Trial Outcomes & Findings for To Assess Safety, Tolerability and Pharmacokinetics of BI 443651 in Healthy Male Volunteers (NCT NCT02706925)

Last Updated: 2020-01-02

Results Overview

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 \[Percentage of subjects with drug-related Adverse Events (AEs)\].

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

63 participants

Primary outcome timeframe

Up to 216 hours.

Results posted on

2020-01-02

Participant Flow

This trial was performed as a partially randomised, placebo-controlled within parallel dose groups, single-blind trial.

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.

Participant milestones

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

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=16 Participants Subjects were administered single dose of matching placebo to BI 443651 solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 10 μg n=6 Participants Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 30 μg n=6 Participants Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 100 μg n=6 Participants Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 300 μg n=6 Participants Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 900 μg n=5 Participants Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 1800 μg n=6 Participants Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 2700 μg n=6 Participants Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 3600 μg n=6 Participants Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	Total n=63 Participants Total of all reporting groups
Age, Continuous	33.6 Years STANDARD_DEVIATION 9.3 • n=5 Participants	31.0 Years STANDARD_DEVIATION 7.5 • n=7 Participants	40.5 Years STANDARD_DEVIATION 7.2 • n=5 Participants	26.8 Years STANDARD_DEVIATION 1.9 • n=4 Participants	30.3 Years STANDARD_DEVIATION 5.1 • n=21 Participants	37.6 Years STANDARD_DEVIATION 8.3 • n=10 Participants	31.5 Years STANDARD_DEVIATION 7.8 • n=115 Participants	31.7 Years STANDARD_DEVIATION 10.0 • n=24 Participants	31.8 Years STANDARD_DEVIATION 9.7 • n=42 Participants	32.8 Years STANDARD_DEVIATION 8.4 • n=42 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	5 Participants n=10 Participants	6 Participants n=115 Participants	6 Participants n=24 Participants	6 Participants n=42 Participants	63 Participants n=42 Participants

PRIMARY outcome

Timeframe: Up to 216 hours.

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Subjects were administered single dose of matching placebo to BI 443651 solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 10 μg n=6 Participants Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 30 μg n=6 Participants Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 100 μg n=6 Participants Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 300 μg n=6 Participants Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 900 μg n=5 Participants Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 1800 μg n=6 Participants Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 2700 μg n=6 Participants Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 3600 μg n=6 Participants Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.
Percentage of Subjects With Drug-related Adverse Events (AEs)	0.0 Percentage of subjects	0.0 Percentage of subjects	0.0 Percentage of subjects	0.0 Percentage of subjects	16.7 Percentage of subjects	0.0 Percentage of subjects	16.7 Percentage of subjects	66.7 Percentage of subjects	66.7 Percentage of subjects

SECONDARY outcome

Timeframe: 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.

Population: 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.

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 \[AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)\].

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Subjects were administered single dose of matching placebo to BI 443651 solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 10 μg n=6 Participants Subjects were administered single dose of BI 443651 10 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 30 μg n=6 Participants Subjects were administered single dose of BI 443651 30 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 100 μg n=6 Participants Subjects were administered single dose of BI 443651 100 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 300 μg n=5 Participants Subjects were administered single dose of BI 443651 300 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 900 μg n=6 Participants Subjects were administered single dose of BI 443651 900 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 1800 μg n=6 Participants Subjects were administered single dose of BI 443651 1800 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 2700 μg n=6 Participants Subjects were administered single dose of BI 443651 2700 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.	BI 443651 3600 μg Subjects were administered single dose of BI 443651 3600 μg solution for inhalation per actuation via the RESPIMAT® inhaler orally.
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)	24.2 pmol*h/L Geometric Coefficient of Variation 54.7	146 pmol*h/L Geometric Coefficient of Variation 69.4	506 pmol*h/L Geometric Coefficient of Variation 42.5	1860 pmol*h/L Geometric Coefficient of Variation 54.8	5680 pmol*h/L Geometric Coefficient of Variation 57.3	26400 pmol*h/L Geometric Coefficient of Variation 49.8	39300 pmol*h/L Geometric Coefficient of Variation 34.3	60700 pmol*h/L Geometric Coefficient of Variation 43.9	—

SECONDARY outcome

Population: 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.

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 \[Cmax (maximum measured concentration of the analyte in plasma)\].