This Study in Healthy Men Tests How Different Doses of BI 1358894 Are Taken up in the Body and How Well They Are Tolerated. The Study Also Looks at How Food Influences the Amount of BI 1358894 in the Blood

Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 1358894 in Healthy Male Subjects (Single-blind, Partially Randomised, Placebo-controlled Parallel Group Design) and Effect of Food on the Relative Bioavailability of BI 1358894 (Open-label, Randomised, Two-way Cross-over)

The primary objective of this trial is to investigate the safety and tolerability of BI 1358894 in healthy male subjects following oral administration of single rising doses. Secondary objectives are the exploration of the pharmacokinetics (PK), including dose proportionality of BI 1358894 after single dosing.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 1358894; Drug: BI 1358894 (Test); Drug: BI 1358894 (Reference)

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany, 68167
    • CRS Clinical Research Services Mannheim GmbH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy male according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Age of 18 to 45 years (incl.)
• 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 GCP and local legislation

• Willingness to comply with contraception requirements. Subjects who are sexually active, must use, with their female partner, adequate contraception throughout the study and until one month after the last administration of trial medication. Adequate methods are:

  • Sexual abstinence or
  • A vasectomy performed at least 1 year prior to screening in combination with a barrier method (condom) or
  • Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subjects female partner or
  • The use of condoms, if the female partner uses in addition an adequate contraception method, e.g., intrauterine device (IUD), hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g. diaphragm with spermicide)
• Unprotected sexual intercourse with a pregnant female partner is not allowed throughout the study and until one month after the last administration of trial medication

Exclusion Criteria:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal
• 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 bpm
• C-Reactive Protein > ULN, erythrocyte sedimentation rate (ESR) ≥ 15 millimeters/hour, liver and kidney parameter above ULN, other laboratory values outside the reference range 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 30 g per day for males)
• Drug abuse as per investigator judgment 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 in males) 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
• Any lifetime history of suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
• Any suicidal ideation of type 2 to 5 on the C-SSRS in the past 12 months (i.e. active suicidal thought, active suicidal thought with method, active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single rising dose part; Group of healthy male volunteers receive rising single doses of BI 1358894	Drug: Placebo; Tablet; Drug: BI 1358894; Tablet
EXPERIMENTAL: Food effect part; Group of healthy male volunteers receive single doses of BI 1358894 with and without food	Drug: BI 1358894 (Test); Fasting state; Drug: BI 1358894 (Reference); Fed state

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number [N (%)] of subjects with drug- related adverse event	Up to 14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data time point tz)	Up to 192 hours
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	Up to 192 hours
Cmax (maximum measured concentration of the analyte in plasma)	Up to 192 hours

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2017
• Primary Completion (ACTUAL): February 18, 2019
• Study Completion (ACTUAL): February 18, 2019

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 5, 2017
• First Posted (ACTUAL): July 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 20, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 1402-0001; 2017-000143-40 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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