Trial Outcomes & Findings for BI 409306 Cardiac Safety Trial in Healthy Volunteers (NCT NCT02438683)

Results Overview

Slope of the placebo-corrected change from baseline in resting heart rate (ΔΔHR) vs. plasma concentration of BI 409306, as assessed from 0 to 10 hours (h) after intake of trial medication. The predicted mean value (90% CI) of ΔΔHR at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Primary analysis excluded measurement with missing values. Patients with available data were included.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

Baseline and up to 10 hours

Results posted on

2024-10-26

Participant Flow

Actual number of subjects enrolled in fact represents entered / randomized subjects due to the study set up.

Screening included informed consent, physical examination, vital signs, Holter Electrocardiogram (ECG), ECG, laboratory, demographics, medical history, Columbia Suicide Severity Rating Scale, cardiopulmonary exercise, concomitant therapy, review of inclusion/exclusion criteria. Subjects genotyped as CYP2C19 poor metabolizers were not to be treated.

Participant milestones

Participant milestones
Measure	Placebo /50 mg/ 200 mg of BI 409306 Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	Placebo /200 mg/ 50 mg of BI 409306 Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	50 mg / Placebo / 200 mg of BI 409306 Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	50 mg / 200 mg / Placebo of BI 409306 Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	200 mg / Placebo / 50 mg of BI 409306 Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	200 mg / 50 mg / Placebo of BI 409306 Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.
Overall Study STARTED	4	3	2	3	4	4
Overall Study COMPLETED	3	3	2	3	4	4
Overall Study NOT COMPLETED	1	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo /50 mg/ 200 mg of BI 409306 Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	Placebo /200 mg/ 50 mg of BI 409306 Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	50 mg / Placebo / 200 mg of BI 409306 Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	50 mg / 200 mg / Placebo of BI 409306 Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	200 mg / Placebo / 50 mg of BI 409306 Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	200 mg / 50 mg / Placebo of BI 409306 Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.
Overall Study Adverse Event	1	0	0	0	0	0

Baseline Characteristics

BI 409306 Cardiac Safety Trial in Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo /50 mg/ 200 mg of BI 409306 n=4 Participants Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	Placebo /200 mg/ 50 mg of BI 409306 n=3 Participants Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	50 mg / Placebo / 200 mg of BI 409306 n=2 Participants Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	50 mg / 200 mg / Placebo of BI 409306 n=3 Participants Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	200 mg / Placebo / 50 mg of BI 409306 n=4 Participants Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	200 mg / 50 mg / Placebo of BI 409306 n=4 Participants Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3.	Total n=20 Participants Total of all reporting groups
Age, Continuous	28.8 Years STANDARD_DEVIATION 10.9 • n=5 Participants	36.0 Years STANDARD_DEVIATION 9.2 • n=7 Participants	31.0 Years STANDARD_DEVIATION 5.7 • n=5 Participants	28.0 Years STANDARD_DEVIATION 3.0 • n=4 Participants	30.3 Years STANDARD_DEVIATION 8.2 • n=21 Participants	37.8 Years STANDARD_DEVIATION 9.5 • n=8 Participants	32.1 Years STANDARD_DEVIATION 8.4 • n=8 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=8 Participants	0 Participants n=8 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=8 Participants	20 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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=8 Participants	0 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=8 Participants	20 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	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=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	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=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	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=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=8 Participants	19 Participants n=8 Participants
Race (NIH/OMB) More than one race	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=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	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=8 Participants	0 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline and up to 10 hours

Population: The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the electrocardiogram (ECG) set (all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment in 1 treatment period for at least 1 ECG interval endpoint) who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups are not mutually exclusive.

Slope of the placebo-corrected change from baseline in resting heart rate (ΔΔHR) vs. plasma concentration of BI 409306, as assessed from 0 to 10 hours (h) after intake of trial medication. The predicted mean value (90% CI) of ΔΔHR at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Primary analysis excluded measurement with missing values. Patients with available data were included.

Outcome measures

Outcome measures
Measure	BI 409306 50 mg Under Resting Conditions n=16 Participants Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.	BI 409306 200 mg Under Resting Conditions n=16 Participants Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.
Slope of the Placebo-corrected Change From Baseline of Heart Rate at Rest and Plasma Concentration Between 0 to 10 Hours	0.80 beats/min Interval -0.76 to 2.36	5.46 beats/min Interval 2.44 to 8.49

PRIMARY outcome

Timeframe: Baseline and up to 4 hours

Population: The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive.

For 50 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table.

Outcome measures

Outcome measures
Measure	BI 409306 50 mg Under Resting Conditions n=17 Participants Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.	BI 409306 200 mg Under Resting Conditions n=18 Participants Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.
Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 50 mg Dose Group	4.33 beats/min Standard Error 1.33	0.48 beats/min Standard Error 1.28

PRIMARY outcome

Timeframe: Baseline and up to 4 hours

Population: The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive.

For 200 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table.

Outcome measures

Outcome measures
Measure	BI 409306 50 mg Under Resting Conditions n=17 Participants Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.	BI 409306 200 mg Under Resting Conditions n=18 Participants Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.
Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 200 mg Dose Group	5.85 beats/min Standard Error 1.35	0.92 beats/min Standard Error 1.33

SECONDARY outcome

Timeframe: Baseline and up to 10 hours

Population: The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the electrocardiogram set (ECGS) who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups are not mutually exclusive.

Slope of placebo-corrected change from baseline in resting Fridericia correction formula QTcF vs. plasma concentration of BI 409306, as assessed from 0 to 10 h after intake of trial medication. The predicted mean value (90% CI) of ΔΔQTcF at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Patients with available data were included.

Outcome measures

Outcome measures
Measure	BI 409306 50 mg Under Resting Conditions n=16 Participants Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.	BI 409306 200 mg Under Resting Conditions n=16 Participants Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.
Slope of Placebo-corrected Change From Baseline of Time Between Start of the Q Wave and End of the T Wave in an ECG Corrected for Heart Rate Using the Fridericia Correction Formula (QTcF) at Rest and Plasma Concentration Between 0 to 10 Hours	0.37 milliseconds (msec) Interval -1.45 to 2.19	2.09 milliseconds (msec) Interval -1.54 to 5.71

SECONDARY outcome

Timeframe: Baseline and up to 4 hours

Population: The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive.

For 50 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table.

Outcome measures

Outcome measures
Measure	BI 409306 50 mg Under Resting Conditions n=17 Participants Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.	BI 409306 200 mg Under Resting Conditions n=18 Participants Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.
Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 50 mg Dose Group	10.76 milliseconds (msec) Standard Error 1.39	6.22 milliseconds (msec) Standard Error 1.37

SECONDARY outcome

Timeframe: Baseline and up to 4 hours

Population: The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive.

For 200 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table.

Outcome measures

Outcome measures
Measure	BI 409306 50 mg Under Resting Conditions n=17 Participants Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.	BI 409306 200 mg Under Resting Conditions n=18 Participants Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.
Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 200 mg Dose Group	11.01 milliseconds (msec) Standard Error 1.42	6.28 milliseconds (msec) Standard Error 1.38

SECONDARY outcome

Timeframe: 20 minutes and 2 hours 20 minutes after drug intake

Population: The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the ECGS who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups are not mutually exclusive.

Slope of the placebo-corrected maximum heart rate during exercise vs. plasma concentration of BI 409306. Patients with available data were included. Exercise testing was completed before gMean Cmax was reached for BI 409306 200 mg arm. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table.

Outcome measures

Outcome measures
Measure	BI 409306 50 mg Under Resting Conditions n=16 Participants Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.	BI 409306 200 mg Under Resting Conditions Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions.
Slope of the Placebo-corrected Maximum Heart Rate During Exercise vs. Plasma Concentration of BI 409306	2.97 beats/min Interval 0.8 to 5.14	—

SECONDARY outcome

Timeframe: 20 minutes and 2 hours 20 minutes after drug intake

Population: The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the ECGS who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups were not mutually exclusive.

Slope of the placebo-corrected difference between maximum heart rate (HR) during exercise and recovery HR at 1 and 5 minutes (min) after the end of exercise vs. plasma concentration of BI 409306. The note "Not Calculated" represents that the plasma concentrations 1 min after the end of exercise did not reach gMean Cmax for the perticular arm. Patients with available data were included. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table.