Trial Outcomes & Findings for To Assess Safety, Tolerability and Pharmacokinetics of BI 730357 in Healthy Male Volunteers (NCT NCT03004404)

Last Updated: 2023-08-16

Results Overview

Percentage of subjects with adverse reactions, assessed by investigator-defined drug-related adverse events (AEs) are reported. Fed1 means intake of continental breakfast; fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same participants.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

84 participants

Primary outcome timeframe

SRD 1-7, 10: From first drug administration until end of trial (EOT), up to 13 days. SRD 8-9: From first drug administration until end of trial (EOT), up to 27 days. BA: From first drug administration until end of trial (EOT), up to 41 days.

Results posted on

2023-08-16

Participant Flow

This study had two parts, single rising dose (SRD): partially randomized, single-blind, placebo-controlled, parallel group design to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 730357. Bioavailability/food effect (BA/FE) part: Single dose, randomised, open-label, intra-individual three-way crossover to investigate the relative BA of the tablet formulation versus oral solution as well as the influence of food on the bioavailability of the tablet formulation.

All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated.

Participant milestones

Participant milestones
Measure	Placebo This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants of the first cohort of each dose group (DG) were not randomized. In the second cohort of each DG participants were assigned to active treatment or placebo in a 3:1 allocation ratio. Participants were administered on Day 1 a single oral dose of matching placebo, for dose group (DG) 1-2 the matching placebo was solvent for oral solution containing Macrogol 400 (Polyethylene glycol 400) on a volume identical to dose group of active treatment, for DG 3-7 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fasted state. For DG 8-10 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fed state, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast/continental breakfast depending on dose group. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted Participants were administered on Day 1 a single oral dose of 2 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 2 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted Participants were administered on Day 1 a single oral dose of 8 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 8 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted Participants were administered on Day 1 a single oral dose of 25 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted Participants were administered on Day 1 a single oral dose of 50 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 730357 film-coated tablets (2x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (4x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed The same participants conformed the Dose group (DG) 8 and DG 9. DG 8: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard continental breakfast. DG 9: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. Both treatment periods were separated by a wash-out phase of at least 14 days between drug administration of DG 8 and DG 9. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (16x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: R/T2/T1 Participants were orally administered 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Followed by 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: R/T1/T2 Participants were orally administered 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Followed by 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T2/R/T1 Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T2/T1/R Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T1/R/T2 Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T1/T2/R Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.
Period 1 STARTED	18	6	6	6	6	6	6	6	6	6	2	2	2	2	2	2
Period 1 COMPLETED	18	6	6	6	6	6	6	6	6	6	2	2	2	2	2	2
Period 1 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period 2 STARTED	0	0	0	0	0	0	0	0	6	0	2	2	2	2	2	2
Period 2 COMPLETED	0	0	0	0	0	0	0	0	5	0	2	2	2	2	2	1
Period 2 NOT COMPLETED	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Period 3 STARTED	0	0	0	0	0	0	0	0	0	0	2	2	2	2	2	1
Period 3 COMPLETED	0	0	0	0	0	0	0	0	0	0	2	2	2	2	2	1
Period 3 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants of the first cohort of each dose group (DG) were not randomized. In the second cohort of each DG participants were assigned to active treatment or placebo in a 3:1 allocation ratio. Participants were administered on Day 1 a single oral dose of matching placebo, for dose group (DG) 1-2 the matching placebo was solvent for oral solution containing Macrogol 400 (Polyethylene glycol 400) on a volume identical to dose group of active treatment, for DG 3-7 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fasted state. For DG 8-10 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fed state, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast/continental breakfast depending on dose group. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted Participants were administered on Day 1 a single oral dose of 2 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 2 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted Participants were administered on Day 1 a single oral dose of 8 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 8 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted Participants were administered on Day 1 a single oral dose of 25 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted Participants were administered on Day 1 a single oral dose of 50 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 730357 film-coated tablets (2x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (4x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed The same participants conformed the Dose group (DG) 8 and DG 9. DG 8: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard continental breakfast. DG 9: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. Both treatment periods were separated by a wash-out phase of at least 14 days between drug administration of DG 8 and DG 9. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (16x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: R/T2/T1 Participants were orally administered 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Followed by 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: R/T1/T2 Participants were orally administered 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Followed by 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T2/R/T1 Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T2/T1/R Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T1/R/T2 Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: T1/T2/R Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) in fasted state. Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2), a high-fat, high-calorie breakfast was served 30 min before dose administration. Followed by 25 mg of BI 730357 as film-coated tablet (Reference treatment R) in fasted state. The 3 treatments were administered with 240 mL of water and were separated by a washout period of at least 8 days. One authorized employee of the trial site was witness of the administration of the trial medication.
Period 2 Adverse Event	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1

Baseline Characteristics

Treated Set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=18 Participants This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants of the first cohort of each dose group (DG) were not randomized. In the second cohort of each DG participants were assigned to active treatment or placebo in a 3:1 allocation ratio. Participants were administered on Day 1 a single oral dose of matching placebo, for dose group (DG) 1-2 the matching placebo was solvent for oral solution containing Macrogol 400 (Polyethylene glycol 400) on a volume identical to dose group of active treatment, for DG 3-7 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fasted state. For DG 8-10 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fed state, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast/continental breakfast depending on dose group. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 2 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 2 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 8 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 8 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 25 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 50 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 730357 film-coated tablets (2x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (4x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed n=6 Participants The same participants conformed the Dose group (DG) 8 and DG 9. DG 8: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard continental breakfast. DG 9: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. Both treatment periods were separated by a wash-out phase of at least 14 days between drug administration of DG 8 and DG 9. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (16x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part n=12 Participants In the BA part of the trial, subjects were randomised to 6 treatment sequences. All subjects were administered BI 730357 as tablet in fasted condition (R), as oral solution in fasted condition (T1), and as tablet after a standardised high-fat breakfast (T2). The 3 treatments were separated by a wash-out period of at least 8 days between trial drug administrations. One authorized employee of the trial site was witness of the administration of the trial medication.	Total n=84 Participants Total of all reporting groups
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • Treated Set	0 Participants n=7 Participants • Treated Set	0 Participants n=5 Participants • Treated Set	0 Participants n=4 Participants • Treated Set	0 Participants n=21 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=24 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set
Age, Continuous	32.3 Years STANDARD_DEVIATION 6.3 • n=5 Participants • Treated set	36.8 Years STANDARD_DEVIATION 4.5 • n=7 Participants • Treated set	33.0 Years STANDARD_DEVIATION 6.5 • n=5 Participants • Treated set	30.7 Years STANDARD_DEVIATION 6.7 • n=4 Participants • Treated set	30.2 Years STANDARD_DEVIATION 8.7 • n=21 Participants • Treated set	31.3 Years STANDARD_DEVIATION 5.0 • n=8 Participants • Treated set	30.2 Years STANDARD_DEVIATION 7.9 • n=8 Participants • Treated set	34.5 Years STANDARD_DEVIATION 5.9 • n=24 Participants • Treated set	30.8 Years STANDARD_DEVIATION 7.0 • n=42 Participants • Treated set	31.7 Years STANDARD_DEVIATION 5.5 • n=42 Participants • Treated set	35.3 Years STANDARD_DEVIATION 8.6 • n=42 Participants • Treated set	32.6 Years STANDARD_DEVIATION 6.7 • n=42 Participants • Treated set
Sex: Female, Male Female	0 Participants n=5 Participants • Treated Set	0 Participants n=7 Participants • Treated Set	0 Participants n=5 Participants • Treated Set	0 Participants n=4 Participants • Treated Set	0 Participants n=21 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=24 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set
Sex: Female, Male Male	18 Participants n=5 Participants • Treated Set	6 Participants n=7 Participants • Treated Set	6 Participants n=5 Participants • Treated Set	6 Participants n=4 Participants • Treated Set	6 Participants n=21 Participants • Treated Set	6 Participants n=8 Participants • Treated Set	6 Participants n=8 Participants • Treated Set	6 Participants n=24 Participants • Treated Set	6 Participants n=42 Participants • Treated Set	6 Participants n=42 Participants • Treated Set	12 Participants n=42 Participants • Treated Set	84 Participants n=42 Participants • Treated Set
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	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	6 Participants n=8 Participants	6 Participants n=8 Participants	6 Participants n=24 Participants	6 Participants n=42 Participants	6 Participants n=42 Participants	12 Participants n=42 Participants	84 Participants n=42 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	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants • Treated Set	0 Participants n=7 Participants • Treated Set	0 Participants n=5 Participants • Treated Set	0 Participants n=4 Participants • Treated Set	0 Participants n=21 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=24 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • Treated Set	0 Participants n=7 Participants • Treated Set	0 Participants n=5 Participants • Treated Set	0 Participants n=4 Participants • Treated Set	0 Participants n=21 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=24 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants • Treated Set	0 Participants n=7 Participants • Treated Set	0 Participants n=5 Participants • Treated Set	0 Participants n=4 Participants • Treated Set	0 Participants n=21 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=24 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	1 Participants n=42 Participants • Treated Set
Race (NIH/OMB) White	17 Participants n=5 Participants • Treated Set	6 Participants n=7 Participants • Treated Set	6 Participants n=5 Participants • Treated Set	6 Participants n=4 Participants • Treated Set	6 Participants n=21 Participants • Treated Set	6 Participants n=8 Participants • Treated Set	6 Participants n=8 Participants • Treated Set	6 Participants n=24 Participants • Treated Set	6 Participants n=42 Participants • Treated Set	6 Participants n=42 Participants • Treated Set	12 Participants n=42 Participants • Treated Set	83 Participants n=42 Participants • Treated Set
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • Treated Set	0 Participants n=7 Participants • Treated Set	0 Participants n=5 Participants • Treated Set	0 Participants n=4 Participants • Treated Set	0 Participants n=21 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=24 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Treated Set	0 Participants n=7 Participants • Treated Set	0 Participants n=5 Participants • Treated Set	0 Participants n=4 Participants • Treated Set	0 Participants n=21 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=8 Participants • Treated Set	0 Participants n=24 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set	0 Participants n=42 Participants • Treated Set

PRIMARY outcome

Timeframe: SRD 1-7, 10: From first drug administration until end of trial (EOT), up to 13 days. SRD 8-9: From first drug administration until end of trial (EOT), up to 27 days. BA: From first drug administration until end of trial (EOT), up to 41 days.

Population: Treated set (TS): This subject set included all subjects from the Randomised set (RS) who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants of the first cohort of each dose group (DG) were not randomized. In the second cohort of each DG participants were assigned to active treatment or placebo in a 3:1 allocation ratio. Participants were administered on Day 1 a single oral dose of matching placebo, for dose group (DG) 1-2 the matching placebo was solvent for oral solution containing Macrogol 400 (Polyethylene glycol 400) on a volume identical to dose group of active treatment, for DG 3-7 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fasted state. For DG 8-10 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fed state, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast/continental breakfast depending on dose group. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 2 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 2 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 8 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 8 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 25 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 50 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 730357 film-coated tablets (2x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (4x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1 n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard continental breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2 n=5 Participants Participants were administered on Day 1 of period 2 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (16x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: BI 730357 Tablet 25 mg Fasted (R) n=11 Participants Participants were orally administered 25 mg of BI 730357 as film-coated tablet (Reference treatment R) together with about 240 mL of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: BI 730357 PfOS 25 mg Fasted (T1) n=12 Participants Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) together with about 240 mL of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: BI 730357 Tablet 25 mg Fed (T2) n=12 Participants Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2) together with about 240 mL of water, a high-fat, high-calorie breakfast was served 30 min before dose administration. One authorized employee of the trial site was witness of the administration of the trial medication.
Percentage of Subjects With Drug-related Adverse Events (AEs)	5.6 Percentage of participants	0.0 Percentage of participants	16.7 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	16.7 Percentage of participants	16.7 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	20.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: SRD & BA Part: Within 3 hours (h) prior administration, and 0.5h, 1.0h, 1.5h, 2.0h, 2.5h, 3.0h, 4.0h, 5.0h, 6.0h, 8.0h, 10.0h, 12.0h, 24.0h, 34.0h, 48.0h, 72.0h, 96.0h and 168.0h after drug administration

Population: Pharmacokinetic set (PKS): The PKS included all subjects who were treated with BI 730357 and who provided at least 1 secondary PK endpoint (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.

Area under the concentration-time curve of BI 730357 in plasma over the time interval from 0 extrapolated to infinity is reported. Fed1 means intake of continental breakfast; fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same subjects.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants of the first cohort of each dose group (DG) were not randomized. In the second cohort of each DG participants were assigned to active treatment or placebo in a 3:1 allocation ratio. Participants were administered on Day 1 a single oral dose of matching placebo, for dose group (DG) 1-2 the matching placebo was solvent for oral solution containing Macrogol 400 (Polyethylene glycol 400) on a volume identical to dose group of active treatment, for DG 3-7 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fasted state. For DG 8-10 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fed state, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast/continental breakfast depending on dose group. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 2 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 2 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 8 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 8 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 25 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 50 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 730357 film-coated tablets (2x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (4x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted n=6 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1 n=5 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard continental breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2 n=6 Participants Participants were administered on Day 1 of period 2 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed n=11 Participants Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (16x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: BI 730357 Tablet 25 mg Fasted (R) n=12 Participants Participants were orally administered 25 mg of BI 730357 as film-coated tablet (Reference treatment R) together with about 240 mL of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: BI 730357 PfOS 25 mg Fasted (T1) n=12 Participants Participants received 25 mg of BI 730357 powder for reconstitution of an oral solution (PfOS) reconstituted in solvent for oral solution 2.5 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) (test treatment T1) together with about 240 mL of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication.	BA Part: BI 730357 Tablet 25 mg Fed (T2) Participants were orally administered 25 mg of BI 730357 film-coated tablet in a fed state (test treatment T2) together with about 240 mL of water, a high-fat, high-calorie breakfast was served 30 min before dose administration. One authorized employee of the trial site was witness of the administration of the trial medication.
Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)	399.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 35.0	1550.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 27.8	3730.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 36.4	6990.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 52.7	10700.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 60.2	18300.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 28.0	30800.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 36.8	44800.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 41.5	50700.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 57.5	77900.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 38.3	4240.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 45.0	5390.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 43.8	5370.0 nanomolhour/liter (nmolh/L) Geometric Coefficient of Variation 44.6	—

SECONDARY outcome

Maximum measured concentration of BI 730357 in plasma is reported. Fed1 means intake of continental breakfast; Fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same subjects.