Drug Drug Interaction Trial With Strong CYP3A4 Inhibitor (Itraconazole) in CYP2C19 Extensive Metabolizers and Poor Metabolizers

NCT ID: NCT02248259

Last Updated: 2024-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-08
• Study Completion Date: 2015-01-08

Brief Summary

The objective of the current study is to evaluate the effect of once daily itraconazole on the pharmacokinetics of BI 409306 in poor (PM) and extensive metabolisers (EM) of CYP2C19.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Extensive Metabolisers: Ref / Test

Participants who were extensive metabolisers received two treatments in a randomised order, the treatments were:

• Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1).
• Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1.

Group Type: EXPERIMENTAL

BI 409306

Intervention Type: DRUG

Oral single dose of BI 409306

Itraconazole

Intervention Type: DRUG

Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole

Poor Metabolisers: Ref / Test

Participants who were poor metabolisers received two treatments in a randomised order, the treatments were:

• Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1).
• Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1.

Group Type: EXPERIMENTAL

BI 409306

Intervention Type: DRUG

Oral single dose of BI 409306

Itraconazole

Intervention Type: DRUG

Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole

Extensive Metabolisers: Test / Ref

Participants who were extensive metabolisers received two treatments in a randomised order, the treatments were:

• Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1.
• Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1).

Group Type: EXPERIMENTAL

BI 409306

Intervention Type: DRUG

Oral single dose of BI 409306

Itraconazole

Intervention Type: DRUG

Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole

Poor Metabolisers: Test / Ref

Participants who were poor metabolisers received two treatments in a randomised order, the treatments were:

• Test treatment (2 capsules of 100 mg itraconazole taken orally twice daily on day -3 (loading dose) and once daily on day -2 to day 2, plus 1 tablet of 25 mg BI 409306 taken orally as a single dose 1 hour after the itraconazole administration on day 1.
• Reference (ref) treatment (1 single tablet of 25 mg BI 409306 taken orally on day 1).

Group Type: EXPERIMENTAL

BI 409306

Intervention Type: DRUG

Oral single dose of BI 409306

Itraconazole

Intervention Type: DRUG

Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole

Interventions

BI 409306

Oral single dose of BI 409306

Intervention Type: DRUG

Itraconazole

Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy CYP2C19 genotyped male volunteers according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR, respiratory rate, body temperature), 12-lead ECG, ophthalmologic exam, clinical laboratory tests

• Korean ethnicity according to the following criteria: be a current Korean passport or national identification card holder, and have parents and grandparents who were all born in Korea
• Age 20 or older than 20 and 45 or younger than 45 years
• BMI (Body Mass Index) 18.5 or more than 18.5 and BMI 25 or less than 25 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

Exclusion Criteria

• Any finding of the medical examination (including BP, PR, respiratory rate, body temperature and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract (except appendectomy, hernia surgery)
• Diseases of the central nervous system (including but not limited to any kind of seizures, migraine, stroke or psychiatric disorders) within the past 6 month
• History of relevant orthostatic hypotension, fainting spells or blackouts.
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (longer than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 20 g/day)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval more than 450 ms)
• A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Abnormality on color vision test or any other finding on ophthalmologic exam that is clinically deemed to potentially interfere with the safety assessment of this trial
• Subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until two month after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least two month)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1289.23.8201 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

Countries

South Korea

Other Identifiers

1289.23

Identifier Type: -

Identifier Source: org_study_id