Healthy
Conditions
Brief summary
The primary objective of this trial is to assess the effect of BI 409306 on the QT/QTc interval in healthy male and female volunteers as measured by the QTcF change from baseline compared with placebo. Secondary objectives are to show the assay sensitivity of the trial, by reproducing the typical effect of the positive control moxifloxacin on the QT/QTc interval, and to assess the effect of BI 409306 on heart rate.
Interventions
DRUGBI 409306
Film-coated tablet
DRUGMoxifloxacin
Film-coated tablet
DRUGPlacebo matching to BI 409306
Film-coated tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead single Electrocardiogram (ECG) and 12-lead Holter Electrocardiogram (ECG), and clinical laboratory tests * Age of 18 to 50 years (incl.) * Body mass index (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 * Male subjects, or female subjects who meet any of the following criteria starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion: * Use of adequate contraception, e.g. non-hormonal intrauterine device plus condom * Sexually abstinent * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) * Surgically sterilised (including hysterectomy) * Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside the range of 100 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 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) * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between 50 mg BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between 250 mg BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in QTcF at 3 Hours After Drug Administration (Assessment of Assay Sensitivity) | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 3 hours after drug administration. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in QTcF at 4 Hours After Drug Administration (Assessment of Assay Sensitivity) | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 4 hours after drug administration. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | Change from baseline in heart rate (HR) at each timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 50 milligram (mg) BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between moxifloxacin and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 50 milligram (mg) BI 409306 and placebo takes its minimum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 250 milligram (mg) BI 409306 and placebo takes its minimum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 250 milligram (mg) BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
| Change From Baseline in QTcF at 2 Hours After Drug Administration (Assessment of Assay Sensitivity) | Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration | QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 2 hours after drug administration. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations. |
Countries
Germany
Participant flow
Recruitment details
This was a randomized, placebo-controlled, double-blind trial with crossover design with 5 treatment periods, 15 treatment sequences based on a balanced, Prescott triple Latin square design with a wash-out period of at least 6 days between treatments: 50 mg BI 409306, 250 mg BI 409306, 400 mg moxifloxacin (positive control, open-label), placebo (2 periods).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated. Abbreviation: mg=milligram. There was a washout period of at least 6 days between treatments.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Total number of participants randomized and treated in this randomized, placebo-controlled, 5-period crossover trial where participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 milligram (mg) BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 46 | 0 / 45 | 0 / 46 | 0 / 45 |
| other Total, other adverse events | 2 / 45 | 3 / 46 | 12 / 45 | 36 / 46 | 3 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 46 | 0 / 45 | 0 / 46 | 0 / 45 |
Outcome results
Primary
Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum
QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between 250 mg BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | -0.0 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | 0.4 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | -0.4 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 1.0 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | -0.1 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | -6.8 milliseconds | Standard Error 0.7 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 minutes after drug intake= timepoint of maximum | -1.0 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | -0.9 milliseconds | Standard Error 0.7 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | -1.9 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | -6.3 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 minutes after drug intake | -1.4 milliseconds | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | -5.7 milliseconds | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 minutes after drug intake | 2.5 milliseconds | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 minutes after drug intake= timepoint of maximum | 4.7 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | 3.3 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | 2.7 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | 1.7 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | -0.7 milliseconds | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | 1.3 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 1.6 milliseconds | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | -7.3 milliseconds | Standard Error 0.9 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | -0.9 milliseconds | Standard Error 1 |
Comparison: MMRM was fitted to observations for 250 mg BI 409306 and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).90% CI: [4.4, 7.1]Mixed Models Analysis
Primary
Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum
QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between 50 mg BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | -0.1 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | 0.4 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | -0.5 milliseconds | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 1.0 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | -0.1 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | -7.0 milliseconds | Standard Error 0.7 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 minutes after drug intake | -1.0 milliseconds | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | -1.0 milliseconds | Standard Error 0.7 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | -2.0 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | -6.4 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 min after drug intake=timepoint of maximum | -1.5 milliseconds | Standard Error 0.4 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | -5.8 milliseconds | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 min after drug intake=timepoint of maximum | -0.2 milliseconds | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 minutes after drug intake | -0.8 milliseconds | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | 0.3 milliseconds | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | -0.4 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | -0.3 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | -1.7 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | -0.2 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 0.0 milliseconds | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | -7.3 milliseconds | Standard Error 0.9 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | -1.0 milliseconds | Standard Error 1 |
Comparison: MMRM was fitted to observations for 50 mg BI 409306 and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).90% CI: [0.2, 2.4]Mixed Models Analysis
Secondary
Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum
Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 250 milligram (mg) BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | 0.6 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | 1.4 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | 0.4 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 2.4 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | 0.8 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | 5.9 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 min after drug intake = timepoint of maximum | 0.3 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | 11.5 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | 1.6 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | 6.8 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 minutes (min) after drug intake | 0.6 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | 6.8 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 minutes (min) after drug intake | 8.9 beats / minute | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 min after drug intake = timepoint of maximum | 12.0 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | 8.1 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | 4.4 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | 3.2 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | 2.9 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | 1.9 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 3.2 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | 6.5 beats / minute | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | 11.5 beats / minute | Standard Error 0.7 |
Comparison: MMRM was fitted to observations for 250 mg BI 409306 and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).90% CI: [10.6, 12.8]Mixed Models Analysis
Secondary
Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum
Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 250 milligram (mg) BI 409306 and placebo takes its minimum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour and 30 minutes after drug intake | 0.6 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 3 hours after drug intake | 1.4 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour after drug intake | 0.4 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 4 hours after drug intake | 2.4 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours after drug intake | 0.8 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 8 hours after drug intake | 5.9 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 40 minutes after drug intake | 0.3 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 12 hours after drug intake=timepoint of minimum | 11.5 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours and 30 minutes after drug intake | 1.6 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 24 hours after drug intake | 6.8 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 20 min after drug intake | 0.6 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 24 hours after drug intake | 6.8 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 20 min after drug intake | 8.9 beats / minute | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 40 minutes after drug intake | 12.0 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour after drug intake | 8.1 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour and 30 minutes after drug intake | 4.4 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours after drug intake | 3.2 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours and 30 minutes after drug intake | 2.9 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 3 hours after drug intake | 1.9 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 4 hours after drug intake | 3.2 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 8 hours after drug intake | 6.5 beats / minute | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 12 hours after drug intake=timepoint of minimum | 11.5 beats / minute | Standard Error 0.7 |
Comparison: MMRM was fitted to observations for 250 mg BI 409306 and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).90% CI: [-1.3, 1.3]Mixed Models Analysis
Secondary
Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum
Change from baseline in heart rate (HR) at each timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 50 milligram (mg) BI 409306 and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | 0.7 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | 1.4 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | 0.5 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 2.5 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | 0.9 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | 6.0 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 minutes (min) after drug intake | 0.4 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | 11.6 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | 1.7 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | 6.9 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 min after drug intake = timepoint of maximum | 0.6 beats / minute | Standard Error 0.4 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 24 hours after drug intake | 5.7 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 20 min after drug intake = timepoint of maximum | 3.0 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 40 minutes (min) after drug intake | 2.5 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour after drug intake | 1.9 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 1 hour and 30 minutes after drug intake | 0.8 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours after drug intake | 0.8 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | 1.5 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 3 hours after drug intake | 1.9 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 4 hours after drug intake | 2.4 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 8 hours after drug intake | 6.5 beats / minute | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum | 12 hours after drug intake | 11.0 beats / minute | Standard Error 0.7 |
Comparison: MMRM was fitted to observations for 50 mg BI 409306 and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).90% CI: [1.4, 3.3]Mixed Models Analysis
Secondary
Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum
Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 50 milligram (mg) BI 409306 and placebo takes its minimum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 20 min after drug intake | 0.6 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour and 30 minutes after drug intake | 0.7 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 24 hours after drug intake = timepoint of minimum | 6.9 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours after drug intake | 0.9 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 40 minutes after drug intake | 0.4 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours and 30 minutes after drug intake | 1.7 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 12 hours after drug intake | 11.6 beats / minute | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 3 hours after drug intake | 1.4 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour after drug intake | 0.5 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 4 hours after drug intake | 2.5 beats / minute | Standard Error 0.4 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 8 hours after drug intake | 6.0 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 4 hours after drug intake | 2.4 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 8 hours after drug intake | 6.5 beats / minute | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 12 hours after drug intake | 11.0 beats / minute | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 24 hours after drug intake = timepoint of minimum | 5.7 beats / minute | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 20 min after drug intake | 3.0 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 40 minutes after drug intake | 2.5 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour after drug intake | 1.9 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 1 hour and 30 minutes after drug intake | 0.8 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours after drug intake | 0.8 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 2 hours and 30 minutes after drug intake | 1.5 beats / minute | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum | 3 hours after drug intake | 1.9 beats / minute | Standard Error 0.6 |
Comparison: MMRM was fitted to observations for 50 mg BI 409306 and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).90% CI: [-2.3, -0.1]Mixed Models Analysis
Secondary
Change From Baseline in QTcF at 2 Hours After Drug Administration (Assessment of Assay Sensitivity)
QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 2 hours after drug administration. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at 2 Hours After Drug Administration (Assessment of Assay Sensitivity) | -0.1 milliseconds | Standard Error 0.5 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at 2 Hours After Drug Administration (Assessment of Assay Sensitivity) | 11.8 milliseconds | Standard Error 0.7 |
Comparison: MMRM was fitted to the observations for moxifloxacin and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).p-value: 090% CI: [10.4, 13.4]Mixed Models Analysis
Secondary
Change From Baseline in QTcF at 3 Hours After Drug Administration (Assessment of Assay Sensitivity)
QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 3 hours after drug administration. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at 3 Hours After Drug Administration (Assessment of Assay Sensitivity) | 0.4 milliseconds | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at 3 Hours After Drug Administration (Assessment of Assay Sensitivity) | 11.4 milliseconds | Standard Error 0.9 |
Comparison: MMRM was fitted to the observations for moxifloxacin and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).p-value: 3e-890% CI: [9.3, 12.8]Mixed Models Analysis
Secondary
Change From Baseline in QTcF at 4 Hours After Drug Administration (Assessment of Assay Sensitivity)
QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 4 hours after drug administration. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at 4 Hours After Drug Administration (Assessment of Assay Sensitivity) | 1.0 milliseconds | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at 4 Hours After Drug Administration (Assessment of Assay Sensitivity) | 11.7 milliseconds | Standard Error 0.9 |
Comparison: MMRM was fitted to the observations for moxifloxacin and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).p-value: 2e-790% CI: [8.9, 12.4]Mixed Models Analysis
Secondary
Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum
QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between moxifloxacin and placebo takes its maximum. A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods. Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.
Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration
Population: ECG Set: This participant set included all randomized participants who received at least one dose of any trial medication and who had at least one on-treatment value for at least one electrocardiogram (ECG) endpoint, which was not excluded due to ECG-relevant important protocol deviations (e.g. the use of pro-arrhythmic medications).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 1 h 30 min after drug intake=timepoint of maximum | -0.1 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 3 hours after drug intake | 0.4 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 1 hour after drug intake | -0.5 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 4 hours after drug intake | 1.0 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 2 hours after drug intake | -0.1 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 8 hours after drug intake | -7.0 milliseconds | Standard Error 0.7 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 40 minutes after drug intake | -1.0 milliseconds | Standard Error 0.5 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 12 hours after drug intake | -0.9 milliseconds | Standard Error 0.7 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | -2.0 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 24 hours after drug intake | -6.5 milliseconds | Standard Error 0.6 |
| Placebo to BI 409306 in 2 Periods | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 20 min after drug intake | -1.5 milliseconds | Standard Error 0.4 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 24 hours after drug intake | -0.7 milliseconds | Standard Error 0.9 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 20 min after drug intake | -1.2 milliseconds | Standard Error 0.6 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 40 minutes after drug intake | 7.7 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 1 hour after drug intake | 11.4 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 1 h 30 min after drug intake=timepoint of maximum | 12.0 milliseconds | Standard Error 0.8 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 2 hours after drug intake | 11.8 milliseconds | Standard Error 0.7 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 2 hours and 30 minutes after drug intake | 8.4 milliseconds | Standard Error 0.9 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 3 hours after drug intake | 11.4 milliseconds | Standard Error 0.9 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 4 hours after drug intake | 11.7 milliseconds | Standard Error 0.9 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 8 hours after drug intake | 2.3 milliseconds | Standard Error 1 |
| 50 Milligram (mg) BI 409306 | Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum | 12 hours after drug intake | 5.0 milliseconds | Standard Error 1 |
Comparison: MMRM was fitted to the observations for moxifloxacin and the 2 placebo periods. MMRM with covariates 'period baseline', 'participant baseline' (=arithmetic mean of respective period baselines), fixed categorical effects 'treatment', 'period', and 'time', interaction terms 'period baseline-by-time', 'participant baseline-by-time', 'treatment-by-time', and 'period-by-time', 'participant' (random effect), and time within period as repeated measures per participant (covariance matrix=Unstructured).90% CI: [10.5, 13.6]Mixed Models Analysis