Safety of Single Rising Doses and Relative Bioavailability of BI 691751
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT01843972
Collaborator
(none)
81
1
10
7
11.5
Study Details
Study Description
Brief Summary
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
81 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single
Primary Purpose:
Treatment
Official Title:
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising Oral Doses of BI 691751 in Healthy Male Volunteers in a Randomised, Single-blind, Placebo-controlled Design (Part I) and Investigation of Relative Bioavailability of BI 691751 Given as Tablet and Oral Solution to Healthy Male Subjects in an Open, Randomised, Single-dose, Single Period Parallel Group Design (Part II).
Study Start Date
:
Apr 1, 2013
Actual Primary Completion Date
:
Nov 1, 2013
Actual Study Completion Date
:
Nov 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BI 691751 dose 2 (part I) single dose given as oral solution |
Drug: BI 691751
oral solution BI 691751, dose 2
|
| Experimental: BI 691751 dose 3 (part I) single dose given as oral solution |
Drug: BI 691751
oral solution BI 691751, dose 3
|
| Experimental: BI 691751 dose 4 (part I) single dose given as oral solution |
Drug: BI 691751
oral solution BI 69175, dose 4
|
| Experimental: BI 691751 dose 5 (part I) single dose given as oral solution |
Drug: BI 691751
oral solution BI 691751, dose 5
|
| Experimental: BI 691751 dose 6 (part I) single dose given as oral solution |
Drug: BI 691751
oral solution BI 691751, dose 6
|
| Experimental: BI 691751 dose 7 (part I) single dose given as oral solution |
Drug: BI 691751
oral solution BI 691751, dose 7
|
| Experimental: BI 691751dose 1 (part I) single dose given as oral solution |
Drug: BI 691751
oral solution BI 69175, dose 1
|
| Placebo Comparator: Placebo (part I) placebo solution |
Drug: Placebo
placebo solution
|
| Experimental: BI 691751 tablet (part II) single dose given as 1 tablet |
Drug: BI 691751
1 tablet
|
| Active Comparator: BI 691751 solution (part II) single dose given as oral solution |
Drug: BI 691751
oral solution
|
Outcome Measures
Primary Outcome Measures
- AUC0-72h (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 and 72h after drug administration]
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.
- Cmax (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]
Cmax (maximum measured concentration of the analyte of BI 691751 in plasma) (part II)
- Frequency of Subjects With Drug-related Adverse Events (Part I) [Part I: 'Day1 to Day21 for Dose 1, 2,3 &4 and Day1 to Day45 for Dose group 5,6 & 7]
Frequency of subjects with drug-related Adverse Events (AEs) (Part I)
Secondary Outcome Measures
- Cmax (Part I) [for dose 1 & 2: up to 168h, for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h]
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
- AUC0-infinity (Part I) [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-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
- AUC0-tz [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]
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
- t1/2 (Part I) [for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h]
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
- Tmax (Part I) [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 (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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 45 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
Inclusion criteria:
-
Healthy male subjects
-
Subjects must be able to understand and comply with study requirements
-
Age from 18 to 55 years
-
BMI range: from 18.5 to 29.9 kg/m2
-
Known genotype as specified in the study protocol
Exclusion criteria:
- Any relevant deviation from healthy conditions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1334.1.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01843972
Other Study ID Numbers:
- 1334.1
- 2012-005721-67
First Posted:
May 1, 2013
Last Update Posted:
Jun 27, 2016
Last Verified:
May 1, 2016
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo (Part I) | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Tablet (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | placebo solution Placebo: placebo solution | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | single dose given as 1 tablet BI 691751: 1 tablet (10 mg) | 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. |
| Period Title: Overall Study | ||||||||||
| STARTED | 13 | 6 | 5 | 6 | 6 | 6 | 5 | 5 | 17 | 12 |
| COMPLETED | 13 | 6 | 5 | 6 | 5 | 6 | 5 | 5 | 17 | 12 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo (Part I) | BI 691751dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Tablet (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | placebo solution Placebo: placebo solution | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | single dose given as 1 tablet BI 691751: 1 tablet (10 mg) | 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. | Total of all reporting groups |
| Overall Participants | 13 | 6 | 5 | 6 | 6 | 6 | 5 | 5 | 17 | 12 | 81 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||
| Mean (Standard Deviation) [years] |
28.3
(8.2)
|
31.2
(8.0)
|
32.0
(8.4)
|
34.5
(6.8)
|
26.5
(5.2)
|
37.5
(6.0)
|
29.2
(2.6)
|
30.2
(8.0)
|
32.2
(9.3)
|
35.8
(10.2)
|
31.8
(8.3)
|
| 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%
|
| Male |
13
100%
|
6
100%
|
5
100%
|
6
100%
|
6
100%
|
6
100%
|
5
100%
|
5
100%
|
17
100%
|
12
100%
|
81
100%
|
Outcome Measures
| Title | AUC0-72h (Part II) |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol set for evaluation of bioavailability (PPS-BA). Only subjects with calculable PK parameter were analysed. |
| Arm/Group Title | BI 691751 Tablet Extensive Metabolizers (Part II) | BI 691751 Tablet Poor Metabolizers (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|
| Arm/Group Description | single dose given as 1 tablet; extensive metabolizers; BI 691751: 1 tablet (10 mg) | single dose given as 1 tablet; poor metabolizers; BI 691751: 1 tablet (10 mg) | 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. |
| Measure Participants | 12 | 5 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
2740
(26.1)
|
3050
(20.5)
|
2800
(22.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Tablet Extensive Metabolizers (Part II), BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|
| Comments | Only extensive CYP2D6 metabolisers were selected: 12 (all) subjects of group 'BI 691751 tablet extensive metabolizers (part II)' and 7 (all investigated) subjects of group 'BI 691751 solution (part II) '. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio (net) |
| Estimated Value | 97.88 | |
| Confidence Interval |
(2-Sided) 90% 79.963 to 119.809 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 24.8 |
|
| Estimation Comments | The geometric mean ratio is calculated as the geometric mean of 'BI 691751 tablet extensive metabolizers (part II)' divided by the geometric mean of 'BI 691751 solution (part II)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Tablet Extensive Metabolizers (Part II), BI 691751 Tablet Poor Metabolizers (Part II) |
|---|---|---|
| Comments | 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)'). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio (net) |
| Estimated Value | 111.20 | |
| Confidence Interval |
(2-Sided) 90% 88.596 to 139.576 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 24.7 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of the poor metabolisers divided by the geometric mean of the extensive metabolisers. | |
| Title | Cmax (Part II) |
|---|---|
| Description | Cmax (maximum measured concentration of the analyte of BI 691751 in plasma) (part II) |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PPS-BA. Only subjects with calculable PK parameter were analysed. |
| Arm/Group Title | BI 691751 Tablet Extensive Metabolizers (Part II) | BI 691751 Tablet Poor Metabolizers (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|
| Arm/Group Description | single dose given as 1 tablet; extensive metabolizers; BI 691751: 1 tablet (10 mg) | single dose given as 1 tablet; poor metabolizers; BI 691751: 1 tablet (10 mg) | 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. |
| Measure Participants | 12 | 5 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
223
(33.6)
|
207
(31.3)
|
220
(14.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Tablet Extensive Metabolizers (Part II), BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|
| Comments | Only extensive CYP2D6 metabolisers were selected: 12 (all) subjects of group 'BI 691751 tablet extensive metabolizers (part II)' and 7 (all investigated) subjects of group 'BI 691751 solution (part II) '. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio (net) |
| Estimated Value | 101.31 | |
| Confidence Interval |
(2-Sided) 90% 80.593 to 127.351 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 28.2 |
|
| Estimation Comments | The geometric mean ratio is calculated as the geometric mean of 'BI 691751 tablet extensive metabolizers (part II)' divided by the geometric mean of 'BI 691751 solution (part II)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Tablet Extensive Metabolizers (Part II), BI 691751 Tablet Poor Metabolizers (Part II) |
|---|---|---|
| Comments | 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)'). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio (net) |
| Estimated Value | 92.69 | |
| Confidence Interval |
(2-Sided) 90% 68.662 to 125.119 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 33.0 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of the poor metabolisers divided by the geometric mean of the extensive metabolisers. | |
| Title | Cmax (Part I) |
|---|---|
| Description | 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 |
| Time Frame | for dose 1 & 2: up to 168h, for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | 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. |
| Measure Participants | 4 | 5 | 6 | 6 | 6 | 5 | 5 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
3.45
(15.5)
|
18.3
(39.3)
|
88.9
(59.1)
|
729
(21.5)
|
1320
(31.5)
|
3320
(46.7)
|
4180
(22.2)
|
220
(14.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Dose 4 (Part I), BI 691751 Dose 5 (Part I), BI 691751 Dose 6 (Part I), BI 691751 Dose 7 (Part I) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | This was non-confirmatory testing. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 1.0233 | |
| Confidence Interval |
(2-Sided) 95% 0.8265 to 1.2201 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | AUC0-infinity (Part I) |
|---|---|
| Description | 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 |
| Time Frame | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
Outcome Measure Data
| Analysis Population Description |
|---|
| PPS-DP. Only subjects with calculable PK parameter were analysed. |
| Arm/Group Title | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | 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. |
| Measure Participants | 0 | 0 | 6 | 5 | 6 | 5 | 5 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
1140
(34.5)
|
7250
(15.9)
|
11900
(27.2)
|
24500
(20.0)
|
41000
(26.9)
|
3630
(28.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Dose 4 (Part I), BI 691751 Dose 5 (Part I), BI 691751 Dose 6 (Part I), BI 691751 Dose 7 (Part I) |
|---|---|---|
| Comments | Dose proportionality of BI 691751 was explored using a power model (regression model applied to log-transformed data). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | This was non-confirmatory testing. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.9686 | |
| Confidence Interval |
(2-Sided) 95% 0.8107 to 1.1266 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | AUC0-tz |
|---|---|
| Description | 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 |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PPS-DP for part I and PPS-BA for part II. Only subjects with calculable PK parameter were analysed. |
| Arm/Group Title | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Tablet Extensive Metabolizers (Part II) | BI 691751 Tablet Poor Metabolizers (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | single dose given as 1 tablet; extensive metabolizers; BI 691751: 1 tablet (10 mg) | single dose given as 1 tablet; poor metabolizers; BI 691751: 1 tablet (10 mg) | 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. |
| Measure Participants | 0 | 5 | 6 | 6 | 6 | 5 | 5 | 12 | 5 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
29.5
(18.4)
|
791
(45.4)
|
6310
(15.4)
|
11400
(28.3)
|
24100
(21.1)
|
40500
(27.2)
|
3150
(32.0)
|
3460
(17.4)
|
3300
(28.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Solution (Part II); Extensive Metabolizers, BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|
| Comments | Only extensive CYP2D6 metabolisers were selected: 12 (all) subjects of group 'BI 691751 tablet extensive metabolizers (part II)' and 7 (all investigated) subjects of group 'BI 691751 solution (part II) '. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio (net) |
| Estimated Value | 95.48 | |
| Confidence Interval |
(2-Sided) 90% 74.414 to 122.511 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 30.8 |
|
| Estimation Comments | The geometric mean ratio is calculated as the geometric mean of 'BI 691751 tablet extensive metabolizers (part II)' divided by the geometric mean of 'BI 691751 solution (part II)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Solution (Part II); Extensive Metabolizers, BI 691751 Tablet Poor Metabolizers (Part II) |
|---|---|---|
| Comments | 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)'). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio (net) |
| Estimated Value | 109.80 | |
| Confidence Interval |
(2-Sided) 90% 84.376 to 142.894 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 28.8 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of the poor metabolisers divided by the geometric mean of the extensive metabolisers. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | BI 691751 Dose 4 (Part I), BI 691751 Dose 5 (Part I), BI 691751 Dose 6 (Part I), BI 691751 Dose 7 (Part I) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | This was non-confirmatory testing. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 1.0312 | |
| Confidence Interval |
(2-Sided) 95% 0.833 to 1.1790 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | t1/2 (Part I) |
|---|---|
| Description | 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 |
| Time Frame | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | 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. |
| Measure Participants | 0 | 0 | 6 | 5 | 6 | 5 | 5 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [h] |
65.4
(37.8)
|
97.4
(63.3)
|
74.9
(49.2)
|
57.2
(34.3)
|
78.3
(16.9)
|
59.4
(57.1)
|
| Title | Tmax (Part I) |
|---|---|
| Description | 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 |
| Time Frame | for dose 1 & 2: up to 168 hours (h), for dose 3 & 4: up to 240h, for dose 5 to 8: up to 720h |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Solution (Part II); Extensive Metabolizers |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | 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. |
| Measure Participants | 4 | 5 | 6 | 6 | 6 | 5 | 5 | 7 |
| Median (Full Range) [h] |
0.667
|
0.667
|
0.842
|
0.500
|
0.350
|
0.667
|
0.667
|
0.667
|
| Title | Frequency of Subjects With Drug-related Adverse Events (Part I) |
|---|---|
| Description | Frequency of subjects with drug-related Adverse Events (AEs) (Part I) |
| Time Frame | Part I: 'Day1 to Day21 for Dose 1, 2,3 &4 and Day1 to Day45 for Dose group 5,6 & 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated Set (TS): all subjects who were documented to have taken at least 1 dose of study medication. |
| Arm/Group Title | Placebo (Part I) | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | placebo solution Placebo: placebo solution | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) |
| Measure Participants | 13 | 6 | 5 | 6 | 6 | 6 | 5 | 5 |
| Number [Participants] |
1
7.7%
|
0
0%
|
1
20%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
Adverse Events
| Time Frame | 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. | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||||||||||||||||
| Arm/Group Title | Placebo (Part I) | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Tablet (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers | ||||||||||
| Arm/Group Description | placebo solution Placebo: placebo solution | single dose given as oral solution BI 691751: oral solution BI 69175, dose 1 (0.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 2 (1.5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 3 (5 mg powder) | single dose given as oral solution BI 691751: oral solution BI 69175, dose 4 (15 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 5 (30 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 6 (60 mg powder) | single dose given as oral solution BI 691751: oral solution BI 691751, dose 7 (90 mg powder) | single dose given as 1 tablet BI 691751: 1 tablet (10 mg) | 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. | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| Placebo (Part I) | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Tablet (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers | |||||||||||
| 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| Placebo (Part I) | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Tablet (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers | |||||||||||
| 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 | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 1/12 (8.3%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Contusion | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 1/12 (8.3%) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| Placebo (Part I) | BI 691751 Dose 1 (Part I) | BI 691751 Dose 2 (Part I) | BI 691751 Dose 3 (Part I) | BI 691751 Dose 4 (Part I) | BI 691751 Dose 5 (Part I) | BI 691751 Dose 6 (Part I) | BI 691751 Dose 7 (Part I) | BI 691751 Tablet (Part II) | BI 691751 Solution (Part II); Extensive Metabolizers | |||||||||||
| 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 | 5/13 (38.5%) | 1/6 (16.7%) | 2/5 (40%) | 2/6 (33.3%) | 2/6 (33.3%) | 1/6 (16.7%) | 3/5 (60%) | 4/5 (80%) | 5/17 (29.4%) | 3/12 (25%) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Tachycardia | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Eye disorders | ||||||||||||||||||||
| Eye irritation | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal pain upper | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/17 (0%) | 1/12 (8.3%) | ||||||||||
| Aphthous stomatitis | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 1/12 (8.3%) | ||||||||||
| Diarrhoea | 1/13 (7.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Flatulence | 1/13 (7.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Nausea | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Toothache | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Vomiting | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Influenza | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 1/12 (8.3%) | ||||||||||
| Nasopharyngitis | 2/13 (15.4%) | 1/6 (16.7%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 2/5 (40%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Arthropod sting | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Laceration | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Muscle strain | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Road traffic accident | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 1/12 (8.3%) | ||||||||||
| Thermal burn | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Arthralgia | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 1/12 (8.3%) | ||||||||||
| Muscle spasms | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Musculoskeletal pain | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Musculoskeletal stiffness | 1/13 (7.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Myalgia | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Neck pain | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Headache | 0/13 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 2/5 (40%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Syncope | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Cough | 0/13 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Epistaxis | 1/13 (7.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Blister | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Haematoma | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/17 (5.9%) | 0/12 (0%) | ||||||||||
| Hot flush | 0/13 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/17 (0%) | 0/12 (0%) | ||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
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:
NCT01843972
Other Study ID Numbers:
- 1334.1
- 2012-005721-67
First Posted:
May 1, 2013
Last Update Posted:
Jun 27, 2016
Last Verified:
May 1, 2016