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

NCT03843151 | Completed Phase 1 Results

• 2 other identifiers: 1402-00072018-004274-10
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point

  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.

Study Arms (1)

Total of the 2-treatment, 2-period, fixed-sequence trial

EXPERIMENTAL

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; Drug: Itraconazole

Interventions

BI 1358894 DRUG

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.

Total of the 2-treatment, 2-period, fixed-sequence trial

Itraconazole DRUG

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.

Total of the 2-treatment, 2-period, fixed-sequence trial

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

CRS Clinical Research Services Berlin GmbH

Berlin, 13627, Germany

Location

MeSH Terms

Interventions

TRPC inhibitor BI 1358894; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 15, 2019
• Study Start: March 19, 2019
• Primary Completion: June 3, 2019
• Study Completion: June 3, 2019
• Last Updated: February 21, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)