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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: BI 1323495
Drug: Itraconazole

Registration Number: NCT04011241

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 14

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Reference - BI 1323495 alone	BI 1323495	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.
Test - BI 1323495 + Itraconazole	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.
Test - BI 1323495 + Itraconazole	BI 1323495	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.

Primary Outcome Measures

Name	Time	Method
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.	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)
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.	Maximum measured concentration of BI 1323495 in plasma (Cmax)

Secondary Outcome Measures

Name	Time	Method
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.	Area under the concentration-time cure of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)