This Study in Healthy Men Tests How Different Doses of BI... | NCT03325712

ID	Type	Description	Link
2017-003269-85	EudraCT Number

Label	Type	Description	Intervention Names
Dose group 1: BI 705564 10 mg	Experimental		Drug: BI 705564
Dose group 2: BI 705564 20 mg	Experimental		Drug: BI 705564 Drug: Midazolam
Dose group 3: BI 705564 40 mg	Experimental		Drug: BI 705564 Drug: Midazolam
Dose group 5: BI 705564 60 mg	Experimental		Drug: BI 705564 Drug: Midazolam
Dose group 4: BI 705564 80 mg	Experimental		Drug: BI 705564 Drug: Midazolam
Placebo matching BI 705564	Placebo Comparator		Drug: Placebo Drug: Midazolam
Dose group 8: BI 705564 40 mg - SPT	Experimental	SPT stands for skin prick test.

Name	Type	Description	Arm Group Labels	Other Names
BI 705564	Drug	Film-coated tablet	Dose group 1: BI 705564 10 mg Dose group 2: BI 705564 20 mg Dose group 3: BI 705564 40 mg Dose group 4: BI 705564 80 mg

Measure	Description	Time Frame
Percentage of Participants With Drug-related Adverse Events	Percentage of participants with drug-related adverse events is reported.	From first drug administration until 10 days after last drug administration, up to 27 days (for dose groups 1 to 5 and "Placebo Matching BI 705564") or up to 37 days (for dose group 8 and "Placebo Matching BI 705564 - SPT").

Measure	Description	Time Frame
Area Under the Concentration-time Curve of BI 705564 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1)	Area under the concentration-time curve of BI 705564 in plasma over a uniform dosing interval τ after administration of the first dose of BI 705564 (AUCτ,1) is reported. Here AUCτ,1 = AUC0-24.	1 hour(s) (h) prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after first BI 705564 dose (for dose groups 1 to 5); 1.5 h prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after first BI 705564 dose (for dose group 8).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Dose Groups (DGs)1 to 5: Healthy male subjects according to the assessment of the investigator, based on a complete medical history, a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests;
DG 8, only: Otherwise healthy male subjects (as defined for DGs 1 to 5) with a history (of at least 1 year) of IgE-mediated, perennial allergies, predominantly to (house) dust mite (dermatophagoides pteronyssinus or dermatophagoides farina) as documented by a positive Skin prick test (SPT)(largest diameter of wheal at screening > 5 mm)
- Age of 18 to 50 years (incl.)
- Body Max 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

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 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
Any evidence of a concomitant disease judged as clinically relevant by the investigator
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Cholecystectomy and/ or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
Diseases of the central nervous system (including but not limited to any kind of seizure 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)
Use of drugs within 30 days prior to administration of trial medication, if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug.
Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
Inability to refrain from smoking on specified trial days
Alcohol abuse (consumption of more than 30 g per day)
Drug abuse or positive drug screening
Blood donation of more than 100 mL within 30 days prior to the administration of trial medication or intended donation during the trial
Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
Inability to comply with dietary regimen of the trial site
A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant Electrocardiogram (ECG) finding at screening
A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

In addition, the following trial-specific exclusion criteria apply:

Male subject with women of child bearing potential (WOCBP) partner who is unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication
Subjects who, in the investigator's judgement, are perceived as having an increased risk of bleeding, e.g. history of haemorrhagic disorders, clinical relevant petechial bleeding, occult blood in faeces, haematuria in repeated urine tests, trauma or surgery within the last month planned surgery during trial participation, history of arteriovenous malformation or aneurysm, history of gastroduodenal ulcer disease or gastrointestinal haemorrhage, history of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding, use of drugs that may interfere with haemostasis during trial conduct (e.g. acetylic salicylic acid or other non-steroidal anti-inflammatory drugs)
Repeated platelet counts below 100 cells/nL at screening
Bleeding times (to monitor platelet function) above reference range at screening
Repeated absolute B cell (CD19+) counts below 40/μL at screening
Serum potassium below normal range at screening
A history or current clinical signs of acute pancreatitis
Further exclusion criteria apply.

Facility	Status	City	State	ZIP	Country	Contacts
CRS Clinical Research Services Mannheim GmbH		Mannheim		68167	Germany

Label	URL
Related Info	View source

ID	Title	Description
FG000	Placebo Matching BI 705564	Participants were orally administered placebo matching to BI 705564 film-coated tablets (and 75 microgram (μg) Midazolam solution for injection, for dose groups 2-5) with 240 milliliter (mL) of water after a standard continental breakfast, on Day 1 and once per day on Days 4 to 17 (for placebo) and on Day -1 and Day 17 (for Midazolam).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 8, 2018	Jul 20, 2022

Arm/Group Information

ID	Title	Description
BG000	Placebo Matching BI 705564	Participants were orally administered placebo matching to BI 705564 film-coated tablets (and 75 microgram (μg) Midazolam solution for injection, for dose groups 2-5) with 240 milliliter (mL) of water after a standard continental breakfast, on Day 1 and once per day on Days 4 to 17 (for placebo) and on Day -1 and Day 17 (for Midazolam).
BG001	Placebo Matching BI 705564 - SPT	Participants with a positive skin prick test (SPT) were orally administered once daily for 28 days placebo matching to BI 705564 film-coated tablets with 240 milliliter (mL) of water after breakfast.
BG002	Dose Group 1: BI 705564 10 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 1 film-coated tablet of 10 milligram (mg) of BI 705564 with 240 milliliter (mL) of water after a standard continental breakfast.
BG003	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
BG004	Dose Group 3: BI 705564 40 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 4 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=40 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
BG005	Dose Group 5: BI 705564 60 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 6 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=60 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
BG006	Dose Group 4: BI 705564 80 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 8 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=80 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (µg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
BG007	Dose Group 8: BI 705564 40 mg - SPT	Participants with a positive skin prick test (SPT) were orally administered for 28 days once daily 4 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=40 mg) with 240 milliliter (mL) of water after breakfast.
BG008	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG0012 BG0028 BG0038 BG0048 BG0058 BG0068 BG0078 BG00860

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

Percentage of Participants With Drug-related Adverse Events

Percentage of participants with drug-related adverse events is reported.

Treated Set (TS): This subject set includes all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.

Posted

Number

Percentage of participants (%)

From first drug administration until 10 days after last drug administration, up to 27 days (for dose groups 1 to 5 and "Placebo Matching BI 705564") or up to 37 days (for dose group 8 and "Placebo Matching BI 705564 - SPT").

ID	Title	Description
OG000	Placebo Matching BI 705564	Participants were orally administered placebo matching to BI 705564 film-coated tablets (and 75 microgram (μg) Midazolam solution for injection, for dose groups 2-5) with 240 milliliter (mL) of water after a standard continental breakfast, on Day 1 and once per day on Days 4 to 17 (for placebo) and on Day -1 and Day 17 (for Midazolam).
OG001	Placebo Matching BI 705564 - SPT	Participants with a positive skin prick test (SPT) were orally administered once daily for 28 days placebo matching to BI 705564 film-coated tablets with 240 milliliter (mL) of water after breakfast.
OG002	Dose Group 1: BI 705564 10 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 1 film-coated tablet of 10 milligram (mg) of BI 705564 with 240 milliliter (mL) of water after a standard continental breakfast.
OG003	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
OG004	Dose Group 3: BI 705564 40 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 4 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=40 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
OG005	Dose Group 5: BI 705564 60 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 6 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=60 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
OG006	Dose Group 4: BI 705564 80 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 8 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=80 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.
OG007	Dose Group 8: BI 705564 40 mg - SPT	Participants with a positive skin prick test (SPT) were orally administered for 28 days once daily 4 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=40 mg) with 240 milliliter (mL) of water after breakfast.

Units	Counts
Participants	OG00010 OG0012 OG0028 OG003

Title

Denominators

Categories

Title	Measurements
	OG00020.0 OG00150.0 OG00212.5 OG003

Secondary

Area Under the Concentration-time Curve of BI 705564 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1)

Area under the concentration-time curve of BI 705564 in plasma over a uniform dosing interval τ after administration of the first dose of BI 705564 (AUCτ,1) is reported. Here AUCτ,1 = AUC0-24.

Pharmacokinetic (PK) parameter analysis set (PKS) included all subjects in the TS who provided at least one PK parameter that was not excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanomole*hour/liter (nmol*h/L)

1 hour(s) (h) prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after first BI 705564 dose (for dose groups 1 to 5); 1.5 h prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after first BI 705564 dose (for dose group 8).

ID	Title	Description
OG000	Dose Group 1: BI 705564 10 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 1 film-coated tablet of 10 milligram (mg) of BI 705564 with 240 milliliter (mL) of water after a standard continental breakfast.
OG001	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.

Secondary

Maximum Measured Concentration of BI 705564 in Plasma (Cmax) After the Administration of the First Dose

Maximum measured concentration of BI 705564 in plasma (Cmax) after the administration of the first dose of BI 705564 is reported.

Pharmacokinetic (PK) parameter analysis set (PKS) included all subjects in the TS who provided at least one PK parameter that was not excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanomole/Liter (nmol/L)

ID	Title	Description
OG000	Dose Group 1: BI 705564 10 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 1 film-coated tablet of 10 milligram (mg) of BI 705564 with 240 milliliter (mL) of water after a standard continental breakfast.
OG001	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (µg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.

Secondary

Area Under the Concentration-time Curve of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After the Administration of the Last Dose

Area under the concentration-time curve of BI 705564 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after the administration of the last dose of BI 705564 is reported.

As per the protocol, day is counted as "Day 1 = 0:00".

Pharmacokinetic (PK) parameter analysis set (PKS) included all subjects in the TS who provided at least one PK parameter that was not excluded. Only participants with evaluable results for this PK parameter are reported.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanomole *hour/liter (nmol*h/L)

1 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after last BI 705564 dose on Day 17 (for dose groups 1 to 5); 1.5 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after last BI 705564 dose on Day 28 (for dose group 8).

ID	Title	Description
OG000	Dose Group 1: BI 705564 10 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 1 film-coated tablet of 10 milligram (mg) of BI 705564 with 240 milliliter (mL) of water after a standard continental breakfast.
OG001	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (µg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.

Secondary

Maximum Measured Concentration of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) After the Administration of the Last Dose

Maximum measured concentration of BI 705564 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after the administration of the last dose.

As per the protocol, day is counted as "Day 1 = 0:00".

Posted

Geometric Mean

Geometric Coefficient of Variation

nanomole/Liter (nmol/L)

ID	Title	Description
OG000	Dose Group 1: BI 705564 10 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 1 film-coated tablet of 10 milligram (mg) of BI 705564 with 240 milliliter (mL) of water after a standard continental breakfast.
OG001	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (µg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.

Secondary

Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) After the First and Last Dose

Area under the concentration-time curve of Midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) after the first and last dose for "Placebo Matching BI 705564" group and for dose groups 2 to 5 is reported.

Pharmacokinetic (PK) parameter analysis set (PKS)-midazolam set (PKS-Mida): This set included all subjects in dose groups 2 to 5 who received midazolam (including placebo-treated subjects). Only participants with evaluable results for this PK parameter are reported.

Posted

Geometric Least Squares Mean

Standard Error

picomole*hour/Liter (pmol*h/L)

1.5 h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after first midazolam dose on Day -1 and 1h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after last midazolam dose on Day 17.

ID	Title	Description
OG000	Placebo Matching BI 705564	Participants were orally administered placebo matching to BI 705564 film-coated tablets (and 75 microgram (μg) Midazolam solution for injection, for dose groups 2-5) with 240 milliliter (mL) of water after a standard continental breakfast, on Day 1 and once per day on Days 4 to 17 (for placebo) and on Day -1 and Day 17 (for Midazolam).
OG001	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (µg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.

Secondary

Maximum Measured Concentration of Midazolam in Plasma (Cmax) After the First and Last Dose

Maximum measured concentration of Midazolam in plasma (Cmax) after the first and last dose for "Placebo Matching BI 705564" group and for dose groups 2 to 5 is reported.

Posted

Geometric Least Squares Mean

Standard Error

picomole/Liter (pmol/L)

ID	Title	Description
OG000	Placebo Matching BI 705564	Participants were orally administered placebo matching to BI 705564 film-coated tablets (and 75 microgram (μg) Midazolam solution for injection, for dose groups 2-5) with 240 milliliter (mL) of water after a standard continental breakfast, on Day 1 and once per day on Days 4 to 17 (for placebo) and on Day -1 and Day 17 (for Midazolam).
OG001	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (µg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Matching BI 705564	Participants were orally administered placebo matching to BI 705564 film-coated tablets (and 75 microgram (μg) Midazolam solution for injection, for dose groups 2-5) with 240 milliliter (mL) of water after a standard continental breakfast, on Day 1 and once per day on Days 4 to 17 (for placebo) and on Day -1 and Day 17 (for Midazolam).	10	10	5	10
EG001	Placebo Matching BI 705564 - SPT	Participants with a positive skin prick test (SPT) were orally administered once daily for 28 days placebo matching to BI 705564 film-coated tablets with 240 milliliter (mL) of water after breakfast.	2	2	2	2
EG002	Dose Group 1: BI 705564 10 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 1 film-coated tablet of 10 milligram (mg) of BI 705564 with 240 milliliter (mL) of water after a standard continental breakfast.	8	8	3	8
EG003	Dose Group 2: BI 705564 20 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 2 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=20 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.	8	8	2	8
EG004	Dose Group 3: BI 705564 40 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 4 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=40 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.	8	8	4	8
EG005	Dose Group 5: BI 705564 60 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 6 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=60 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (μg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.	8	8	5	8
EG006	Dose Group 4: BI 705564 80 mg	Participants were orally administered one single dose on Day 1 and once daily on Days 4 to 17, 8 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=80 mg) with 240 milliliter (mL) of water after a standard continental breakfast. On Day -1 and on Day 17 participants were orally administered also 75 microgram (µg) of solution for injection of midazolam with 240 mL of water after a standard continental breakfast.	8	8	2	8
EG007	Dose Group 8: BI 705564 40 mg - SPT	Participants with a positive skin prick test (SPT) were orally administered for 28 days once daily 4 film-coated tablets of 10 milligram (mg) of BI 705564 (total dosage=40 mg) with 240 milliliter (mL) of water after breakfast.	8	8	7	8

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG0030 affected8 at risk EG0040 affected8 at risk EG0050 affected8 at risk EG0060 affected8 at risk EG0070 affected8 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0021 affected8 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Vessel puncture site haematoma	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Herpes simplex	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected2 at risk EG0020 affected8 at risk EG003
Dizziness	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected2 at risk EG0022 affected8 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Orthostatic intolerance	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Sciatica	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003
Haematoma	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected2 at risk EG0020 affected8 at risk EG003

ID	Term
D001569	Benzodiazepines
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds