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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-005721-67 | EudraCT Number | EudraCT |
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To investigate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of single rising doses of BI 691751 in healthy male subjects (part I).
To investigate the relative bioavailability of BI 691751 given as tablet versus oral solution (part II)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 691751 dose 2 (part I) | Experimental | single dose given as oral solution |
|
| BI 691751 dose 3 (part I) | Experimental | single dose given as oral solution |
|
| BI 691751 dose 4 (part I) | Experimental | single dose given as oral solution |
|
| BI 691751 dose 5 (part I) | Experimental | single dose given as oral solution |
|
| BI 691751 dose 6 (part I) | Experimental | single dose given as oral solution |
|
| BI 691751 dose 7 (part I) | Experimental | single dose given as oral solution |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 691751 | Drug | oral solution BI 691751, dose 6 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-72h (Part II) | AUC0-72h (area under the concentration-time curve of the analyte of BI 691751 in plasma over the time interval from 0 to 72 h) (part II). PPS-BA included all subjects in the TS who were randomised to the BA part, who provided at least one observation for at least one primary endpoint, had no important protocol violations relevant for the statistical evaluation of BA and did not experience emesis at or before twice the median tmax. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h and 72h after drug administration |
| Cmax (Part II) | Cmax (maximum measured concentration of the analyte of BI 691751 in plasma) (part II) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug administration |
| Frequency of Subjects With Drug-related Adverse Events (Part I) | Frequency of subjects with drug-related Adverse Events (AEs) (Part I) | Part I: 'Day1 to Day21 for Dose 1, 2,3 &4 and Day1 to Day45 for Dose group 5,6 & 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax (Part I) | Cmax (maximum measured concentration of BI 691751 in plasma) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin |
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Inclusion criteria:
Exclusion criteria:
1. Any relevant deviation from healthy conditions
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1334.1.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (Part I) | placebo solution Placebo: placebo solution |
| FG001 | BI 691751 Dose 1 (Part I) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) |
| FG002 | BI 691751 Dose 2 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) |
| FG003 | BI 691751 Dose 3 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) |
| FG004 | BI 691751 Dose 4 (Part I) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) |
| FG005 | BI 691751 Dose 5 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) |
| FG006 | BI 691751 Dose 6 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) |
| FG007 | BI 691751 Dose 7 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) |
| FG008 | BI 691751 Tablet (Part II) | single dose given as 1 tablet BI 691751: 1 tablet (10 mg) |
| FG009 | BI 691751 Solution (Part II); Extensive Metabolizers | single dose given as oral solution BI 691751: oral solution (10 mg) 5 subjects had no measurable concentration of BI 691751 because a drug-free solution has been administered by mistake. Therefore their results were excluded from all analyses. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated Set (TS): includes all subjects who were documented to have taken at least 1 dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo (Part I) | placebo solution Placebo: placebo solution |
| BG001 | BI 691751dose 1 (Part I) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | AUC0-72h (Part II) | AUC0-72h (area under the concentration-time curve of the analyte of BI 691751 in plasma over the time interval from 0 to 72 h) (part II). PPS-BA included all subjects in the TS who were randomised to the BA part, who provided at least one observation for at least one primary endpoint, had no important protocol violations relevant for the statistical evaluation of BA and did not experience emesis at or before twice the median tmax. | Per protocol set for evaluation of bioavailability (PPS-BA). Only subjects with calculable PK parameter were analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h and 72h after drug administration |
|
Day1 to Day21 for Dose group 1, 2,3 & 4 and Day1 to Day45 for Dose group 5,6 & 7. Part II: Day1 to Day 45.
Subjects randomised to 0.5 mg sol. or 1.5 mg sol. were planned by the CTP to be observed for 8 to 21 days, subjects randomised to 5 mg sol. or 15 mg sol. for 11 to 21 days, and subjects randomised to 10 mg sol., 10 mg tab., 30 mg sol., 60 mg sol., or 90 mg sol. for 31 to 45 days after treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (Part I) | placebo solution Placebo: placebo solution |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Contusion | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| BI 691751dose 1 (part I) | Experimental | single dose given as oral solution |
|
| Placebo (part I) | Placebo Comparator | placebo solution |
|
| BI 691751 tablet (part II) | Experimental | single dose given as 1 tablet |
|
| BI 691751 solution (part II) | Active Comparator | single dose given as oral solution |
|
| BI 691751 |
| Drug |
oral solution |
|
| Placebo | Drug | placebo solution |
|
| BI 691751 | Drug | oral solution BI 691751, dose 2 |
|
| BI 691751 | Drug | oral solution BI 691751, dose 5 |
|
| BI 691751 | Drug | 1 tablet |
|
| BI 691751 | Drug | oral solution BI 691751, dose 3 |
|
| BI 691751 | Drug | oral solution BI 69175, dose 4 |
|
| BI 691751 | Drug | oral solution BI 691751, dose 7 |
|
| BI 691751 | Drug | oral solution BI 69175, dose 1 |
|
| for dose 1 & 2: up to 168h, for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
| AUC0-infinity (Part I) | AUC0-infinity (area under the concentration-time curve of BI 691751 in plasma over the time interval from 0 extrapolated to infinity) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
| AUC0-tz | AUC0-tz (area under the concentration-time curve of BI 691751 in plasma over the time interval from 0 up to the last quantifiable data point) (Part I and Part II) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | Part 1: for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 7: up to 720h; Part 2: up to 720h |
| t1/2 (Part I) | t1/2 (terminal half-life of the analyte of BI 691751 in plasma) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
| Tmax (Part I) | tmax (time from dosing to maximum measured concentration of BI 691751) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
| BG002 | BI 691751 Dose 2 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) |
| BG003 | BI 691751 Dose 3 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) |
| BG004 | BI 691751 Dose 4 (Part I) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) |
| BG005 | BI 691751 Dose 5 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) |
| BG006 | BI 691751 Dose 6 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) |
| BG007 | BI 691751 Dose 7 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) |
| BG008 | BI 691751 Tablet (Part II) | single dose given as 1 tablet BI 691751: 1 tablet (10 mg) |
| BG009 | BI 691751 Solution (Part II); Extensive Metabolizers | single dose given as oral solution BI 691751: oral solution (10 mg) 5 subjects had no measurable concentration of BI 691751 because a drug-free solution has been administered by mistake. Therefore their results were excluded from all analyses. |
| BG010 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | BI 691751 Tablet Poor Metabolizers (Part II) | single dose given as 1 tablet; poor metabolizers; BI 691751: 1 tablet (10 mg) |
| OG002 | BI 691751 Solution (Part II); Extensive Metabolizers | single dose given as oral solution BI 691751: oral solution (10 mg) 5 subjects had no measurable concentration of BI 691751 because a drug-free solution has been administered by mistake. Therefore their results were excluded from all analyses. |
|
|
|
| Primary | Cmax (Part II) | Cmax (maximum measured concentration of the analyte of BI 691751 in plasma) (part II) | PPS-BA. Only subjects with calculable PK parameter were analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug administration |
|
|
|
|
| Secondary | Cmax (Part I) | Cmax (maximum measured concentration of BI 691751 in plasma) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | Per protocol set for evaluation of dose proportionality (PPS-DP): This subject set includes all subjects of the TS who were randomised to active treatment in the single rising dose part or BA part, and had no important PVs relevant for the statistical evaluation of dose proportionality. Only subjects with calculable PK parameter were analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | for dose 1 & 2: up to 168h, for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
|
|
|
|
| Secondary | AUC0-infinity (Part I) | AUC0-infinity (area under the concentration-time curve of BI 691751 in plasma over the time interval from 0 extrapolated to infinity) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | PPS-DP. Only subjects with calculable PK parameter were analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
|
|
|
|
| Secondary | AUC0-tz | AUC0-tz (area under the concentration-time curve of BI 691751 in plasma over the time interval from 0 up to the last quantifiable data point) (Part I and Part II) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | PPS-DP for part I and PPS-BA for part II. Only subjects with calculable PK parameter were analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | Part 1: for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 7: up to 720h; Part 2: up to 720h |
|
|
|
|
| Secondary | t1/2 (Part I) | t1/2 (terminal half-life of the analyte of BI 691751 in plasma) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | Pharmacokinetic (PK) set (PKS) which includes all subjects of the treated set were were randomised to active treatment in the single rising dose part of bioavailability part, and had no important protocol violations relevant for the statistical evaluation of further PK parameters. Only subjects with calculable PK parameter were analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
|
|
|
| Secondary | Tmax (Part I) | tmax (time from dosing to maximum measured concentration of BI 691751) (part I) Time frame: Dose 1 and 2: 1 hour (h) before drug administration (admin) and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h and 168h after drug admin Dose 3 and 4: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h (dose group 4 only), 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h and 240h after drug admin Dose 5 to 7: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 336h, 432h, 528h, 624h and 720h after drug admin Dose 8: 1h before drug admin and 20 min, 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 216h, 384h, 552h and 720h after drug admin | PKS | Posted | Median | Full Range | h | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
|
|
|
| Primary | Frequency of Subjects With Drug-related Adverse Events (Part I) | Frequency of subjects with drug-related Adverse Events (AEs) (Part I) | Treated Set (TS): all subjects who were documented to have taken at least 1 dose of study medication. | Posted | Number | Participants | Part I: 'Day1 to Day21 for Dose 1, 2,3 &4 and Day1 to Day45 for Dose group 5,6 & 7 |
|
|
|
| 0 |
| 13 |
| 5 |
| 13 |
| EG001 | BI 691751 Dose 1 (Part I) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | 0 | 6 | 1 | 6 |
| EG002 | BI 691751 Dose 2 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | 0 | 5 | 2 | 5 |
| EG003 | BI 691751 Dose 3 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | 0 | 6 | 2 | 6 |
| EG004 | BI 691751 Dose 4 (Part I) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | 0 | 6 | 2 | 6 |
| EG005 | BI 691751 Dose 5 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | 0 | 6 | 1 | 6 |
| EG006 | BI 691751 Dose 6 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | 0 | 5 | 3 | 5 |
| EG007 | BI 691751 Dose 7 (Part I) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | 0 | 5 | 4 | 5 |
| EG008 | BI 691751 Tablet (Part II) | single dose given as 1 tablet BI 691751: 1 tablet (10 mg) | 0 | 17 | 5 | 17 |
| EG009 | BI 691751 Solution (Part II); Extensive Metabolizers | single dose given as oral solution BI 691751: oral solution (10 mg) 5 subjects had no measurable concentration of BI 691751 because a drug-free solution has been administered by mistake. Therefore their results were excluded from all analyses. | 1 | 12 | 3 | 12 |
| Nasopharyngitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Eye irritation | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Arthropod sting | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
|
Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Comparison of poor metabolisers (5 (all) subjects of group 'BI 691751 tablet poor metabolizers (part II)') and extensive metabolisers (12 (all) subjects of group 'BI 691751 tablet extensive metabolizers (part II)'). | ANOVA | Geometric mean ratio (net) | 92.69 | Standard Deviation | 33.0 | 2-Sided | 90 | 68.662 | 125.119 | The geometric mean ratio was calculated as the geometric mean of the poor metabolisers divided by the geometric mean of the extensive metabolisers. | No | Superiority or Other |
| Comparison of poor metabolisers (5 (all) subjects of group 'BI 691751 tablet poor metabolizers (part II)') and extensive metabolisers (12 (all) subjects of group 'BI 691751 tablet extensive metabolizers (part II)'). | ANOVA | Geometric mean ratio (net) | 109.80 | Standard Deviation | 28.8 | 2-Sided | 90 | 84.376 | 142.894 | The geometric mean ratio was calculated as the geometric mean of the poor metabolisers divided by the geometric mean of the extensive metabolisers. | No | Superiority or Other |
| Regression, Linear | Slope | 1.0312 | 2-Sided | 95 | 0.833 | 1.1790 | Yes | Non-Inferiority or Equivalence | This was non-confirmatory testing. |