CompletedNCT03004404Updated Aug 16, 2023Results posted

To Assess Safety, Tolerability and Pharmacokinetics of BI 730357 in Healthy Male Volunteers

A Phase 1 interventional study of Placebo and BI 730357 in Healthy Volunteers, sponsored by Boehringer Ingelheim. Completed at 1 site in Germany. Open to male participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-08-16.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 84
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: Male

Study summary

The primary objective of the Single Rising Dose (SRD) part (trial part 1) is to investigate the safety and tolerability of BI 730357 in healthy subjects following oral administration of single rising doses after fasting and/or non-fasting conditions. The secondary objective is the exploration of the pharmacokinetics (PK) including dose proportionality, and pharmacodynamics of BI 730357 after single dosing.

The objective of the Bioavailability (BA) part (trial part 2) will be to explore the relative bioavailability of tablet fasted versus oral solution fasted and the influence of food on the bioavailability of tablet fasted versus tablet fed.

Conditions studied

Healthy Volunteers

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: Male
Accepts healthy volunteers: Yes

Inclusion criteria

Healthy male according to the Investigator's assessment, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
Age of 18 to 45 years (incl.)
Body Mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria

Exclusion Criteria:

Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the Investigator
Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
Any laboratory value outside the reference range that the Investigator considers to be of clinical relevance
Any evidence of a concomitant disease judged as clinically relevant by the Investigator
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
History of relevant orthostatic hypotension, fainting spells, or blackouts
Chronic or relevant acute infections
History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc (corrected QT) interval prolongation)
Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
Inability to refrain from smoking on specified trial days
Alcohol abuse (consumption of more 30 g per day for males)
Drug abuse or positive drug screening
Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
Inability to comply with dietary regimen of trial site
A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
Subject is assessed as unsuitable for inclusion by the Investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

In addition, the following trial-specific exclusion criteria apply:

Male subjects with Women of childbearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Single (Participant)
Enrollment: 84 participants (actual)

Study arms

Experimental
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.
Drug: BI 730357
Placebo comparator
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.
Drug: Placebo
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
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.
Drug: BI 730357
Experimental
BA Part: T1/T2/R
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.
Drug: BI 730357

Interventions

DrugPlacebo
Placebo
DrugBI 730357
powder for reconstitution of an oral solution (PfoS)
DrugBI 730357
BI 730357 film-coated tablet

What researchers measure

Primary outcomes

Percentage of Subjects With Drug-related Adverse Events (AEs)
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.
Time frame: 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.

Secondary outcomes

Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
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.
Time frame: 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
Maximum Measured Concentration of BI 730357 in Plasma (Cmax)
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.
Time frame: 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

Results

Posted Aug 16, 2023

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.

Period 1

Participant flow — Period 1
Milestone	Placebo	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part: R/T2/T1	BA Part: R/T1/T2	BA Part: T2/R/T1	BA Part: T2/T1/R	BA Part: T1/R/T2	BA Part: T1/T2/R
Started	18	6	6	6	6	6	6	6	6	6	2	2	2	2	2	2
Completed	18	6	6	6	6	6	6	6	6	6	2	2	2	2	2	2
Not completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Period 2

Participant flow — Period 2
Milestone	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed	BA Part: R/T2/T1	BA Part: R/T1/T2	BA Part: T2/R/T1	BA Part: T2/T1/R	BA Part: T1/R/T2	BA Part: T1/T2/R
Started	6	2	2	2	2	2	2
Completed	5	2	2	2	2	2	1
Not completed	1	0	0	0	0	0	1
Withdrew: Adverse event	1	0	0	0	0	0	1

Period 3

Participant flow — Period 3
Milestone	BA Part: R/T2/T1	BA Part: R/T1/T2	BA Part: T2/R/T1	BA Part: T2/T1/R	BA Part: T1/R/T2	BA Part: T1/T2/R
Started	2	2	2	2	2	1
Completed	2	2	2	2	2	1
Not completed	0	0	0	0	0	0

Outcome measures

PrimaryPercentage of Subjects With Drug-related Adverse Events (AEs)

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.

Time frame:: 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.
Reported as:: Number · Percentage of participants

Percentage of Subjects With Drug-related Adverse Events (AEs)
Percentage of participants	Placebo	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1	SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part: BI 730357 Tablet 25 mg Fasted (R)	BA Part: BI 730357 PfOS 25 mg Fasted (T1)	BA Part: BI 730357 Tablet 25 mg Fed (T2)
Percentage of Subjects With Drug-related Adverse Events (AEs)	5.6	0.0	16.7	0.0	0.0	16.7	16.7	0.0	0.0	20.0	0.0	0.0	0.0	0.0

SecondaryArea Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)

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.

Time frame:: 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
Reported as:: Geometric mean · nanomol*hour/liter (nmol*h/L)

Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
nanomolhour/liter (nmolh/L)	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1	SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part: BI 730357 Tablet 25 mg Fasted (R)	BA Part: BI 730357 PfOS 25 mg Fasted (T1)	BA Part: BI 730357 Tablet 25 mg Fed (T2)
Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)	399.0 ± 35.0	1550.0 ± 27.8	3730.0 ± 36.4	6990.0 ± 52.7	10700.0 ± 60.2	18300.0 ± 28.0	30800.0 ± 36.8	44800.0 ± 41.5	50700.0 ± 57.5	77900.0 ± 38.3	4240.0 ± 45.0	5390.0 ± 43.8	5370.0 ± 44.6

Statistical analysis

SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted vs SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted vs SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted vs SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted vs SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted · Slope: 0.7480 · 95% CI 0.5959 to 0.9001Standard error of the mean is actually standard error of the slope. Based on the estimate for the slope parameter, a two sided 95% confidence interval for the slope was computed. Perfect dose proportionality would correspond to a slope of 1.
SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1 vs SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2 · Ratio t/r: 118.71 · 90% CI 94.57 to 149.03Standard error of the mean is the geometric standard error of the mean. The geometric mean ratio was calculated as: tablet 400mg fed1 (T)/400mg fed2(R), T/R.
BA Part: BI 730357 Tablet 25 mg Fasted (R) vs BA Part: BI 730357 PfOS 25 mg Fasted (T1) · Geometric mean ratio t1/r (%): 124.79 · 90% CI 116.858 to 133.255Standard error of the mean is actually geometric standard error of the mean. The geometric mean ratio was calculated as: oral solution in fasted state (test treatment T1)/tablet in fasted state (reference treatment R), T1/R.
BA Part: BI 730357 Tablet 25 mg Fasted (R) vs BA Part: BI 730357 Tablet 25 mg Fed (T2) · Geometric mean ratio t2/r (%): 125.17 · 90% CI 112.89 to 138.80Standard error of the mean is actually geometric standard error of the mean. The geometric mean ratio was calculated as: tablet in fed state (test treatment T2)/tablet in fasted state (reference treatment R), T2/R.

SecondaryMaximum Measured Concentration of BI 730357 in Plasma (Cmax)

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.

Time frame:: 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
Reported as:: Geometric mean · nanomol / liter (nmol/L)

Maximum Measured Concentration of BI 730357 in Plasma (Cmax)
nanomol / liter (nmol/L)	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1	SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part: BI 730357 Tablet 25 mg Fasted (R)	BA Part: BI 730357 PfOS 25 mg Fasted (T1)	BA Part: BI 730357 Tablet 25 mg Fed (T2)
Maximum Measured Concentration of BI 730357 in Plasma (Cmax)	32.9 ± 39.4	154.0 ± 28.9	103.0 ± 31.7	173.0 ± 41.9	284.0 ± 30.7	433.0 ± 27.6	755.0 ± 37.4	1270.0 ± 17.5	1900.0 ± 30.2	2470.0 ± 15.7	133.0 ± 31.4	380.0 ± 27.4	235.0 ± 28.5

Statistical analysis

SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted vs SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted vs SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted vs SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted vs SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted · Slope: 0.7065 · 95% CI 0.5863 to 0.8267Standard error of the mean is actually standard error of the slope. Based on the estimate for the slope parameter, a two sided 95% confidence interval for the slope was computed. Perfect dose proportionality would correspond to a slope of 1
SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1 vs SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2 · Ratio t/r: 151.22 · 90% CI 122.781 to 186.248Standard error of the mean is the geometric standard error of the mean. The geometric mean ratio was calculated as: tablet 400mg fed1 (T)/400mg fed2(R), T/R.
BA Part: BI 730357 Tablet 25 mg Fasted (R) vs BA Part: BI 730357 PfOS 25 mg Fasted (T1) · Geometric mean ratio t1/r (%): 293.21 · 90% CI 259.044 to 331.891Standard error of the mean is the geometric standard error of the mean. The geometric mean ratio was calculated as: oral solution in fasted state (test treatment T1)/tablet in fasted state (reference treatment R), T1/R.
BA Part: BI 730357 Tablet 25 mg Fasted (R) vs BA Part: BI 730357 Tablet 25 mg Fed (T2) · Geometric mean ratio t2/r (%): 180.53 · 90% CI 162.369 to 200.732Standard error of the mean is the geometric standard error of the mean. The geometric mean ratio was calculated as: tablet in fed state (test treatment T2)/tablet in fasted state (reference treatment R), T2/R.

Adverse events

Collected over SRD 1-7, 9-10: From first drug administration until end of trial (EOT), up to 13 days. SRD 8: From first drug administration until end of trial (EOT), up to 14 days. BA per treatment: From first drug administration until end of trial (EOT), up to 14 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo	0/18 (0%)	0/18 (0%)	5/18 (27.8%)
SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	0/6 (0%)	0/6 (0%)	3/6 (50%)
SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	0/6 (0%)	0/6 (0%)	3/6 (50%)
SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	0/6 (0%)	0/6 (0%)	1/6 (16.7%)
SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	0/6 (0%)	0/6 (0%)	4/6 (66.7%)
SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	0/6 (0%)	0/6 (0%)	3/6 (50%)
SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2	0/5 (0%)	0/5 (0%)	3/5 (60%)
SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	0/6 (0%)	0/6 (0%)	1/6 (16.7%)
BA Part: BI 730357 Tablet 25 mg Fasted (R)	0/11 (0%)	0/11 (0%)	2/11 (18.2%)
BA Part: BI 730357 PfOS 25 mg Fasted (T1)	0/12 (0%)	0/12 (0%)	2/12 (16.7%)
BA Part: BI 730357 Tablet 25 mg Fed (T2)	0/12 (0%)	0/12 (0%)	3/12 (25%)

Most frequent other events

Showing 10 of 24

Most frequent other events
Event	Placebo	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1	SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part: BI 730357 Tablet 25 mg Fasted (R)	BA Part: BI 730357 PfOS 25 mg Fasted (T1)	BA Part: BI 730357 Tablet 25 mg Fed (T2)
Gastroenteritis viralInfections and infestations	0/18	0/6	0/6	0/6	0/6	0/6	0/6	0/6	2/6	0/5	0/6	0/11	0/12	0/12
HeadacheNervous system disorders	1/18	0/6	1/6	0/6	1/6	2/6	1/6	2/6	1/6	1/5	0/6	0/11	0/12	0/12
Burns second degreeInjury, poisoning and procedural complications	0/18	0/6	0/6	0/6	0/6	0/6	0/6	0/6	0/6	1/5	0/6	0/11	0/12	0/12
PetechiaeSkin and subcutaneous tissue disorders	0/18	0/6	0/6	0/6	0/6	0/6	0/6	0/6	0/6	1/5	0/6	0/11	0/12	0/12
RashSkin and subcutaneous tissue disorders	1/18	0/6	0/6	0/6	0/6	0/6	1/6	0/6	1/6	1/5	0/6	0/11	0/12	0/12
Abdominal discomfortGastrointestinal disorders	0/18	0/6	0/6	0/6	0/6	1/6	0/6	0/6	0/6	0/5	0/6	0/11	0/12	0/12
ToothacheGastrointestinal disorders	0/18	1/6	0/6	0/6	0/6	0/6	0/6	0/6	0/6	0/5	0/6	0/11	0/12	0/12
Medical device site rashGeneral disorders	0/18	0/6	0/6	0/6	0/6	0/6	0/6	0/6	1/6	0/5	0/6	0/11	0/12	0/12
Vessel puncture site haematomaGeneral disorders	0/18	0/6	0/6	0/6	1/6	0/6	0/6	0/6	0/6	0/5	0/6	0/11	0/12	0/12
Gastrointestinal infectionInfections and infestations	0/18	0/6	0/6	0/6	0/6	0/6	1/6	0/6	0/6	0/5	0/6	0/11	0/12	0/12

Baseline characteristics

Treated Set (TS): The Treated set (TS) included all subjects from the Randomised set (RS) who were documented to have taken at least 1 dose of trial medication. The TS for the SRD part included 72 subjects. The TS for the BA part included all 12 treated subjects.

Age, Continuous
Age, Continuous(Years)	Placebo	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part	Total
Mean	32.3 ± 6.3	36.8 ± 4.5	33.0 ± 6.5	30.7 ± 6.7	30.2 ± 8.7	31.3 ± 5.0	30.2 ± 7.9	34.5 ± 5.9	30.8 ± 7.0	31.7 ± 5.5	35.3 ± 8.6	32.6 ± 6.7

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part	Total
Female	0	0	0	0	0	0	0	0	0	0	0	0
Male	18	6	6	6	6	6	6	6	6	6	12	84

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part	Total
Hispanic or Latino	0	0	0	0	0	0	0	0	0	0	0	0
Not Hispanic or Latino	18	6	6	6	6	6	6	6	6	6	12	84
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Placebo	SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted	SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted	SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted	SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted	SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted	SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted	SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted	SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed	SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed	BA Part	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	1	0	0	0	0	0	0	0	0	0	0	1
White	17	6	6	6	6	6	6	6	6	6	12	83
More than one race	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0

Study locations

1 site

Humanpharmakologisches Zentrum Biberach
Biberach, 88397, Germany

References and documents

Study documents

Study protocol · May 5, 2017
Statistical analysis plan · Sep 22, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 16, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03004404
Lead sponsor: Boehringer Ingelheim
Responsible party: Sponsor
First posted: Dec 28, 2016
Start date: Jan 12, 2017
Primary completion: Aug 15, 2017
Completion: Aug 15, 2017
Results posted: Aug 16, 2023
Last update: Aug 16, 2023

Study contacts

Boehringer Ingelheim

study chair · Boehringer Ingelheim

View the source record on ClinicalTrials.gov ↗

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