Trial Outcomes & Findings for A Study in Healthy Men to Test How BI 1358894 is Taken up and Handled by the Body (NCT NCT04567316)

Last Updated: 2025-02-27

Results Overview

Mass balance and recoveries of \[14C\] BI 1358894 total radioactivity in urine and faeces after single oral dose as percentage of the administered dose over the time interval from 0 to tz, where tz is the latest quantifiable data point across all participants. Urine collection intervals were within 2 hours (h) predose, 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336 h after dosing on Day 1 and to be continued in 24 h intervals, on days 21-22, 28-29, 35-36, 42-43, and 49-50, if necessary. Faeces collection intervals were started from approximately -48 h before drug administration and 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336 h after dosing on Day 1 and to be continued in 24 h intervals, on days 21-22, 28-29, 35-36, 42-43, and 49-50, if necessary.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

From within 2 hours predose up to 50 days after dosing. For detailed time frames please refer to the intervals given under "measure description" above.

Results posted on

2025-02-27

Participant Flow

This is a phase I, open-label trial to investigate metabolism and pharmacokinetics of a single dose of \[14C\] BI 1358894 administered as oral solution (Part1) and multiple doses of BI 1358894 administered as film-coated tablets (Part 2) in healthy male volunteers.

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).	100 mg BI 1358894 (Part 2) Multiple doses (MD) of 2 non-radiolabeled film-coated tablets of 50 milligram (mg) BI 1358894 were administered orally once daily (QD) from Day 1 to Day 21 with 240 milliliter (mL) of water .
Overall Study STARTED	8	7
Overall Study COMPLETED	8	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study in Healthy Men to Test How BI 1358894 is Taken up and Handled by the Body

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=8 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).	100 mg BI 1358894 (Part 2) n=7 Participants Multiple doses (MD) of 2 non-radiolabeled film-coated tablets of 50 milligram (mg) BI 1358894 were administered orally once daily (QD) from Day 1 to Day 21 with 240 milliliter (mL) of water .	Total n=15 Participants Total of all reporting groups
Age, Continuous	41.4 Years STANDARD_DEVIATION 19.2 • n=99 Participants	39.1 Years STANDARD_DEVIATION 20.0 • n=107 Participants	40.3 Years STANDARD_DEVIATION 18.9 • n=206 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	7 Participants n=107 Participants	15 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=99 Participants	7 Participants n=107 Participants	14 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	6 Participants n=99 Participants	5 Participants n=107 Participants	11 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: From within 2 hours predose up to 50 days after dosing. For detailed time frames please refer to the intervals given under "measure description" above.

Population: Pharmacokinetic set (PKS) Part 1: This subject set included all subjects in treated set (TS) who provided at least one primary or secondary PK parameter that was not excluded according to description above. Thus, a subject was included in PKS, even if he/she contributed only one pharmacokinetics (PK) parameter value to the statistical assessment. Only subjects with available data were included in the analysis.

Outcome measures

Outcome measures
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=7 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).
Part 1: Mass Balance and Recoveries of [14C] BI 1358894 Total Radioactivity in Urine and Faeces After Single Oral Dose (Fe0-tz)	85.8 Percentage of administered dose Geometric Coefficient of Variation 3.42

SECONDARY outcome

Timeframe: At 2 hours (h) before first drug administration and at 20 minutes (min), 40min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h, 240h, 288h, 336h, 485h, 653h after first drug administration.

Population: Pharmacokinetic set (PKS) Part 1: This subject set included all subjects in the TS who provided at least one primary or secondary PK parameter that was not excluded according to the description above. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value to the statistical assessment.

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) were determined for total \[14C\] BI 1358894 and non-radiolabeled BI 1358894 after single dose administration.

Outcome measures

Outcome measures
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=8 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).
Part 1: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) BI 1358894	13000 Hours * nanomol / Liter Geometric Coefficient of Variation 30.9
Part 1: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) [14C] BI 1358894-EQ	73200 Hours * nanomol / Liter Geometric Coefficient of Variation 26.8

SECONDARY outcome

Population: Pharmacokinetic set (PKS): This subject set included all subjects in the TS who provided at least one primary or secondary PK parameter that was not excluded according to the description above. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value to the statistical assessment.

Maximum measured concentration of the analyte in plasma (Cmax) determined for total \[14C\] BI 1358894 and non-radiolabeled BI 1358894 after single dose administration.

Outcome measures

Outcome measures
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=8 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).
Part 1: Maximum Measured Concentration of the Analyte in Plasma (Cmax) [14C] BI 1358894-EQ	2070 nanomol / Liter Geometric Coefficient of Variation 28.4
Part 1: Maximum Measured Concentration of the Analyte in Plasma (Cmax) BI 1358894	657 nanomol / Liter Geometric Coefficient of Variation 43.2

SECONDARY outcome

Timeframe: At 2 hours (h) before first drug administration and at 30 minutes (min), 1h, 2h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 14h and 24h after first drug administration.

Population: Pharmacokinetic set (PKS) Part 2: This subject set included all subjects in the TS who provided at least one primary or secondary PK parameter that was not excluded according to the description above. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value to the statistical assessment.

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours(AUC0-24) was determined for non-radiolabeled BI 1358894.

Outcome measures

Outcome measures
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=7 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).
Part 2: Area Under the Concentration-time Curve of Non-radiolabeled BI 1358894 in Plasma Over the Time Interval From 0 to 24 (AUC0-24)	5200 Hours*nanomol / Liter Geometric Coefficient of Variation 20.1

SECONDARY outcome

Timeframe: At 2 hours (h) before first drug administration and at 30 minutes (min), 1h, 2h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 14h and 24h after first drug administration.

Maximum measured concentration of the analyte in plasma (Cmax) was determined for non-radiolabeled BI 1358894.

Outcome measures

Outcome measures
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=7 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).
Part 2: Maximum Measured Concentration of Non-radiolabeled BI 1358894 in Plasma (Cmax)	551 nanomol / Liter Geometric Coefficient of Variation 39.1

SECONDARY outcome

Timeframe: At 480h, 480.5h, 481h, 482h, 484h, 485h, 486h, 487h,488h, 490h, 492h, 494h and 504h after first drug administration.

Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) was determined for non-radiolabeled BI 1358894. Tau = 24 hours.

Outcome measures

Outcome measures
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=7 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).
Part 2: Area Under the Concentration-time Curve of Non-radiolabeled BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)	14400 Hours * nanomol / Liter Geometric Coefficient of Variation 11.1

SECONDARY outcome

Timeframe: At 480h, 480.5h, 481h, 482h, 484h, 485h, 486h, 487h,488h, 490h, 492h, 494h and 504h after first drug administration.

Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmax,ss) was determined for non-radiolabeled BI 1358894. Tau = 24 hours.

Outcome measures

Outcome measures
Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=7 Participants Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).
Part 2: Maximum Measured Concentration of Non-radiolabeled BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)	1030 nanomol / Liter Geometric Coefficient of Variation 16.5

Adverse Events

100 mg [14C]-Radiolabeled BI 1358894 (Part 1)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

100 mg BI 1358894 (Part 2)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

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

Measure	100 mg [14C]-Radiolabeled BI 1358894 (Part 1) n=8 participants at risk Single dose (SD) of 100 milligram (mg) of radiolabeled BI 1358894 was administered as oral solution on Day 1. Oral solution contained a mixture of Carbon 14-radiolabelled BI 1358894 (\[14C\] BI 1358894) corresponding to a radioactive dose of 3.7 megabecquerels (MBq) (100 microcuries (μCi)) in a solution of 10 milliliter (mL) volume (concentration of BI 1358894 10 mg/mL).	100 mg BI 1358894 (Part 2) n=7 participants at risk Multiple doses (MD) of 2 non-radiolabeled film-coated tablets of 50 milligram (mg) BI 1358894 were administered orally once daily (QD) from Day 1 to Day 21 with 240 milliliter (mL) of water .
General disorders Catheter site irritation	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	42.9% 3/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Vessel puncture site haematoma	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	28.6% 2/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Catheter site haematoma	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Fatigue	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Malaise	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Medical device site irritation	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Catheter site erythema	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Thirst	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
General disorders Vessel puncture site pain	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Gingival pain	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Lip swelling	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Toothache	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Lip dry	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Gastrointestinal disorders Proctalgia	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Nervous system disorders Headache	37.5% 3/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Nervous system disorders Dizziness	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Nervous system disorders Head discomfort	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Nervous system disorders Somnolence	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Vascular disorders Haematoma	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	42.9% 3/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	28.6% 2/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Injury, poisoning and procedural complications Limb injury	12.5% 1/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	0.00% 0/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Psychiatric disorders Sleep disorder	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/8 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.	14.3% 1/7 • For all AEs, including all-cause mortality: From first drug administration until end of trial, up to 50 days for part 1 and up to 62 days for part 2. Treated Set (TS): This subject set included all subjects who entered the study who were documented to have received at least one dose of study drug.