A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 1323495 in the Blood

Relative Bioavailability of a Single Oral Dose of BI 1323495 When Administered Alone or in Combination With Multiple Oral Doses of Itraconazole in Healthy Male Subjects (an Open-label, One-way Crossover Study)

The main objective of this trial is to investigate the relative bioavailability of BI 1323495 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 1323495; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 14
• 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 50 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 50 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
• further inclusion criteria apply

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 45 to 90 bpm
• Any 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, blood coagulation, 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 medication or its 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)
• Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
• 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 24 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) 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
• Current or history of relevant kidney, urinary tract diseases or abnormalities (e.g. nephrolithiasis, hydronephrosis, acute or chronic nephritis, renal injury, renal failure)
• Estimated glomerular filtration rate according to CKD-EPI formula < 90 mL/min at screening
• 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)
• History of drug induced liver injury
• Liver enzymes (ALT, AST, GGT) above upper limit of normal at the screening examination
• History of heart failure, or any evidence of ventricular dysfunction
• Known sorbitol/polyols intolerance
• Subjects with female partner of childbearing potential who are unwilling to use male contraception (condom or sexual abstinence) from first administration until 30 days after last administration of trial medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reference - BI 1323495 alone; Single oral dose of 10 milligrams (mg) of film-coated tablet of BI 1323495 was administered once on day 1 in the first treatment period (period 1, visit 2) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) as reference treatment R.	Drug: BI 1323495; Tablet
Experimental: Test - BI 1323495 + Itraconazole; Single oral dose of 200 mg itraconazole (oral solution, 20 milliliter (mL) per day with 10 mg/mL) was administered once daily with 240 mL of water after an overnight fast of 9 hours (h) from day -3 to day 7 (total: 10 doses) in the second treatment period (period 2, visit 3) together with a single oral dose of 10 mg BI 1323495 administered 1 h after itraconazole administration with 240 mL of water after an overnight fast of 10 h on the fourth day of the itraconazole treatment (day 1, period 2, visit 3) as test treatment T.	Drug: BI 1323495; Tablet; Drug: Itraconazole; Oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)	Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration.
Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)	Maximum measured concentration of BI 1323495 in plasma (Cmax)	Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Cure of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time cure of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)	Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2019
• Primary Completion (Actual): September 6, 2019
• Study Completion (Actual): September 6, 2019

Study Registration Dates

• First Submitted: July 5, 2019
• First Submitted That Met QC Criteria: July 5, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 1405-0009; 2019-001570-28 (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: http://trials.boehringer-ingelheim.com/

Drug and device information, study documents

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