This Study in Healthy Men Tests How Different Doses of BI 894416 Are Taken up in the Body and How Well BI 894416 is Tolerated

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 894416 in Healthy Male Subjects (Single-blind, Partially Randomised, Placebo-controlled Parallel Group Design)

This first-in man trial is designed to investigate the safety and tolerability of BI 894416 in healthy male subjects following oral administration of single rising doses.

Pharmacokinetics (PK) including dose proportionality after single dosing of BI 894416 as oral solution will be explored, the investigation of PK of BI 894416 as tablet formulation and the exploration of relative bioavailability of BI 894416 as tablet formulation compared to oral solution.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 894416; Drug: BI 894416

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male subjects according to the assessment of the investigator, 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) and including the neurological examination) 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 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 than 30 g per day)
• 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:

• History of relevant neurological disorder affecting the peripheral or central nervous system (this includes, but is not limited to: stroke, epilepsy, inflammatory or atrophic diseases affecting the nervous system, cluster headache or any cancer of the nervous system)
• History of immunological disease except allergy not relevant to the trial (such as mild hay fever or dust mite allergy) and except asthma in childhood or adolescence
• History of cancer (other than successfully treated basal cell carcinoma)
• Within 10 days prior to administration of trial medication, use of any drug that could reasonably inhibit platelet aggregation or coagulation (e.g., acetylsalicylic acid)
• Male subjects with woman of child bearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of administration of trial medication until 30 days thereafter.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo matching BI 894416 (SRD Part); Single Rising Dose (SRD) Part	Drug: Placebo; Oral solution
Experimental: BI 894416 3 milligram (mg); SRD Part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 10 mg; SRD Part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 20 mg; SRD Part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 30 mg; SRD Part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 40 mg; SRD Part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 54 mg; SRD Part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 70 mg; SRD Part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 10mg tb / 10mg PfOS / 40mg tb; BI 894416 10 mg tablet (tb) / BI 894416 10 mg powder for oral solution (PfOS) / BI 894416 4*10 mg tablets. Relative bioavailability (rel BA) part	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution
Experimental: BI 894416 10mg PfOS / 10mg tb / 40mg tb; BI 894416 10 mg powder for oral solution (PfOS) / BI 894416 10 mg tablet (tb) / BI 894416 4*10 mg tablets. Relative bioavailability (rel BA) part.	Drug: BI 894416; Tablet; Drug: BI 894416; powder for oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Drug-related Adverse Events in SRD Part	Percentage of participants with drug-related adverse events (AEs) in SRD part. Percentages are calculated using total number of subjects per treatment as the denominator. Percentages were rounded up to 1 decimal places.	From drug administration until end of the trial, up to 17 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part	Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) in SRD part is presented.	Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 168 h after drug administration.
Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part	Maximum measured concentration of BI 894416 in plasma (Cmax) in SRD part is presented.	Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 168 h after drug administration.
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) in Rel BA Part	Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in rel BA part is presented. "BI 894416 40 mg tb" arm was compared in a descriptive fashion with other dose groups without statistical analysis.	Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration.
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in Rel BA Part	Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) in rel BA part is presented. "BI 894416 40 mg tb" arm was compared in a descriptive fashion with other dose groups without statistical analysis.	Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration.
Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in Rel BA Part	Maximum measured concentration of BI 894416 in plasma (Cmax) in rel BA part is presented. "BI 894416 40 mg tb" arm was compared in a descriptive fashion with other dose groups without statistical analysis.	Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2017
• Primary Completion (Actual): September 10, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: October 17, 2017
• First Submitted That Met QC Criteria: October 17, 2017
• First Posted (Actual): October 20, 2017

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 1371-0001; 2016-003470-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No