Trial Outcomes & Findings for A Study to Test How Healthy Men Tolerate Different Doses of BI 1595043 (NCT NCT04789304)
NCT ID: NCT04789304
Last Updated: 2024-02-21
Results Overview
Percentage of participants with drug-related adverse events (AEs). The causal relationship of AEs to the investigational product was judged by the investigator. The investigator was asked to record a 'yes' if there was, in his/her judgement, a reasonable causal relationship between the investigational product administered and the AE or a 'no' if there was, in his/her judgement, no reasonable causal relationship between the investigational product administered and the AE.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
From first drug administration until end of trial examination, up to 30 days.
Results posted on
2024-02-21
Participant Flow
A double-blind, randomised, placebo-controlled, parallel group trial to investigate the safety and tolerability of BI 1595043 in healthy male subjects after oral administration of multiple rising doses of 14 days.
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they strictly met all inclusion and none of the exclusion criteria. All subjects were informed that they were free to withdraw their consent at any time during the trial without penalty or prejudice. Subjects were recruited to a dose group according to their temporal availability and randomised within each dose group in a 4:1 ratio (trial drug to placebo).
Participant milestones
| Measure |
Placebo / Placebo + Midazolam
Film-coated tablets of Placebo, matching to 5 milligram (mg) and 25 mg BI 1595043,were administered orally once daily with 240 milliliter (mL) of water to the corresponding dose group.
Patients included in the placebo arm corresponding to dose group 3, also received a single oral dose of 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam on Day - 1, Day 1 and Day 18.
|
15 mg BI 1595043 qd
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
6
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Test How Healthy Men Tolerate Different Doses of BI 1595043
Baseline characteristics by cohort
| Measure |
Placebo / Placebo + Midazolam
n=6 Participants
Film-coated tablets of Placebo, matching to 5 milligram (mg) and 25 mg BI 1595043,were administered orally once daily with 240 milliliter (mL) of water to the corresponding dose group.
Patients included in the placebo arm corresponding to dose group 3, also received a single oral dose of 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam on Day - 1, Day 1 and Day 18.
|
15 mg BI 1595043 qd
n=8 Participants
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 Participants
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
n=8 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
39.8 Years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
30.5 Years
STANDARD_DEVIATION 7.8 • n=7 Participants
|
30.6 Years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
40.8 Years
STANDARD_DEVIATION 5.8 • n=4 Participants
|
35.1 Years
STANDARD_DEVIATION 9.3 • n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
30 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
29 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: From first drug administration until end of trial examination, up to 30 days.Population: Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
Percentage of participants with drug-related adverse events (AEs). The causal relationship of AEs to the investigational product was judged by the investigator. The investigator was asked to record a 'yes' if there was, in his/her judgement, a reasonable causal relationship between the investigational product administered and the AE or a 'no' if there was, in his/her judgement, no reasonable causal relationship between the investigational product administered and the AE.
Outcome measures
| Measure |
60 mg BI 1595043 qd + Midazolam
n=8 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
15 mg BI 1595043 qd
n=6 Participants
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 Participants
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
n=8 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Percentage of Participants With Drug-related Adverse Events (AEs)
|
25.0 Percentage of participants
|
0 Percentage of participants
|
12.5 Percentage of participants
|
37.5 Percentage of participants
|
SECONDARY outcome
Timeframe: 0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value for one period to the statistical assessment. Only participants with non-missing values were included.
Area under the concentration-time curve of BI 1595043 in plasma at steady state over a uniform dosing interval τ (AUC0-τ,ss) after the last dose of BI 1595043.
Outcome measures
| Measure |
60 mg BI 1595043 qd + Midazolam
n=7 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
15 mg BI 1595043 qd
n=8 Participants
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 Participants
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUC0-τ,ss)
|
8170 Hours*nanomol per Liter
Geometric Coefficient of Variation 18.5
|
1970 Hours*nanomol per Liter
Geometric Coefficient of Variation 22.1
|
3630 Hours*nanomol per Liter
Geometric Coefficient of Variation 10.2
|
—
|
SECONDARY outcome
Timeframe: 0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value for one period to the statistical assessment. Only participants with non-missing values were included.
Maximum measured concentration of BI 1595043 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after the last dose of BI 1595043.
Outcome measures
| Measure |
60 mg BI 1595043 qd + Midazolam
n=7 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
15 mg BI 1595043 qd
n=8 Participants
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 Participants
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Maximum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
|
1630 Nanomol per Liter
Geometric Coefficient of Variation 36.8
|
333 Nanomol per Liter
Geometric Coefficient of Variation 22.1
|
797 Nanomol per Liter
Geometric Coefficient of Variation 23.3
|
—
|
SECONDARY outcome
Timeframe: 0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value for one period to the statistical assessment. Only participants with non-missing values were included.
Minimum measured concentration of BI 1595043 in plasma at steady state over a uniform dosing interval τ (Cmin,ss) after the last dose of BI 1595043.
Outcome measures
| Measure |
60 mg BI 1595043 qd + Midazolam
n=7 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
15 mg BI 1595043 qd
n=8 Participants
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 Participants
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Minimum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss)
|
36.4 Nanomole per Liter
Geometric Coefficient of Variation 33.4
|
12.7 Nanomole per Liter
Geometric Coefficient of Variation 58.6
|
17.7 Nanomole per Liter
Geometric Coefficient of Variation 13.6
|
—
|
SECONDARY outcome
Timeframe: 0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value for one period to the statistical assessment. Only participants with non-missing values were included.
Accumulation ratio based on maximum measured concentration of BI 1595043 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) (RA, Cmax), after the last dose. RA,Cmax = Cmax after last dose / Cmax after first dose.
Outcome measures
| Measure |
60 mg BI 1595043 qd + Midazolam
n=7 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
15 mg BI 1595043 qd
n=8 Participants
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 Participants
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Accumulation Ratio Based on Maximum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) (RA, Cmax)
|
1.09 Ratio
Geometric Coefficient of Variation 31.4
|
0.894 Ratio
Geometric Coefficient of Variation 19.9
|
1.12 Ratio
Geometric Coefficient of Variation 30.3
|
—
|
SECONDARY outcome
Timeframe: 0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value for one period to the statistical assessment.
Accumulation ratio based on area under the concentration-time curve of BI 1595043 in plasma at steady state over a uniform dosing interval τ (AUC0-τ,ss) (RA, AUC). RA,AUC = AUC0-\\tau after last dose / AUC0-\\tau after first dose.
Outcome measures
| Measure |
60 mg BI 1595043 qd + Midazolam
n=8 Participants
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
15 mg BI 1595043 qd
n=8 Participants
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 Participants
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Accumulation Ratio Based on Area Under the Concentration-time Curve of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUC0-τ,ss) (RA, AUC)
|
1.11 Ratio
Geometric Coefficient of Variation 4.97
|
1.04 Ratio
Geometric Coefficient of Variation 4.93
|
1.06 Ratio
Geometric Coefficient of Variation 11.4
|
—
|
Adverse Events
Placebo / Placebo + Midazolam
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
15 mg BI 1595043 qd
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
30 mg BI 1595043 qd
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
60 mg BI 1595043 qd + Midazolam
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo / Placebo + Midazolam
n=6 participants at risk
Film-coated tablets of Placebo, matching to 5 milligram (mg) and 25 mg BI 1595043,were administered orally once daily with 240 milliliter (mL) of water to the corresponding dose group.
Patients included in the placebo arm corresponding to dose group 3, also received a single oral dose of 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam on Day - 1, Day 1 and Day 18.
|
15 mg BI 1595043 qd
n=8 participants at risk
3 film-coated tablets of 5 milligram (mg) (total dose: 15 mg) BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 1.
|
30 mg BI 1595043 qd
n=8 participants at risk
1 film-coated tablet of 5 mg and 1 film-coated tablet of 25 mg (total dose: 30 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. Dose group 2.
|
60 mg BI 1595043 qd + Midazolam
n=8 participants at risk
2 film-coated tablets of 5 mg and 2 film-coated tablets of 25 mg (total dose: 60 mg) of BI 1595043 were administered orally once daily (qd), with 240 mL of water after an overnight fast of at least 10 hours (h) on Day 1, followed by a washout of 4 days and from Day 5 to Day 18. On Day - 1, Day 1 and Day 18, 75 µg (5 mg/5 mL diluted to 50 µg/mL·1.5 mL) solution for injection of midazolam was administered as single oral dose. Dose group 3.
|
|---|---|---|---|---|
|
Eye disorders
Eye irritation
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
25.0%
2/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Eye disorders
Blepharitis
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Eye disorders
Lenticular opacities
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Eye disorders
Visual impairment
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Nervous system disorders
Headache
|
50.0%
3/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
37.5%
3/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
25.0%
2/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
25.0%
2/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
16.7%
1/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Gastrointestinal disorders
Aphthous ulcer
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Infections and infestations
Conjunctivitis
|
16.7%
1/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Injury, poisoning and procedural complications
Muscle injury
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Investigations
Liver function test increased
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
|
Vascular disorders
Haematoma
|
0.00%
0/6 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
12.5%
1/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
0.00%
0/8 • From first drug administration until end of trial examination, up to 30 days.
Treated Set (TS): The TS included all subjects who were randomised and treated with at least one dose of trial drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER