Trial Outcomes & Findings for This Study Tests BI 1467335 in Healthy Male Volunteers. The Study Tests How Different Doses of BI 1467335 Are Taken up and Handled by the Body (NCT NCT03382509)

Last Updated: 2021-06-22

Results Overview

fe(urine, 0-t2), fraction of \[14C\]-radioactivity excreted in urine as percentage of the administered oral dose over the time interval from 0 to the last quantifiable time point.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

2 hours (h) prior to drug intake at Day 1 (SD group) and at the following intervals on Day 1 (SD group) and Day 28 (MD group): 0 to 4, 4 to 8, 8 to 12, 12 to 24 hours and every 24 hours thereafter from day 1 to day 14 following drug intake.

Results posted on

2021-06-22

Participant Flow

This was an open-label, phase I, single-arm, and 2 study parts trial with either single or multiple dose in healthy male participants. The single dose (SD) and multiple dose (MD) parts of the trial were conducted in different participants. The trial started with the MD part, while the SD part was scheduled close to Day 28 of the MD part.

All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensured that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any one of the specific entry criteria were not met.

Participant milestones

Participant milestones
Measure	BI 1467335 10 Milligram (mg) (SD) Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

This Study Tests BI 1467335 in Healthy Male Volunteers. The Study Tests How Different Doses of BI 1467335 Are Taken up and Handled by the Body

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) n=8 Participants Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.	Total n=16 Participants Total of all reporting groups
Age, Continuous	60.4 Years STANDARD_DEVIATION 4.5 • n=99 Participants	57.3 Years STANDARD_DEVIATION 10.9 • n=107 Participants	58.8 Years STANDARD_DEVIATION 8.2 • 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	8 Participants n=107 Participants	16 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 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	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	8 Participants n=99 Participants	8 Participants n=107 Participants	16 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: 2 hours (h) prior to drug intake at Day 1 (SD group) and at the following intervals on Day 1 (SD group) and Day 28 (MD group): 0 to 4, 4 to 8, 8 to 12, 12 to 24 hours and every 24 hours thereafter from day 1 to day 14 following drug intake.

Population: Pharmacokinetic parameter analysis set (PKS): This subject set included all subjects of the TS who provided at least 1 primary or secondary PK parameter that was not excluded because of protocol deviations relevant to the statistical evaluation of PK endpoints.

fe(urine, 0-t2), fraction of \[14C\]-radioactivity excreted in urine as percentage of the administered oral dose over the time interval from 0 to the last quantifiable time point.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) n=8 Participants Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Fraction of [14C]-Radioactivity Excreted in Urine as Percentage of the Administered Oral Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe(Urine,0-t2))	79.0 Percentage of dose excreted Geometric Coefficient of Variation 2.68	83.7 Percentage of dose excreted Geometric Coefficient of Variation 2.12

PRIMARY outcome

Timeframe: 2 hours (h) prior to drug intake at Day 1 (SD group) and at the following intervals on Day 1 (SD group) and Day 28 (MD group): every 24 hours from day 1 to day 14 following drug intake.

Population: PKS

fe(faeces,0-t2), fraction of \[14C\]-radioactivity excreted in faeces as percentage of the administered oral dose over the time interval from 0 to the last quantifiable time point. Time frame: 648 to 672 h, 672 to 696, 696 to 720, 720 to 744, 744to 768, 768 to 792, 792 to 816, 816 to 840, 840 to 864, 864 to 888, 888 to 912, 912 to 936, 936 to 960, 960 to 984, and 984 to 1008 after the dispense of study medication at Day 1 for the MD group.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) n=8 Participants Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Fraction of [14C]-Radioactivity Excreted in Faeces as Percentage of the Administered Oral Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe(Faeces,0-t2))	12.6 Percentage of dose excreted Geometric Coefficient of Variation 15.1	8.82 Percentage of dose excreted Geometric Coefficient of Variation 13.9

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at 2 hours (h) prior to drug administration and at 0.33, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 192, 240, 288, 336, 485, 653, 821, 989 and 1157 h after drug administration on Day 1.

Population: PKS

Cmax, maximum measured concentration of 14C-BI 1467335-Equivalence (EQ) in plasma after single oral administration of \[14C\]BI 1467335 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Maximum Measured Concentration of 14C-BI 1467335-Equivalence (EQ) in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax)	503.0 nanomole/ Liter (nmol/L) Geometric Coefficient of Variation 12.7	—

SECONDARY outcome

Population: PKS

AUC0-tz, area under the concentration-time curve of 14C-BI 1467335-Equivalence(EQ) over the time interval from 0 to the last quantifiable time point in plasma after single oral administration of \[14C\]BI 1467335 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Area Under the Concentration-time Curve of 14C-BI 1467335-Equivalence (EQ) Over the Time Interval From 0 to the Last Quantifiable Time Point in Plasma After Single Oral Administration of [14C]BI 1467335 (AUC0-tz)	72900.0 nanomole * hour/Liter (nmol*h/L) Geometric Coefficient of Variation 18.1	—

SECONDARY outcome

Population: PKS

Cmax, maximum measured concentration of BI 1467335 in plasma after single oral administration of \[14C\]BI 1467335 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Maximum Measured Concentration of BI 1467335 in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax)	2.88 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 146.00	—

SECONDARY outcome

Population: PKS

AUC0-tz, area under the concentration-time curve of BI 1467335 over the time interval from 0 to the last quantifiable time point in plasma after single oral administration of \[14C\]BI 1467335 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 to the Last Quantifiable Time Point in Plasma After Single Oral Administration of [14C]BI 1467335 (AUC0-tz)	2.97 nanomole * hour/Liter (nmol*h/L) Geometric Coefficient of Variation 128.00	—

SECONDARY outcome

Timeframe: PK samples were collected at 2 hours (h) prior dosing and at 646, 648:33, 648:75, 649, 650, 651, 652, 654, 656, 658, 660, 672, 684, 696, 720, 744, 768, 792, 816, 817, 864, 912, 936, 937, 960, 1008, 1181, 1349, 1517, 1685 and 1853 h after dosing on Day 1.

Population: PKS

Maximum measured concentration of 14C-BI 1467335-Equivalence (EQ) (Cmax) on Day 28 following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg \[14C\]BI 1467335 on day 28 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Maximum Measured Concentration of 14C-BI 1467335-Equivalence (EQ) (Cmax) on Day 28 Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	347.0 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 16.5	—

SECONDARY outcome

Population: PKS

Area under the concentration-time curve of 14C-BI 1467335-Equivalence (EQ) in plasma following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg \[14C\]BI 1467335 on day 28 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Area Under the Concentration-time Curve of 14C-BI 1467335-Equivalence (EQ) in Plasma Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	67400.00 nanomole * hour/ Liter (nmol*h/L) Geometric Coefficient of Variation 7.58	—

SECONDARY outcome

Population: PKS

Maximum measured concentration of BI 1467335 (Cmax) on Day 28 following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg \[14C\]BI 1467335 on day 28 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Maximum Measured Concentration of BI 1467335 (Cmax) on Day 28 Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	69.6 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 65.0	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected at 2 hours (h) prior to drug administration and at 646, 648:33, 648:75, 649, 650, 651, 652, 654, 656, 658, 660, 672 h after drug administration on Day 1.

Population: PKS

Area under the concentration time-curve of BI 1467335 on Day 28 over the time interval 24 h following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg \[14C\]BI 1467335 on day 28 is presented.

Outcome measures

Outcome measures
Measure	BI 1467335 10 Milligram (mg) (SD) n=8 Participants Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	BI 1467335 10 mg (MD) Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Area Under the Concentration Time-curve of BI 1467335 on Day 28 Over the Time Interval 24 h Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	268.00 nanomole * hour/Liter (nmol *h/L) Geometric Coefficient of Variation 123.00	—

Adverse Events

BI 1467335 10 mg (MD)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

BI 1467335 10 Milligram (mg) (SD)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Boehringer Ingelheim, Call Centre

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	BI 1467335 10 mg (MD) n=8 participants at risk Participants were administered once daily 10 mg (2\*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.	BI 1467335 10 Milligram (mg) (SD) n=8 participants at risk Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.
Infections and infestations Nasopharyngitis	75.0% 6/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	25.0% 2/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Nervous system disorders Headache	50.0% 4/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Nervous system disorders Somnolence	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	25.0% 2/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Nervous system disorders Dizziness	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Nervous system disorders Paraesthesia	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Musculoskeletal and connective tissue disorders Arthralgia	25.0% 2/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Musculoskeletal and connective tissue disorders Back pain	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Musculoskeletal and connective tissue disorders Myalgia	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Musculoskeletal and connective tissue disorders Neck pain	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Skin and subcutaneous tissue disorders Dry skin	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	37.5% 3/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	25.0% 2/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Skin and subcutaneous tissue disorders Eczema	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Gastrointestinal disorders Abdominal distension	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	25.0% 2/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Gastrointestinal disorders Abdominal discomfort	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Gastrointestinal disorders Constipation	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
General disorders Catheter site inflammation	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
General disorders Fatigue	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
General disorders Feeling cold	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
General disorders Influenza like illness	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
General disorders Medical device site reaction	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
General disorders Vessel puncture site haematoma	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Respiratory, thoracic and mediastinal disorders Cough	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Respiratory, thoracic and mediastinal disorders Throat irritation	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Eye disorders Eye irritation	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Psychiatric disorders Insomnia	12.5% 1/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.	0.00% 0/8 • From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group. Treated set (TS): This set included all participants who received at least 1 dose of trial medication.