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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005132-34 | EudraCT Number | EudraCT |
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This trial will be conducted to further evaluate, in a controlled setting, potential cardiac effects of an anticipated therapeutic and supra-therapeutic dose of BI 409306 under resting and exercise conditions. Since the drug is being developed in part for a disease with an expectedly high number of elderly (AD), the characterization of cardiac safety of BI 409306 is considered to be important for the development of this compound.
This trial will be conducted to further evaluate, in a controlled setting, potential cardiac effects of an anticipated therapeutic and supra-therapeutic dose of BI 409306 under resting and exercise conditions.
Since the drug is being developed in part for a disease with an expectedly high number of elderly (AD), the characterization of cardiac safety of BI 409306 is considered to be important for the development of this compound.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo under resting/exercise conditions | Placebo Comparator | Participants received matching Placebo oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting/exercise conditions. |
|
| BI 409306 50 mg under resting/exercise conditions | Experimental | Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting/exercise conditions. |
|
| BI 409306 200 mg under resting/exercise conditions | Experimental | Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting/exercise conditions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 409306 | Drug | high dose, single dose, oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Slope of the Placebo-corrected Change From Baseline of Heart Rate at Rest and Plasma Concentration Between 0 to 10 Hours | Slope of the placebo-corrected change from baseline in resting heart rate (ΔΔHR) vs. plasma concentration of BI 409306, as assessed from 0 to 10 hours (h) after intake of trial medication. The predicted mean value (90% CI) of ΔΔHR at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Primary analysis excluded measurement with missing values. Patients with available data were included. | Baseline and up to 10 hours |
| Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 50 mg Dose Group | For 50 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table. | Baseline and up to 4 hours |
| Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 200 mg Dose Group | For 200 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table. |
| Measure | Description | Time Frame |
|---|---|---|
| Slope of Placebo-corrected Change From Baseline of Time Between Start of the Q Wave and End of the T Wave in an ECG Corrected for Heart Rate Using the Fridericia Correction Formula (QTcF) at Rest and Plasma Concentration Between 0 to 10 Hours | Slope of placebo-corrected change from baseline in resting Fridericia correction formula QTcF vs. plasma concentration of BI 409306, as assessed from 0 to 10 h after intake of trial medication. The predicted mean value (90% CI) of ΔΔQTcF at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Patients with available data were included. |
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Inclusion criteria:
- Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests.
Exclusion criteria:
Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
Repeated measurement of
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 PK of the trial medication (except appendectomy and simple hernia repair)
Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
History of relevant orthostatic hypotension, fainting spells, or blackouts
Chronic or relevant acute infections
History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication
Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval
Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication
Smoker (unless the subject quit smoking for at least 30 days prior to screening)
Alcohol abuse (consumption of more than 30 g per day)
Drug abuse or positive drug screening
Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
Inability to comply with dietary regimen of trial site
A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
Any suicidal ideation of type 2 to 5 on the C-SSRS in the past 12 months (i.e. active suicidal thought, active suicidal thought with method, active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
Any lifetime history of suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour).
In addition, the following trial-specific exclusion criteria apply:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1289.28.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
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| Label | URL |
|---|---|
| Related Info | View source |
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Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).
For more details refer to: https://www.mystudywindow.com/msw/datatransparency
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Screening included informed consent, physical examination, vital signs, Holter Electrocardiogram (ECG), ECG, laboratory, demographics, medical history, Columbia Suicide Severity Rating Scale, cardiopulmonary exercise, concomitant therapy, review of inclusion/exclusion criteria. Subjects genotyped as CYP2C19 poor metabolizers were not to be treated.
Actual number of subjects enrolled in fact represents entered / randomized subjects due to the study set up.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo /50 mg/ 200 mg of BI 409306 | Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| FG001 | Placebo /200 mg/ 50 mg of BI 409306 | Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| FG002 | 50 mg / Placebo / 200 mg of BI 409306 | Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| FG003 | 50 mg / 200 mg / Placebo of BI 409306 | Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| FG004 | 200 mg / Placebo / 50 mg of BI 409306 | Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| FG005 | 200 mg / 50 mg / Placebo of BI 409306 | Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The treated set (TS) consisted of all subjects who were documented to have taken at least 1 dose of trial medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo /50 mg/ 200 mg of BI 409306 | Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Slope of the Placebo-corrected Change From Baseline of Heart Rate at Rest and Plasma Concentration Between 0 to 10 Hours | Slope of the placebo-corrected change from baseline in resting heart rate (ΔΔHR) vs. plasma concentration of BI 409306, as assessed from 0 to 10 hours (h) after intake of trial medication. The predicted mean value (90% CI) of ΔΔHR at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Primary analysis excluded measurement with missing values. Patients with available data were included. | The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the electrocardiogram (ECG) set (all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment in 1 treatment period for at least 1 ECG interval endpoint) who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups are not mutually exclusive. | Posted | Geometric Mean | 90% Confidence Interval | beats/min | Baseline and up to 10 hours |
|
From drug administration until end of washout period or end of trial examination, up to 10 days.
The treated set (TS) consisted of all subjects who were documented to have taken at least 1 dose of trial medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo Under Resting Conditions | Participants received matching Placebo oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chromatopsia | Eye disorders | MedDRA 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| C000630656 | BI 409306 |
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| BI 409306 | Drug | low dose, single dose, oral administration |
|
| Placebo | Drug | single dose, oral administration |
|
| Baseline and up to 4 hours |
| Baseline and up to 10 hours |
| Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 50 mg Dose Group | For 50 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table. | Baseline and up to 4 hours |
| Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 200 mg Dose Group | For 200 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table. | Baseline and up to 4 hours |
| Slope of the Placebo-corrected Maximum Heart Rate During Exercise vs. Plasma Concentration of BI 409306 | Slope of the placebo-corrected maximum heart rate during exercise vs. plasma concentration of BI 409306. Patients with available data were included. Exercise testing was completed before gMean Cmax was reached for BI 409306 200 mg arm. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. | 20 minutes and 2 hours 20 minutes after drug intake |
| Slope of the Placebo Corrected Change From Maximum Heart Rate 1 and 5 Minutes After End of Exercise and Plasma Concentration | Slope of the placebo-corrected difference between maximum heart rate (HR) during exercise and recovery HR at 1 and 5 minutes (min) after the end of exercise vs. plasma concentration of BI 409306. The note "Not Calculated" represents that the plasma concentrations 1 min after the end of exercise did not reach gMean Cmax for the perticular arm. Patients with available data were included. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. | 20 minutes and 2 hours 20 minutes after drug intake |
| BG001 | Placebo /200 mg/ 50 mg of BI 409306 | Participants first received matching Placebo 250 mg, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| BG002 | 50 mg / Placebo / 200 mg of BI 409306 | Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 200 mg with 50 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| BG003 | 50 mg / 200 mg / Placebo of BI 409306 | Participants first received BI 409306 50 mg with 200 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 200 mg with 50 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| BG004 | 200 mg / Placebo / 50 mg of BI 409306 | Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received matching Placebo 250 mg, again after a separation phase of at least 6 days, they received BI 409306 50 mg with 200 mg matching placebo film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| BG005 | 200 mg / 50 mg / Placebo of BI 409306 | Participants first received BI 409306 200 mg with 50 mg matching placebo, after a separation phase of at least 6 days, they then received BI 409306 50 mg with 200 mg matching placebo, again after a separation phase of at least 6 days, they received matching Placebo 250 mg film-coated tablets. Every treatment is given oral as 2 single doses (with wash-out phase of approximately 48 hours) with 240 mL of water after a standardized light breakfast on Day 1 and Day 3. |
| BG006 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 | BI 409306 50 mg Under Resting Conditions | Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions. |
| OG001 | BI 409306 200 mg Under Resting Conditions | Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions. |
|
|
|
| Primary | Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 50 mg Dose Group | For 50 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table. | The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive. | Posted | Least Squares Mean | Standard Error | beats/min | Baseline and up to 4 hours |
|
|
|
|
| Primary | Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 200 mg Dose Group | For 200 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table. | The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive. | Posted | Least Squares Mean | Standard Error | beats/min | Baseline and up to 4 hours |
|
|
|
|
| Secondary | Slope of Placebo-corrected Change From Baseline of Time Between Start of the Q Wave and End of the T Wave in an ECG Corrected for Heart Rate Using the Fridericia Correction Formula (QTcF) at Rest and Plasma Concentration Between 0 to 10 Hours | Slope of placebo-corrected change from baseline in resting Fridericia correction formula QTcF vs. plasma concentration of BI 409306, as assessed from 0 to 10 h after intake of trial medication. The predicted mean value (90% CI) of ΔΔQTcF at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Patients with available data were included. | The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the electrocardiogram set (ECGS) who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups are not mutually exclusive. | Posted | Geometric Mean | 90% Confidence Interval | milliseconds (msec) | Baseline and up to 10 hours |
|
|
|
|
| Secondary | Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 50 mg Dose Group | For 50 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table. | The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive. | Posted | Least Squares Mean | Standard Error | milliseconds (msec) | Baseline and up to 4 hours |
|
|
|
|
| Secondary | Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 200 mg Dose Group | For 200 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table. | The electrocardiogram analysis set (ECGS) consisted of all subjects in the treated set who had at least 1 baseline and 1 post-baseline assessment (measured at rest) in 1 treatment period for at least 1 ECG interval endpoint. The ECGS was used for all ECG analyses except for those assessing the relationship between plasma concentration and ECG variables. Patients in the treatment groups are not mutually exclusive. | Posted | Least Squares Mean | Standard Error | milliseconds (msec) | Baseline and up to 4 hours |
|
|
|
|
| Secondary | Slope of the Placebo-corrected Maximum Heart Rate During Exercise vs. Plasma Concentration of BI 409306 | Slope of the placebo-corrected maximum heart rate during exercise vs. plasma concentration of BI 409306. Patients with available data were included. Exercise testing was completed before gMean Cmax was reached for BI 409306 200 mg arm. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. | The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the ECGS who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups are not mutually exclusive. | Posted | Geometric Mean | 90% Confidence Interval | beats/min | 20 minutes and 2 hours 20 minutes after drug intake |
|
|
|
|
| Secondary | Slope of the Placebo Corrected Change From Maximum Heart Rate 1 and 5 Minutes After End of Exercise and Plasma Concentration | Slope of the placebo-corrected difference between maximum heart rate (HR) during exercise and recovery HR at 1 and 5 minutes (min) after the end of exercise vs. plasma concentration of BI 409306. The note "Not Calculated" represents that the plasma concentrations 1 min after the end of exercise did not reach gMean Cmax for the perticular arm. Patients with available data were included. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. | The pharmacokinetics electrocardiogram set (PKECGS) included all subjects from the ECGS who provided at least 1 valid drug plasma concentration and a corresponding ECG or oxygen variable in any period. Patients in the treatment groups were not mutually exclusive. | Posted | Geometric Mean | 90% Confidence Interval | beats/min | 20 minutes and 2 hours 20 minutes after drug intake |
|
|
|
|
| 0 |
| 20 |
| 4 |
| 20 |
| EG001 | Placebo Under Exercise Conditions | Participants received matching Placebo oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under exercise conditions. | 0 | 20 | 1 | 20 |
| EG002 | BI 409306 50 mg Under Resting Conditions | Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions. | 0 | 20 | 0 | 20 |
| EG003 | BI 409306 50 mg Under Exercise Conditions | Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under exercise conditions. | 0 | 19 | 1 | 19 |
| EG004 | BI 409306 200 mg Under Resting Conditions | Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting conditions. | 0 | 19 | 9 | 19 |
| EG005 | BI 409306 200 mg Under Exercise Conditions | Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under exercise conditions. | 0 | 19 | 7 | 19 |
| Photophobia | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Visual brightness | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Parosmia | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
Not provided
Not provided
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The regression model with response variable placebo-corrected change from max HR to recovery HR (ddHR) and independent variable Plasma concentration includes a fixed slope effect as well as random intercept estimates for each subject (Primary analysis). |
The covariance structure is Unstructured. |
| Slope |
| -0.0029 |
| 2-Sided |
| 95 |
| -0.0052 |
| -0.0007 |
| Superiority or Other (legacy) |