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

NCT ID: NCT03004404

Last Updated: 2023-08-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-12

Study Completion Date

2017-08-15

Brief Summary

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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.

Detailed Description

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Conditions

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Healthy Volunteers

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

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.

Group Type EXPERIMENTAL

BI 730357

Intervention Type DRUG

powder for reconstitution of an oral solution (PfoS)

BI 730357

Intervention Type DRUG

BI 730357 film-coated tablet

Interventions

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Placebo

Placebo

Intervention Type DRUG

BI 730357

powder for reconstitution of an oral solution (PfoS)

Intervention Type DRUG

BI 730357

BI 730357 film-coated tablet

Intervention Type DRUG

Eligibility Criteria

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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

* 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


\- 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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Humanpharmakologisches Zentrum Biberach

Biberach, , Germany

Site Status

Countries

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Germany

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2016-003047-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1407.1

Identifier Type: -

Identifier Source: org_study_id

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