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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: BI 894416

Study type: Interventional

Funder types: Industry

Identifiers

NCT03315936

2016-003470-40 (EudraCT Number)

1371-0001

Details and patient eligibility

About

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.

Enrollment: 68 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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68 participants in 10 patient groups, including a placebo group

Placebo matching BI 894416 (SRD Part)

Placebo Comparator group

Description:

Single Rising Dose (SRD) Part

Treatment:

Drug: Placebo

BI 894416 3 milligram (mg)

Experimental group

Description:

SRD Part

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 10 mg

Experimental group

Description:

SRD Part

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 20 mg

Experimental group

Description:

SRD Part

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 30 mg

Experimental group

Description:

SRD Part

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 40 mg

Experimental group

Description:

SRD Part

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 54 mg

Experimental group

Description:

SRD Part

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 70 mg

Experimental group

Description:

SRD Part

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 10mg tb / 10mg PfOS / 40mg tb

Experimental group

Description:

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

Treatment:

Drug: BI 894416

Drug: BI 894416

BI 894416 10mg PfOS / 10mg tb / 40mg tb

Experimental group

Description:

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.

Treatment:

Drug: BI 894416

Drug: BI 894416