A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 1358894 in the Blood

Relative Bioavailability of a Single Oral Dose of BI 1358894 When Administered Alone or in Combination With Multiple Oral Doses of Itraconazole in Healthy Male Subjects (an Open-label, Fixed Sequence Study)

The main objective of this trial is to investigate the relative bioavailability of BI 1358894 in plasma when given as oral single dose together with multiple oral doses of itraconazole (Test, T) as compared to when given alone as oral single dose (Reference, R).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13627
    • CRS Clinical Research Services Berlin GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male subjects according to the assessment of the investigator, as 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 (inclusive)
• Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
• 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 1 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 1 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)) deviating from normal and assessed 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 (CRP)> 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
• Any evidence of a concomitant disease assessed as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or 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 medications or their excipients)
• Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause 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 of planned administration of trial medication or intended blood donation during the trial
• Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
• Inability to comply with the dietary regimen of the 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 Torsade 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 the subject is not considered 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 Columbia Suicide Severity Rating Scale (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)
• Any history of drug-induced liver failure.
• History of ventricular dysfunction or congestive heart failure.
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Total of the 2-treatment, 2-period, fixed-sequence trial; Treatment period 1 (Reference (R)): Oral administration of single dose of 10 milligram (mg) BI 1358894 (2 tablets of 5 mg) with 240 milliliter (mL) of water after an high-fat, high-calorie breakfast on Day 1 of Treatment Period 1. Treatment period 2 (Test (T)): Oral administration of 200 mg itraconazole (20 mL of 10 mg/mL solution) with 240 mL of water after an overnight fast for at least 10 h once daily for 14 days on Days -3 to 11 combined with a single dose of 10 mg BI 1358894 (2 tablets of 5 mg) on Day 1 of Treatment Period 2, 1.5 hours after administration of itraconazole. Administrations of BI 1358894 were separated by a washout interval of at least 17 days.

Drug: BI 1358894; Oral administration of single dose of 10 milligram (mg) BI 1358894 (2 tablets of 5 mg) with 240 milliliter (mL) of water after an high-fat, high-calorie breakfast on Day 1 of Treatment Period 1.; Drug: Itraconazole; Oral administration of 200 mg itraconazole (20 mL of 10 mg/mL solution) with 240 mL of water after an overnight fast for at least 10 h once daily for 14 days on Days -3 to 11 combined with a single dose of 10 mg BI 1358894 (2 tablets of 5 mg) on Day 1 of Treatment Period 2, 1.5 hours after administration of itraconazole.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity	Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Data presented come from an analysis of variance (ANOVA) model on the logarithmic scale, this model included effects accounting for 'subject' and 'treatment'. The 'subject' effect was considered as random, whereas the 'treatment' effect was considered as fixed.	For each period: within 2.5 hours prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168, 192, 216, 240, 312 and 480* hours after administration of BI 1358894. *only in the second period.
Maximum Measured Concentration of BI 1358894 in Plasma	Maximum measured concentration of BI 1358894 in plasma (Cmax). Data presented come from an analysis of variance (ANOVA) model on the logarithmic scale, this model included effects accounting for 'subject' and 'treatment'. The 'subject' effect was considered as random, whereas the 'treatment' effect was considered as fixed.	For each period: within 2.5 hours prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168, 192, 216, 240, 312 and 480* hours after administration of BI 1358894. *only in the second period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point	Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 to the last quantifiable data point. Data presented come from an analysis of variance (ANOVA) model on the logarithmic scale, this model included effects accounting for 'subject' and 'treatment'. The 'subject' effect was considered as random, whereas the 'treatment' effect was considered as fixed.	For each period: within 2.5 hours prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168, 192, 216, 240, 312 and 480* hours after administration of BI 1358894. *only in the second period.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): June 3, 2019
• Study Completion (Actual): June 3, 2019

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP3A Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 1402-0007; 2018-004274-10 (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, 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).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

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