)	40.5 (7.2)	26.8 (1.9)	30.3 (5.1)	37.6 (8.3)	31.5 (7.8)	31.7 (10.0)	31.8 (9.7)	32.8 (8.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	16 100%	6 100%	6 100%	6 100%	6 100%	5 100%	6 100%	6 100%	6 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Drug-related Adverse Events (AEs)
Description	This outcome measure presents percentage of the subjects with drug-related AEs. The doses ranged from 10 μg to 3600 μg for the outcome measure [Percentage of subjects with drug-related Adverse Events (AEs)].
Time Frame	Up to 216 hours.

Outcome Measure Data

Analysis Population Description

Treated Set (TS): This subject set includes all subjects from the Randomised Set (RS) who were documented to have taken at least 1 dose of study drug.

Arm/Group Title	Placebo	BI 443651 10 μg	BI 443651 30 μg	BI 443651 100 μg	BI 443651 300 μg	BI 443651 900 μg	BI 443651 1800 μg	BI 443651 2700 μg	BI 443651 3600 μg
Arm/Group Description	Subjects were administered single dose of matching placebo to BI 443651 solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.
Measure Participants	16	6	6	6	6	5	6	6	6
Number [Percentage of subjects]	0.0	0.0	0.0	0.0	16.7	0.0	16.7	66.7	66.7

2. Secondary Outcome

Title	AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point)
Description	This outcome measure presents area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz). Time frame note: The time points 72:00h, 96:00h below was only applicable for highest dose (and corresponding placebo subjects). Two blood sample for stability testing were taken at 3:00h time point from the Treatment C dose group only. The doses ranged from 10 μg to 3600 μg for the outcome measure [AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)].
Time Frame	1.30 (hours: minutes) hours (h) before drug administration and 0:05h, 0:10h, 0:15h, 0:20h, 0:30h, 0:40h, 0:50h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h, 96:00h after drug administration.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set (PKS): This subject set includes all subjects from the TS on who received Boehringer Ingelheim (BI) 443651 and who provided at least 1 PK endpoint value that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.

Arm/Group Title	BI 443651 10 μg	BI 443651 30 μg	BI 443651 100 μg	BI 443651 300 μg	BI 443651 900 μg	BI 443651 1800 μg	BI 443651 2700 μg	BI 443651 3600 μg
Arm/Group Description	Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.
Measure Participants	6	6	6	6	5	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [pmol*h/L]	24.2 (54.7)	146 (69.4)	506 (42.5)	1860 (54.8)	5680 (57.3)	26400 (49.8)	39300 (34.3)	60700 (43.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BI 443651 10 μg, BI 443651 30 μg, BI 443651 100 μg, BI 443651 300 μg, BI 443651 900 μg, BI 443651 1800 μg, BI 443651 2700 μg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.2951
	Confidence Interval	(2-Sided) 95%; 1.2242 to 1.3660
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0352
	Estimation Comments	The model of dose proportionality was power model that describes the functional relationship between the dose and PK endpoints. Perfect dose proportionality would correspond to a slope of 1. Standard deviation is actually the standard error of slope.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 443651 10 μg, BI 443651 30 μg, BI 443651 100 μg, BI 443651 300 μg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.0880
	Confidence Interval	(2-Sided) 95%; 0.9128 to 1.2633
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0843
	Estimation Comments	The model of dose proportionality was power model that describes the functional relationship between the dose and PK endpoints. Perfect dose proportionality would correspond to a slope of 1. Standard deviation is actually the standard error of slope.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BI 443651 900 μg, BI 443651 1800 μg, BI 443651 2700 μg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.1846
	Confidence Interval	(2-Sided) 95%; 0.4791 to 1.8900
	Parameter Dispersion	Type: Standard Deviation; Value: 0.3328
	Estimation Comments	The model of dose proportionality was power model that describes the functional relationship between the dose and PK endpoints. Perfect dose proportionality would correspond to a slope of 1. Standard deviation is actually the standard error of slope.

3. Secondary Outcome

Title	Cmax (Maximum Measured Concentration of the Analyte in Plasma)
Description	This outcome measure presents maximum concentration of analyte in plasma (Cmax). Time frame note: The time points 72:00h, 96:00h below was only applicable for highest dose (and corresponding placebo subjects). Two blood sample for stability testing were taken at 3:00h time point from the Treatment C dose group only. The doses ranged from 10 μg to 3600 μg for the outcome measure [Cmax (maximum measured concentration of the analyte in plasma)].
Time Frame	1.30 (hours: minutes) hours (h) before drug administration and 0:05h, 0:10h, 0:15h, 0:20h, 0:30h, 0:40h, 0:50h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h, 96:00h after drug administration.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set (PKS): This subject set includes all subjects from the TS on who received BI 443651 and who provided at least 1 PK endpoint value that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.

Arm/Group Title	BI 443651 10 μg	BI 443651 30 μg	BI 443651 100 μg	BI 443651 300 μg	BI 443651 900 μg	BI 443651 1800 μg	BI 443651 2700 μg	BI 443651 3600 μg
Arm/Group Description	Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.
Measure Participants	6	6	6	6	5	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [pmol/L]	14.1 (20.7)	58.7 (81.6)	198 (35.5)	725 (41.1)	1700 (43.0)	7590 (60.2)	14400 (39.2)	19800 (56.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BI 443651 10 μg, BI 443651 30 μg, BI 443651 100 μg, BI 443651 300 μg, BI 443651 900 μg, BI 443651 1800 μg, BI 443651 2700 μg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.2114
	Confidence Interval	(2-Sided) 95%; 1.1409 to 1.2818
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0350
	Estimation Comments	The model of dose proportionality was power model that describes the functional relationship between the dose and PK endpoints. Perfect dose proportionality would correspond to a slope of 1. Standard deviation is actually the standard error of slope.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, BI 443651 10 μg, BI 443651 30 μg, BI 443651 100 μg, BI 443651 300 μg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.0771
	Confidence Interval	(2-Sided) 95%; 0.9696 to 1.1845
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0524
	Estimation Comments	The model of dose proportionality was power model that describes the functional relationship between the dose and PK endpoints. Perfect dose proportionality would correspond to a slope of 1. Standard deviation is actually the standard error of slope.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BI 443651 900 μg, BI 443651 1800 μg, BI 443651 2700 μg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.3969
	Confidence Interval	(2-Sided) 95%; 0.5563 to 2.2375
	Parameter Dispersion	Type: Standard Deviation; Value: 0.3965
	Estimation Comments	The model of dose proportionality was power model that describes the functional relationship between the dose and PK endpoints. Perfect dose proportionality would correspond to a slope of 1. Standard deviation is actually the standard error of slope.

Adverse Events

Time Frame	From first drug administration until 1 day after last drug administration, up to 70 days.
Arm/Group Title	Placebo		BI 443651 10 μg		BI 443651 30 μg		BI 443651 100 μg		BI 443651 300 μg		BI 443651 900 μg		BI 443651 1800 μg		BI 443651 2700 μg		BI 443651 3600 μg
Arm/Group Description	Subjects were administered single dose of matching placebo to BI 443651 solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.		Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.
All Cause Mortality
	Placebo		BI 443651 10 μg		BI 443651 30 μg		BI 443651 100 μg		BI 443651 300 μg		BI 443651 900 μg		BI 443651 1800 μg		BI 443651 2700 μg		BI 443651 3600 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		BI 443651 10 μg		BI 443651 30 μg		BI 443651 100 μg		BI 443651 300 μg		BI 443651 900 μg		BI 443651 1800 μg		BI 443651 2700 μg		BI 443651 3600 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		BI 443651 10 μg		BI 443651 30 μg		BI 443651 100 μg		BI 443651 300 μg		BI 443651 900 μg		BI 443651 1800 μg		BI 443651 2700 μg		BI 443651 3600 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/16 (25%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		2/5 (40%)		3/6 (50%)		4/6 (66.7%)		4/6 (66.7%)
Gastrointestinal disorders
Nausea	0/16 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Infections and infestations
Nasopharyngitis	1/16 (6.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Nervous system disorders
Headache	1/16 (6.3%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		2/5 (40%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Syncope	1/16 (6.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Psychiatric disorders
Dysphoria	0/16 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/16 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		3/6 (50%)		3/6 (50%)
Epistaxis	1/16 (6.3%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Throat irritation	0/16 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Erythema	0/16 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Vascular disorders
Haematoma	0/16 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.