To Investigate the Safety, Tolerability, Pharmacokinetics and the Relative Bioavailability of BI 1026706
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT01763333
Collaborator
(none)
80
1
2
7.9
10.2
Study Details
Study Description
Brief Summary
To investigate the safety, tolerability, pharmacokinetics and the relative bioavailability of BI 1026706
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
80 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
Single
Primary Purpose:
Treatment
Official Title:
Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 1026706 in Healthy Male Volunteers in a Partially Randomised, Single-blind, Placebo-controlled Trial, and Investigation of Relative Bioavailability of BI 1026706 (Open-label, Randomised, Four-way Cross-over)
Actual Study Start Date
:
Jan 8, 2013
Actual Primary Completion Date
:
Sep 4, 2013
Actual Study Completion Date
:
Sep 4, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 BI 1026706 single rising dose part single rising doses of BI 1026706 |
Drug: BI 1026706 Placebo
Placebo to BI 1026706
Drug: BI 1026706
different dose formulations
|
| Experimental: 2 BI 1026706 bioavailability part bioavailability part of BI 1026706 |
Drug: BI 1026706
different dose formulations
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects With Drug Related Adverse Events [From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part.]
Percentage of subjects with drug related adverse events.
Secondary Outcome Measures
- Cmax [-2.0 hours (h) before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing]
Maximum measured concentration of the analyte in plasma (Cmax). The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) included all subjects of the TS-BA who provided observations under the reference treatment (R1) or test treatment (T1) for at least one of the endpoints Cmax, AUC0-tz, or AUC0-inf,without experiencing emesis at or before two times median tmax and without important protocol violations (PVs) relevant to the statistical evaluation of pharmacokinetic (PK). The same definition applies for the analysis set PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1.
- Tmax (Time From Dosing to Maximum Measured Concentration) [-2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing]
Time from dosing to maximum measured concentration (tmax).
- AUC0-inf [-2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing]
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).
- AUC0- tz [-2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing]
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0- tz).
- t1/2 (Terminal Half-life of the Analyte in Plasma) [-2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing]
Terminal half-life of the analyte in plasma (t1/2).
- f t1-t2 (SRD-Part) [0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours]
Fraction of analyte eliminated in urine from the time point t1 (0h) to time point t2 (72h) (f t1-t2).
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
Exclusion criteria:
- Any relevant deviation from healthy conditions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1320.1.1 Boehringer Ingelheim Investigational Site | Ingelheim | 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:
NCT01763333
Other Study ID Numbers:
- 1320.1
- 2012-002366-12
First Posted:
Jan 8, 2013
Last Update Posted:
Mar 25, 2019
Last Verified:
Dec 1, 2018
Study Results
Participant Flow
| Recruitment Details | Subjects were recruited from the volunteers' pool of the Human Pharmacology Centre of Boehringer Ingelheim (BI) Pharma GmbH & Co. KG, Ingelheim, Germany.Only male subjects were included because no data on reproductive toxicology was available. |
|---|---|
| Pre-assignment Detail | 68 subjects were randomised for single rising dose (SRD) part &12 subjects for bioavailability(BA) part of study. |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | R1/T1/R2/T2 (BA - Part) | T1/T2/R1/R2 (BA - Part) | R2/R1/T2/T1 (BA - Part) | T2/R2/T1/R1 (BA - Part) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100mg film coated tablet (R1) under fasted condition, followed by 100mg film coated tablet (T1) under fed condition, 100 mg drinking solution (R2) under fasting and in the last treatment period with 100 mg drinking solution (T2) under fed condition. There was washout period of 7days between the respective treatments. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning. First they were treated with 100mg film coated tablet (T1) under fed condition, followed by 100 mg drinking solution (T2) under fed condition, 100mg film coated tablet (R1) under fasted condition and in the last treatment period with 100 mg drinking solution (R2) under fasting condition. There was a washout period of 7days between the respective treatments. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (R2) under fasting condition, followed by 100mg film coated tablet (R1) under fasted condition,100 mg drinking solution (T2) under fed condition and in the last treatment period with 100mg film coated tablet (T1) under fed condition. There was washout period of 7days between the respective treatments. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (T2) under fed condition, followed by 100 mg drinking solution (R2) under fasting, 100mg film coated tablet (T1) under fed condition and in the last treatment period with 100mg film coated tablet (R1) under fasted condition. There was washout period of 7days between the respective treatments. |
| Period Title: Overall Study | ||||||||||||||
| STARTED | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 18 | 3 | 3 | 3 | 3 |
| COMPLETED | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 18 | 3 | 3 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | R1/T1/R2/T2 (BA - Part) | T1/T2/R1/R2 (BA - Part) | R2/R1/T2/T1 (BA - Part) | T2/R2/T1/R1 (BA - Part) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100mg film coated tablet (R1) under fasted condition, followed by 100mg film coated tablet (T1) under fed condition, 100 mg drinking solution (R2) under fasting and in the last treatment period with 100 mg drinking solution (T2) under fed condition. There was washout period of 7days between the respective treatments. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning. First they were treated with 100mg film coated tablet (T1) under fed condition, followed by 100 mg drinking solution (T2) under fed condition, 100mg film coated tablet (R1) under fasted condition and in the last treatment period with 100 mg drinking solution (R2) under fasting condition. There was a washout period of 7days between the respective treatments. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (R2) under fasting condition, followed by 100mg film coated tablet (R1) under fasted condition,100 mg drinking solution (T2) under fed condition and in the last treatment period with 100mg film coated tablet (T1) under fed condition. There was washout period of 7days between the respective treatments. | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (T2) under fed condition, followed by 100 mg drinking solution (R2) under fasting, 100mg film coated tablet (T1) under fed condition and in the last treatment period with 100mg film coated tablet (R1) under fasted condition. There was washout period of 7days between the respective treatments. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 18 | 3 | 3 | 3 | 3 | 80 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||||||||
| Mean (Standard Deviation) [Years] |
38.8
(4.2)
|
39.0
(5.8)
|
35.5
(7.1)
|
39.5
(7.3)
|
42.0
(5.7)
|
39.7
(8.0)
|
43.4
(7.8)
|
35.7
(9.2)
|
32.4
(12.0)
|
35.9
(7.2)
|
32.7
(12.4)
|
27.0
(3.6)
|
26.7
(4.9)
|
27.0
(5.6)
|
36.3
(8.2)
|
| 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 |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
4
100%
|
6
100%
|
5
100%
|
6
100%
|
5
100%
|
18
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
80
100%
|
Outcome Measures
| Title | Number of Subjects With Drug Related Adverse Events |
|---|---|
| Description | Percentage of subjects with drug related adverse events. |
| Time Frame | From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The treated set (TS) included all subjects who were documented to have taken at least one dose of study medication. |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | Subjects were treated with 100mg film coated tablet (T1) under fed condition. |
| Measure Participants | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 18 | 11 | 12 | 12 | 10 |
| Number [Percentage of participants] |
0.0
0%
|
33.3
555%
|
16.7
278.3%
|
16.7
278.3%
|
25.0
625%
|
0.0
0%
|
20.0
400%
|
16.7
278.3%
|
60.0
1200%
|
22.2
123.3%
|
0.0
0%
|
8.3
276.7%
|
16.7
556.7%
|
20.0
666.7%
|
| Title | Cmax |
|---|---|
| Description | Maximum measured concentration of the analyte in plasma (Cmax). The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) included all subjects of the TS-BA who provided observations under the reference treatment (R1) or test treatment (T1) for at least one of the endpoints Cmax, AUC0-tz, or AUC0-inf,without experiencing emesis at or before two times median tmax and without important protocol violations (PVs) relevant to the statistical evaluation of pharmacokinetic (PK). The same definition applies for the analysis set PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1. |
| Time Frame | -2.0 hours (h) before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1 |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | Subjects were treated with 100mg film coated tablet (T1) under fed condition. |
| Measure Participants | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 11 | 12 | 12 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [nanomoles Per Litre (nmol/L)] |
117
(33.1)
|
268
(42.9)
|
623
(40.9)
|
728
(26.8)
|
1430
(80.0)
|
112
(32.9)
|
1150
(47.1)
|
2210
(28.0)
|
3090
(24.8)
|
1340
(32.0)
|
706
(33.5)
|
560
(34.8)
|
651
(34.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Tablet 25 mg (SRD - Part), BI 1026706 - Tablet 50 mg (SRD - Part), BI 1026706 - Tablet 100 mg (SRD - Part), BI 1026706 - Tablet 200 mg (SRD - Part), BI 1026706 - Tablet 400 mg (SRD - Part) |
|---|---|---|
| Comments | This was non confirmatory testing (Single dose). Dose proportionality of tablets for Cmax was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.8728 | |
| Confidence Interval |
(2-Sided) 95% 0.6942 to 1.0513 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. PK endpoints on the log-transformed scale. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Solution 10 mg (SRD - Part), BI 1026706 - Solution 100 mg (SRD - Part), BI 1026706 - Solution 200 mg (SRD - Part), BI 1026706 - Solution 400 mg (SRD - Part) |
|---|---|---|
| Comments | This was non confirmatory testing (Single dose). Dose proportionality of solution for Cmax was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.9341 | |
| Confidence Interval |
(2-Sided) 95% 0.8277 to 1.0405 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. PK endpoints on the log-transformed scale. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - 100 mg Solution Fed (T2), BI 1026706 - Tablet 100 mg Fasted (R1) |
|---|---|---|
| Comments | Relative bioavailability comparison Tab. fed (T1): Tab. fasted (R1) for Cmax. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 112.74 | |
| Confidence Interval |
(2-Sided) 90% 95.579 to 132.993 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo (SRD - Part), BI 1026706 - Solution 100 mg Fasted (R2) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for Cmax. The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 52.66 | |
| Confidence Interval |
(2-Sided) 90% 40.488 to 68.499 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo (SRD - Part), BI 1026706 - 100 mg Solution Fed (T2) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for Cmax. The per protocol set for the evaluation of relative bioavailability of R2 vs R1 (PPS-BA-R2-R1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 239.63 | |
| Confidence Interval |
(2-Sided) 90% 197.445 to 290.830 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Solution 100 mg Fasted (R2), BI 1026706 - Tablet 100 mg Fasted (R1) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for Cmax. The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 105.47 | |
| Confidence Interval |
(2-Sided) 90% 85.427 to 130.208 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
| Title | Tmax (Time From Dosing to Maximum Measured Concentration) |
|---|---|
| Description | Time from dosing to maximum measured concentration (tmax). |
| Time Frame | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | Subjects were treated with 100mg film coated tablet (T1) under fed condition. |
| Measure Participants | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 11 | 12 | 12 | 10 |
| Median (Full Range) [hours] |
1.74
|
1.51
|
1.75
|
1.25
|
2.23
|
0.63
|
0.50
|
0.75
|
0.75
|
0.52
|
0.75
|
1.74
|
1.26
|
| Title | AUC0-inf |
|---|---|
| Description | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). |
| Time Frame | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1 |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | Subjects were treated with 100mg film coated tablet (T1) under fed condition. |
| Measure Participants | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 11 | 12 | 12 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
768
(28.6)
|
1690
(51.8)
|
3990
(30.9)
|
4040
(29.4)
|
8900
(85.1)
|
428
(41.9)
|
3220
(43.5)
|
7790
(26.9)
|
11300
(28.3)
|
4590
(33.1)
|
3380
(28.6)
|
3270
(28.3)
|
2930
(40.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Tablet 25 mg (SRD - Part), BI 1026706 - Tablet 50 mg (SRD - Part), BI 1026706 - Tablet 100 mg (SRD - Part), BI 1026706 - Tablet 200 mg (SRD - Part), BI 1026706 - Tablet 400 mg (SRD - Part) |
|---|---|---|
| Comments | This was non confirmatory testing (Single dose).Dose proportionality of tablets for AUC0-inf was analysed.The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.8341 | |
| Confidence Interval |
(2-Sided) 95% 0.6485 to 1.0198 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. PK endpoints on the log-transformed scale. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Solution 10 mg (SRD - Part), BI 1026706 - Solution 100 mg (SRD - Part), BI 1026706 - Solution 200 mg (SRD - Part), BI 1026706 - Solution 400 mg (SRD - Part) |
|---|---|---|
| Comments | This was non confirmatory testing (Single dose).Dose proportionality of solution for AUC0-inf was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.9149 | |
| Confidence Interval |
(2-Sided) 95% 0.8059 to 1.0239 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. PK endpoints on the log-transformed scale. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - 100 mg Solution Fed (T2), BI 1026706 - Tablet 100 mg Fasted (R1) |
|---|---|---|
| Comments | Relative bioavailability comparison Tab. fed (T1): Tab. fasted (R1) for AUC0-inf. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean Ratio |
| Estimated Value | 86.61 | |
| Confidence Interval |
(2-Sided) 90% 76.529 to 98.029 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo (SRD - Part), BI 1026706 - Solution 100 mg Fasted (R2) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 74.44 | |
| Confidence Interval |
(2-Sided) 90% 66.322 to 83.562 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo (SRD - Part), BI 1026706 - 100 mg Solution Fed (T2) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of R2 vs R1 (PPS-BA-R2-R1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 137.25 | |
| Confidence Interval |
(2-Sided) 90% 119.708 to 157.353 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Solution 100 mg Fasted (R2), BI 1026706 - Tablet 100 mg Fasted (R1) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 116.48 | |
| Confidence Interval |
(2-Sided) 90% 111.462 to 121.724 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
| Title | AUC0- tz |
|---|---|
| Description | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0- tz). |
| Time Frame | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1 |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | Subjects were treated with 100mg film coated tablet (T1) under fed condition. |
| Measure Participants | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 11 | 12 | 12 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
741
(25.2)
|
1670
(51.8)
|
3950
(30.5)
|
3990
(28.6)
|
8830
(85.3)
|
403
(44.0)
|
3170
(27.0)
|
7710
(27.0)
|
11300
(28.3)
|
4550
(33.3)
|
3360
(28.9)
|
3240
(28.3)
|
2900
(40.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Tablet 25 mg (SRD - Part), BI 1026706 - Tablet 50 mg (SRD - Part), BI 1026706 - Tablet 100 mg (SRD - Part), BI 1026706 - Tablet 400 mg (SRD - Part) |
|---|---|---|
| Comments | This was non confirmatory testing (Single dose). Dose proportionality of tablets for AUC 0- tz was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.8428 | |
| Confidence Interval |
(2-Sided) 95% 0.6580 to 1.0275 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. PK endpoints on the log-transformed scale. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Solution 10 mg (SRD - Part), BI 1026706 - Solution 100 mg (SRD - Part), BI 1026706 - Solution 200 mg (SRD - Part), BI 1026706 - Solution 400 mg (SRD - Part) |
|---|---|---|
| Comments | This was non confirmatory testing (Single dose). Dose proportionality of solution for AUC0-tz was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Slope |
| Estimated Value | 0.9307 | |
| Confidence Interval |
(2-Sided) 95% 0.8187 to 1.0426 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - 100 mg Solution Fed (T2), BI 1026706 - Tablet 100 mg Fasted (R1) |
|---|---|---|
| Comments | Relative bioavailability comparison Tab. fed (T1) : Tab. fasted (R1) for AUC 0-tz. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean Ratio |
| Estimated Value | 86.16 | |
| Confidence Interval |
(2-Sided) 90% 75.735 to 98.027 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted geometric mean (gMean) ratio. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo (SRD - Part), BI 1026706 - Solution 100 mg Fasted (R2) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 74.42 | |
| Confidence Interval |
(2-Sided) 90% 65.979 to 83.941 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo (SRD - Part), BI 1026706 - 100 mg Solution Fed (T2) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of R2 vs R1(PPS-BA-R2-R1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 137.20 | |
| Confidence Interval |
(2-Sided) 90% 119.611 to 157.374 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | BI 1026706 - Solution 100 mg Fasted (R2), BI 1026706 - Tablet 100 mg Fasted (R1) |
|---|---|---|
| Comments | Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | gMean ratio |
| Estimated Value | 116.83 | |
| Confidence Interval |
(2-Sided) 90% 111.814 to 122.079 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Adjusted gMean ratio. | |
| Title | t1/2 (Terminal Half-life of the Analyte in Plasma) |
|---|---|
| Description | Terminal half-life of the analyte in plasma (t1/2). |
| Time Frame | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| TS-SRD and TS-BA |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | Subjects were treated with 100mg film coated tablet (T1) under fed condition. |
| Measure Participants | 6 | 6 | 6 | 6 | 4 | 6 | 5 | 6 | 5 | 11 | 12 | 12 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [hours] |
10.80
(75.7)
|
8.58
(54.3)
|
12.10
(26.6)
|
11.60
(43.2)
|
12.00
(22.7)
|
13.90
(82.1)
|
12.80
(54.7)
|
11.50
(50.3)
|
9.29
(27.3)
|
10.80
(36.0)
|
11.10
(53.9)
|
10.50
(46.9)
|
12.60
(28.4)
|
| Title | f t1-t2 (SRD-Part) |
|---|---|
| Description | Fraction of analyte eliminated in urine from the time point t1 (0h) to time point t2 (72h) (f t1-t2). |
| Time Frame | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| TS-SRD |
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. |
| Measure Participants | 6 | 4 | 6 | 6 | 4 | 6 | 5 | 6 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [Percentage] |
3.02
(21.1)
|
2.75
(51.2)
|
3.43
(33.4)
|
1.95
(27.2)
|
1.87
(45.3)
|
3.97
(40.8)
|
3.47
(23.9)
|
3.82
(32.8)
|
2.09
(7.44)
|
Adverse Events
| Time Frame | From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part. | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||
| Arm/Group Title | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) | ||||||||||||||
| Arm/Group Description | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | Subjects were treated with 100mg film coated tablet (T1) under fed condition. | ||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||
| BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) | |||||||||||||||
| 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||
| BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) | |||||||||||||||
| 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 | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||
| BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | BI 1026706 - Solution 100 mg Fasted (R2) | BI 1026706 - 100 mg Solution Fed (T2) | BI 1026706 - Tablet 100 mg Fasted (R1) | BI 1026706 - Tablet 100 mg Fed (T1) | |||||||||||||||
| 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 | 1/6 (16.7%) | 5/6 (83.3%) | 3/6 (50%) | 2/6 (33.3%) | 2/4 (50%) | 3/6 (50%) | 2/5 (40%) | 1/6 (16.7%) | 4/5 (80%) | 8/18 (44.4%) | 3/11 (27.3%) | 3/12 (25%) | 6/12 (50%) | 5/10 (50%) | ||||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||
| Ear discomfort | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | ||||||||||||||
| Ear pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 2/5 (40%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/10 (0%) | ||||||||||||||
| Diarrhoea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 2/5 (40%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Dry mouth | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Flatulence | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/10 (0%) | ||||||||||||||
| Haematochezia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/10 (0%) | ||||||||||||||
| Nausea | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/5 (20%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| General disorders | ||||||||||||||||||||||||||||
| Application site haematoma | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||
| Nasopharyngitis | 1/6 (16.7%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 1/5 (20%) | 4/18 (22.2%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Oral herpes | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Laceration | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Investigations | ||||||||||||||||||||||||||||
| Heart rate increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | ||||||||||||||
| Platelet count increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/10 (0%) | ||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Arthralgia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/4 (25%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Back pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Musculoskeletal pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/5 (20%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Tendon pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||
| Dizziness | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/10 (0%) | ||||||||||||||
| Headache | 0/6 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/4 (0%) | 0/6 (0%) | 2/5 (40%) | 1/6 (16.7%) | 0/5 (0%) | 3/18 (16.7%) | 1/11 (9.1%) | 1/12 (8.3%) | 3/12 (25%) | 2/10 (20%) | ||||||||||||||
| Presyncope | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/4 (25%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Dysuria | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Haematuria | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Dry throat | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Epistaxis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | ||||||||||||||
| Oropharyngeal pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 2/12 (16.7%) | 0/10 (0%) | ||||||||||||||
| Rhinorrhoea | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Alopecia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Pruritus | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | ||||||||||||||
| Skin irritation | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/18 (0%) | 0/11 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (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:
NCT01763333
Other Study ID Numbers:
- 1320.1
- 2012-002366-12
First Posted:
Jan 8, 2013
Last Update Posted:
Mar 25, 2019
Last Verified:
Dec 1, 2018