Safety and Pharmacokinetics of Single Rising Doses of BI 705564 and Food Effect on BI 705564 in Healthy Male Subjects
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT03123185
Collaborator
(none)
91
1
14
9.8
9.3
Study Details
Study Description
Brief Summary
Investigation of safety, tolerability, pharmacokinetics and pharmacodynamics of single rising doses of BI 705564 and of the food effect on BI 705564 in healthy male subjects
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The primary objective of the single rising dose part under fasting and under fed conditions is to investigate safety and tolerability of BI 705564 in healthy male subjects following oral administration of single rising doses.
Secondary objectives are the exploration of pharmacokinetics (PK) including dose proportionality, and pharmacodynamics (PD) of BI 705564 after single rising doses.
The objective of the food effect part is to explore the relative bioavailability of BI 705564 tablets under fed and fasted conditions following the oral administration of single doses.
Study Design
Study Type:
Interventional
Actual Enrollment
:
91 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 705564 (Single-blind, Partially Randomised, Placebo-controlled Parallel Group Design) and Food Effect on a Tablet Formulation of BI 705564 (Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Design) in Healthy Male Subjects
Actual Study Start Date
:
Apr 27, 2017
Actual Primary Completion Date
:
Feb 19, 2018
Actual Study Completion Date
:
Feb 19, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Placebo matching BI 705564 fasted (SRD part)
|
Drug: Placebo
Tablet and solution formulation
|
| Experimental: Placebo matching BI 705564 fed (SRD part)
|
Drug: Placebo
Tablet and solution formulation
|
| Experimental: 1 milligram (mg) BI 705564 fasted (SRD part)
|
Drug: BI 705564 (Reference)
Fasting state
|
| Experimental: 3 mg BI 705564 fasted (SRD part)
|
Drug: BI 705564 (Reference)
Fasting state
|
| Experimental: 10 mg BI 705564 fasted (SRD part)
|
Drug: BI 705564 (Reference)
Fasting state
|
| Experimental: 20 mg BI 705564 fasted (SRD part)
|
Drug: BI 705564 (Reference)
Fasting state
|
| Experimental: 40 mg BI 705564 fasted (SRD part)
|
Drug: BI 705564 (Reference)
Fasting state
|
| Experimental: 80 mg BI 705564 fasted (SRD part)
|
Drug: BI 705564 (Reference)
Fasting state
|
| Experimental: 20 mg BI 705564 fed (SRD part)
|
Drug: BI 705564 (Test)
Fed state
|
| Experimental: 40 mg BI 705564 fed (SRD part)
|
Drug: BI 705564 (Test)
Fed state
|
| Experimental: 80 mg BI 705564 fed (SRD part)
|
Drug: BI 705564 (Test)
Fed state
|
| Experimental: 160 mg BI 705564 fed (SRD part)
|
Drug: BI 705564 (Test)
Fed state
|
| Experimental: BI 705564 10 mg fasted/ BI 705564 10 mg fed (FE Part)
|
Drug: BI 705564 (Test)
Fed state
Drug: BI 705564 (Reference)
Fasting state
|
| Experimental: BI 705564 10 mg fed/ BI 705564 10 mg fasted (FE Part)
|
Drug: BI 705564 (Test)
Fed state
Drug: BI 705564 (Reference)
Fasting state
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Drug-related Adverse Events (AEs) [From drug administration until end of the treatment, up to 15 days (for SRD fasting and fed conditions).]
Number of participants with drug-related adverse events (AEs) is presented for SRD part.Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported. Percentages are calculated using total number of subjects per treatment as the denominator.
- Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (FE Part) [Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.]
AUC0-tz, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 to the last quantifiable data point for FE part is presented.
- Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (FE Part) [Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.]
Cmax, maximum measured concentration of BI 705564 in plasma is presented for FE part.
Secondary Outcome Measures
- Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) [Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.]
Cmax, maximum measured concentration of BI 705564 in plasma is presented for SRD part.
- Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) [Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.]
AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity is presented for SRD part.
- Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (FE Part) [Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.]
AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 50 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Healthy male 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 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
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 140mmHg, 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 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)
-
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 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 the 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 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 subjects with women of childbearing potential [WOCBP] partner who are 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
-
Repeated absolute B cell (CD19+) counts below 40/μL at screening
-
Repeated platelet counts below 100 cells/nL at screening
-
Serum potassium below normal range at screening
-
A history or current clinical signs of acute pancreatitis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Humanpharmakologisches Zentrum Biberach | Biberach | Germany | 88397 |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT03123185
Other Study ID Numbers:
- 1408-0001
- 2017-000324-98
First Posted:
Apr 21, 2017
Last Update Posted:
Jul 6, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Study Results
Participant Flow
| Recruitment Details | This was a study in healthy men to test how different doses of BI 705564 are taken up in the body and whether taking BI 705564 with food makes a difference. The single rising dose (SRD) parts under fasting and fed conditions were designed as partially randomised within dose groups, placebo-controlled, single-blind, parallel-group design. The food effect (FE) part was designed as open-label, randomised, single-dose, two-period, two-sequence crossover design. |
|---|---|
| Pre-assignment Detail | All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met. For the food effect part: Single dose for each treatment (2 single doses in total) were separated by a washout period of at least 10 days |
| Arm/Group Title | Placebo Matching BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) | BI 705564 10 mg Fasted/ BI 705564 10 mg Fed (FE Part) | BI 705564 10 mg Fed/BI 705564 10 mg Fasted (FE Part) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered single dose of placebo matching BI 705564 orally as powder for oral solution or film-coated tablet with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). | Participants were administered single dose of placebo matching BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered a single dose of 1 mg BI 705564 (4 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered a single dose of 3 mg BI 705564 (12 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x100 mg and 6x10 mg (160 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet after an overnight fast of at least 10 h in period 1 (fast condition), with 240 milliliters (mL) of water. Followed by single dose of 1x10 mg (10 mg) BI 705564 after a high-fat, high-calorie meal in period 2 (fed condition). Both treatments were separated by a washout period of at least 10 days. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet after a high-fat, high-calorie meal in period 1 (fed condition), with 240 milliliters (mL) of water. Followed by single dose of 1x10 mg (10 mg) BI 705564 after an overnight fast of at least 10 h in period 2 (fast condition). Both treatments were separated by a washout period of at least 10 days. |
| Period Title: Overall Study | ||||||||||||||
| STARTED | 12 | 8 | 6 | 5 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| COMPLETED | 12 | 8 | 6 | 5 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo Matching BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) | BI 705564 10 mg Fasted/ BI 705564 10 mg Fed (FE Part) | BI 705564 10 mg Fed/BI 705564 10 mg Fasted (FE Part) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered single dose of placebo matching BI 705564 orally as powder for oral solution or film-coated tablet with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). | Participants were administered single dose of placebo matching BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered a single dose of 1 mg BI 705564 (4 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered a single dose of 3 mg BI 705564 (12 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x100 mg and 6x10 mg (160 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet after an overnight fast of at least 10 h in period 1 (fast condition), with 240 milliliters (mL) of water. Followed by single dose of 1x10 mg (10 mg) BI 705564 after a high-fat, high-calorie meal in period 2 (fed condition). Both treatments were separated by a washout period of at least 10 days. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet after a high-fat, high-calorie meal in period 1 (fed condition), with 240 milliliters (mL) of water. Followed by single dose of 1x10 mg (10 mg) BI 705564 after an overnight fast of at least 10 h in period 2 (fast condition). Both treatments were separated by a washout period of at least 10 days. | Total of all reporting groups |
| Overall Participants | 12 | 8 | 6 | 5 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 91 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||||||||
| Mean (Standard Deviation) [Years] |
35.3
(9.6)
|
39.1
(6.1)
|
36.0
(5.2)
|
29.6
(8.4)
|
32.5
(8.2)
|
33.3
(9.3)
|
36.8
(8.6)
|
35.3
(8.6)
|
37.7
(8.8)
|
30.2
(6.7)
|
33.8
(7.9)
|
38.7
(7.6)
|
29.3
(10.2)
|
34.2
(12.2)
|
34.5
(8.5)
|
| Sex: Female, Male (Count of Participants) | |||||||||||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
12
100%
|
8
100%
|
6
100%
|
5
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
91
100%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
12
100%
|
8
100%
|
6
100%
|
5
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
91
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Participants With Drug-related Adverse Events (AEs) |
|---|---|
| Description | Number of participants with drug-related adverse events (AEs) is presented for SRD part.Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported. Percentages are calculated using total number of subjects per treatment as the denominator. |
| Time Frame | From drug administration until end of the treatment, up to 15 days (for SRD fasting and fed conditions). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): TS included all subjects who were dispensed trial medication and were documented to have taken at least 1 dose of the investigational treatment. |
| Arm/Group Title | Placebo Matching BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) | Placebo Matching BI 705564 Total | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | Total BI 705564 Fast (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) | Total BI 705564 Fed (SRD Part) | Total BI 705564 (SRD Part) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered single dose of placebo matching BI 705564 orally as powder for oral solution or film-coated tablet with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). | Participants were administered single dose of placebo matching BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of placebo matching BI 705564 orally as powder for oral solution or film-coated tablet with 240 milliliters (mL) of water after an overnight fast of at least 10 h in fast condition or after a high-fat, high-calorie meal in fed condition. | Participants were administered a single dose of 1 mg BI 705564 (4 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered a single dose of 3 mg BI 705564 (12 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of BI 705564 orally as powder for oral solution or film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x100 mg and 6x10 mg (160 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal | Participants were administered single dose of BI 705564 orally as powder for oral solution or film-coated tablet with 240 mL of water as after an overnight fast of at least 10 h in fast condition or after a high-fat, high-calorie meal in fed condition. |
| Measure Participants | 12 | 8 | 20 | 6 | 5 | 6 | 6 | 6 | 6 | 35 | 6 | 6 | 6 | 6 | 24 | 59 |
| Count of Participants [Participants] |
3
25%
|
1
12.5%
|
4
66.7%
|
1
20%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
3
50%
|
0
0%
|
4
66.7%
|
0
0%
|
0
0%
|
4
4.4%
|
7
NaN
|
| Title | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (FE Part) |
|---|---|
| Description | AUC0-tz, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 to the last quantifiable data point for FE part is presented. |
| Time Frame | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability. |
| Arm/Group Title | 10 mg BI 705564 Fed (FE Part) | 10 mg BI 705564 Fast (FE Part) |
|---|---|---|
| Arm/Group Description | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. |
| Measure Participants | 11 | 12 |
| Least Squares Mean (Standard Error) [nanomole*hour/litre [nmol*h/L]] |
NA
(NA)
|
NA
(NA)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Matching BI 705564 Fasted (SRD Part), Placebo Matching BI 705564 Fed (SRD Part) |
|---|---|---|
| Comments | The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect "subjects within sequences" will be considered as random, the other effects as fixed. | |
| Type of Statistical Test | Other | |
| Comments | No hypothesis was tested and no acceptance range was specified. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean (gMean) ratio (%) |
| Estimated Value | 158.61 | |
| Confidence Interval |
(2-Sided) 90% 133.679 to 188.195 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 22.4 |
|
| Estimation Comments | gMean ratio = 10 mg BI 705564 fed/10 mg BI 705564 fast. Standard Error of the mean is actually the intra-individual geometric coefficient variation. | |
| Title | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (FE Part) |
|---|---|
| Description | Cmax, maximum measured concentration of BI 705564 in plasma is presented for FE part. |
| Time Frame | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability. |
| Arm/Group Title | 10 mg BI 705564 Fed (FE Part) | 10 mg BI 705564 Fast (FE Part) |
|---|---|---|
| Arm/Group Description | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. |
| Measure Participants | 11 | 12 |
| Least Squares Mean (Standard Error) [Nanomole/litre [nmol/L]] |
NA
(NA)
|
NA
(NA)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Matching BI 705564 Fasted (SRD Part), Placebo Matching BI 705564 Fed (SRD Part) |
|---|---|---|
| Comments | The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect "subjects within sequences" will be considered as random, the other effects as fixed. | |
| Type of Statistical Test | Other | |
| Comments | No hypothesis was tested and no acceptance range was specified. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio (%) |
| Estimated Value | 194.18 | |
| Confidence Interval |
(2-Sided) 90% 158.912 to 237.267 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 26.4 |
|
| Estimation Comments | gMean ratio = 10 mg BI 705564 fed/10 mg BI 705564 fast. Standard Error of the mean is actually the intra-individual geometric coefficient variation. | |
| Title | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) |
|---|---|
| Description | Cmax, maximum measured concentration of BI 705564 in plasma is presented for SRD part. |
| Time Frame | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability. |
| Arm/Group Title | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered a single dose of 1 mg BI 705564 (4 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered a single dose of 3 mg BI 705564 (12 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x100 mg and 6x10 mg (160 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. |
| Measure Participants | 6 | 5 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Nanomole/litre [nmol/L]] |
1.66
(26.9)
|
7.51
(34.9)
|
4.94
(25.9)
|
12.9
(55.5)
|
14.5
(40.7)
|
16.5
(29.3)
|
23.9
(17.0)
|
41.2
(36.0)
|
58.3
(12.1)
|
122.0
(58.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo Matching BI 705564 Fasted (SRD Part), Placebo Matching BI 705564 Fed (SRD Part), Placebo Matching BI 705564 Total, 1 Milligram (mg) BI 705564 Fasted (SRD Part), 3 mg BI 705564 Fasted (SRD Part), 10 mg BI 705564 Fasted (SRD Part) |
|---|---|---|
| Comments | The basic model for the investigation of dose proportionality for fasted condition was a power model that describes the functional relationship between the dose and PK endpoints. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.4879 | |
| Confidence Interval |
(2-Sided) 95% 0.3767 to 0.5990 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0546 |
|
| Estimation Comments | Based on the estimate for slope parameter, a 2-sided 95% Confidence Interval (CI) for the slope was computed. Standard error of the mean is actually standard error of slope. Perfect dose proportionality would correspond to a slope of 1. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 20 mg BI 705564 Fasted (SRD Part), 40 mg BI 705564 Fasted (SRD Part), 80 mg BI 705564 Fasted (SRD Part), Total BI 705564 Fast (SRD Part) |
|---|---|---|
| Comments | The basic model for the investigation of dose proportionality for fed condition was a power model that describes the functional relationship between the dose and PK endpoints. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.7553 | |
| Confidence Interval |
(2-Sided) 95% 0.5736 to 0.9370 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0876 |
|
| Estimation Comments | Based on the estimate for slope parameter, a 2-sided 95% CI for the slope was computed. Standard error of the mean is actually standard error of slope. Perfect dose proportionality would correspond to a slope of 1. | |
| Title | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) |
|---|---|
| Description | AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity is presented for SRD part. |
| Time Frame | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability. |
| Arm/Group Title | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered a single dose of 1 mg BI 705564 (4 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered a single dose of 3 mg BI 705564 (12 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x100 mg and 6x10 mg (160 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. |
| Measure Participants | 6 | 5 | 6 | 5 | 5 | 6 | 6 | 4 | 5 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nanomole*hour/litre [nmol*h/L]] |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
54.0
(29.7)
|
74.2
(37.4)
|
98.1
(43.4)
|
NA
(NA)
|
185.0
(35.5)
|
330.0
(31.2)
|
481.0
(48.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 Milligram (mg) BI 705564 Fasted (SRD Part), 3 mg BI 705564 Fasted (SRD Part), 10 mg BI 705564 Fasted (SRD Part) |
|---|---|---|
| Comments | The basic model for the investigation of dose proportionality for fasted condition was a power model that describes the functional relationship between the dose and PK endpoints. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.4651 | |
| Confidence Interval |
(2-Sided) 95% 0.1935 to 0.7368 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1274 |
|
| Estimation Comments | Based on the estimate for slope parameter, a 2-sided 95% CI for the slope was computed. Standard error of the mean is actually standard error of slope. Perfect dose proportionality would correspond to a slope of 1. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 40 mg BI 705564 Fasted (SRD Part), 80 mg BI 705564 Fasted (SRD Part), Total BI 705564 Fast (SRD Part) |
|---|---|---|
| Comments | The basic model for the investigation of dose proportionality for fed condition was a power model that describes the functional relationship between the dose and PK endpoints. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.6651 | |
| Confidence Interval |
(2-Sided) 95% 0.3679 to 0.9622 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1385 |
|
| Estimation Comments | Based on the estimate for slope parameter, a 2-sided 95% CI for the slope was computed. Standard error of the mean is actually standard error of slope. Perfect dose proportionality would correspond to a slope of 1. | |
| Title | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (FE Part) |
|---|---|
| Description | AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity. |
| Time Frame | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS: Only participants with evaluable results for this PK parameter are reported. |
| Arm/Group Title | 10 mg BI 705564 Fed (FE Part) | 10 mg BI 705564 Fast (FE Part) |
|---|---|---|
| Arm/Group Description | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. |
| Measure Participants | 0 | 2 |
| Geometric Mean (Geometric Coefficient of Variation) [nanomole*hour/litre [nmol*h/L]] |
NA
(NA)
|
Adverse Events
| Time Frame | From drug administration until end of the treatment, up to 15 days (for SRD part fasting and fed condition and FE part). | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||||||||||
| Arm/Group Title | Placebo Matching BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) | Placebo Matching BI 705564 Total | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | Total BI 705564 Fast (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) | Total BI 705564 Fed (SRD Part) | Total BI 705564 (SRD Part) | 10 mg BI 705564 Fast (FE Part) | 10 mg BI 705564 Fed (FE Part) | ||||||||||||||||||
| Arm/Group Description | Participants were administered single dose of placebo matching BI 705564 orally as powder for oral solution or film-coated tablet with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). | Participants were administered single dose of placebo matching BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of placebo matching BI 705564 orally as powder for oral solution or film-coated tablet with 240 milliliters (mL) of water after an overnight fast of at least 10 h in fast condition or after a high-fat, high-calorie meal in fed condition. | Participants were administered a single dose of 1 mg BI 705564 (4 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered a single dose of 3 mg BI 705564 (12 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of BI 705564 orally as powder for oral solution or film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of 1x100 mg and 6x10 mg (160 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | Participants were administered single dose of BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal | Participants were administered single dose of BI 705564 orally as powder for oral solution or film-coated tablet with 240 mL of water as after an overnight fast of at least 10 h in fast condition or after a high-fat, high-calorie meal in fed condition. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | ||||||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||||||||
| Placebo Matching BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) | Placebo Matching BI 705564 Total | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | Total BI 705564 Fast (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) | Total BI 705564 Fed (SRD Part) | Total BI 705564 (SRD Part) | 10 mg BI 705564 Fast (FE Part) | 10 mg BI 705564 Fed (FE Part) | |||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||||||||||
| Placebo Matching BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) | Placebo Matching BI 705564 Total | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | Total BI 705564 Fast (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) | Total BI 705564 Fed (SRD Part) | Total BI 705564 (SRD Part) | 10 mg BI 705564 Fast (FE Part) | 10 mg BI 705564 Fed (FE Part) | |||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||||||||||
| Placebo Matching BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) | Placebo Matching BI 705564 Total | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | Total BI 705564 Fast (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 160 mg BI 705564 Fed (SRD Part) | Total BI 705564 Fed (SRD Part) | Total BI 705564 (SRD Part) | 10 mg BI 705564 Fast (FE Part) | 10 mg BI 705564 Fed (FE Part) | |||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/12 (50%) | 3/8 (37.5%) | 9/20 (45%) | 3/6 (50%) | 1/5 (20%) | 2/6 (33.3%) | 1/6 (16.7%) | 3/6 (50%) | 2/6 (33.3%) | 12/35 (34.3%) | 3/6 (50%) | 4/6 (66.7%) | 0/6 (0%) | 3/6 (50%) | 10/24 (41.7%) | 22/59 (37.3%) | 2/12 (16.7%) | 2/11 (18.2%) | ||||||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||
| Palpitations | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 1/11 (9.1%) | ||||||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||
| Abdominal pain | 1/12 (8.3%) | 0/8 (0%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Abdominal pain upper | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 1/11 (9.1%) | ||||||||||||||||||
| Aphthous ulcer | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/24 (4.2%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Diarrhoea | 0/12 (0%) | 1/8 (12.5%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/24 (4.2%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Nausea | 0/12 (0%) | 1/8 (12.5%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/35 (2.9%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/24 (4.2%) | 2/59 (3.4%) | 0/12 (0%) | 1/11 (9.1%) | ||||||||||||||||||
| Vomiting | 0/12 (0%) | 1/8 (12.5%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/24 (4.2%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| General disorders | ||||||||||||||||||||||||||||||||||||
| Chest pain | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/35 (2.9%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 1/59 (1.7%) | 0/12 (0%) | 1/11 (9.1%) | ||||||||||||||||||
| Vessel puncture site swelling | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 1/12 (8.3%) | 0/11 (0%) | ||||||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||
| Nasopharyngitis | 0/12 (0%) | 1/8 (12.5%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/24 (4.2%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Oral herpes | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/24 (4.2%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Rhinitis | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/24 (4.2%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||
| Arthropod sting | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/35 (2.9%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Scratch | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/35 (2.9%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Skin abrasion | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 1/11 (9.1%) | ||||||||||||||||||
| Thermal burn | 0/12 (0%) | 1/8 (12.5%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||
| Dizziness | 0/12 (0%) | 1/8 (12.5%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Headache | 3/12 (25%) | 1/8 (12.5%) | 4/20 (20%) | 2/6 (33.3%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 5/35 (14.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 3/24 (12.5%) | 8/59 (13.6%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||
| Oropharyngeal pain | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/35 (2.9%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/24 (4.2%) | 2/59 (3.4%) | 1/12 (8.3%) | 0/11 (0%) | ||||||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||
| Erythema | 1/12 (8.3%) | 0/8 (0%) | 1/20 (5%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/35 (2.9%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Rash | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 1/11 (9.1%) | ||||||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||||||||||
| Haematoma | 1/12 (8.3%) | 0/8 (0%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 2/35 (5.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/24 (4.2%) | 3/59 (5.1%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Hot flush | 1/12 (8.3%) | 0/8 (0%) | 1/20 (5%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/35 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 0/59 (0%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
| Thrombophlebitis | 0/12 (0%) | 0/8 (0%) | 0/20 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/35 (2.9%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/24 (0%) | 1/59 (1.7%) | 0/12 (0%) | 0/11 (0%) | ||||||||||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Boehringer Ingelheim, Call Center |
|---|---|
| Organization | Boehringer Ingelheim |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT03123185
Other Study ID Numbers:
- 1408-0001
- 2017-000324-98
First Posted:
Apr 21, 2017
Last Update Posted:
Jul 6, 2022
Last Verified:
Mar 1, 2022