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 Tests How BI 1358894 Affects the Way the Body Breaks Down Midazolam

Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 1358894 (Double-blind, Randomised, Placebo-controlled, Parallel-group Design) and Evaluation of Midazolam Interaction (Nested, Open, Fixed-sequence, Intra-individual Comparison) in Healthy Male Subjects

The primary objective of the trial is to investigate the safety and tolerability of BI 1358894 in healthy male subjects following oral administration of multiple rising doses over 14 days.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 1358894; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 50
• 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 subjects 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

• Willingness to comply with contraception requirements. Subjects who are sexually active must use adequate contraception with their female partner 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 (with medical assessment of the surgical success) or
  • Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner or
  • The use of condoms, if the female partner uses an adequate contraception method in addition, 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 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 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)
• C-Reactive Protein > upper limit of normal (ULN), erythrocyte sedimentation rate (ESR) ≥15 millimeters/h, liver or kidney parameter above ULN, or any other laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Positive or missing faecal occult blood test (retest allowed)
• Positive testing for faecal calprotectin (retest allowed)
• 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 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 during in-house confinement
• 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 Electrocardiogram (ECG) finding at screening
• A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalaemia, 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose Group 1	Drug: Placebo; Film-coated tablet; Drug: BI 1358894; Film-coated tablet; Drug: Midazolam; Solution for injection
EXPERIMENTAL: Dose Group 2	Drug: Placebo; Film-coated tablet; Drug: BI 1358894; Film-coated tablet; Drug: Midazolam; Solution for injection
EXPERIMENTAL: Dose Group 3	Drug: Placebo; Film-coated tablet; Drug: BI 1358894; Film-coated tablet; Drug: Midazolam; Solution for injection
EXPERIMENTAL: Dose Group 4	Drug: Placebo; Film-coated tablet; Drug: BI 1358894; Film-coated tablet; Drug: Midazolam; Solution for injection
EXPERIMENTAL: Dose Group 5	Drug: Placebo; Film-coated tablet; Drug: BI 1358894; Film-coated tablet; Drug: Midazolam; Solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with on-treatment drug-related AEs	up to 32 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of BI 1358894 in plasma over a time interval 0 to 24 h after administration of the first dose	up to 24 hours
Maximum measured concentration of BI 1358894 in plasma	up to 32 days
Area under the concentration-time curve of BI 1358894 in plasma at steady state over a uniform dosing interval τ	up to 32 days
Maximum measured concentration of BI 1358894 in plasma at steady state over a uniform dosing interval τ	up to 32 days
Area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point	up to 32 days
Maximum measured concentration of the analyte in plasma	up to 32 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2018
• Primary Completion (ACTUAL): July 22, 2019
• Study Completion (ACTUAL): July 22, 2019

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (ACTUAL): November 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 1402-0002; 2018-000389-12 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

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

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, except for the following exclusions:

1. Studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. Studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:

1. find information in order to request access to clinical study data, for listed studies.
2. request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement.

Drug and device information, study documents

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