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

Open-label, Randomised, Two-way Crossover Study to Assess the Effect of Once Daily Itraconazole on the Pharmacokinetics of BI 409306 After a Single Oral Dose in Healthy Male Volunteers Genotyped as Poor and Extensive Metabolizers of CYP2C19

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 409306; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • 1289.23.8201 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: BI 409306; Oral single dose of BI 409306; Drug: Itraconazole; Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole
Experimental: 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.	Drug: BI 409306; Oral single dose of BI 409306; Drug: Itraconazole; Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole
Experimental: 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).	Drug: BI 409306; Oral single dose of BI 409306; Drug: Itraconazole; Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole
Experimental: 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).	Drug: BI 409306; Oral single dose of BI 409306; Drug: Itraconazole; Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-infinity of BI 409306 and Its Metabolites	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) of BI 409306 and its metabolites CD 13896 and CD 14084	1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
Cmax of BI 409306 and Its Metabolites	Maximum measured concentration of the analyte in plasma (Cmax) of BI 409306 and its metabolites CD 13896 and CD 14084	1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-tz of BI 409306 and Its Metabolites	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable plasma concentration (AUC0-tz) of BI 409306 and its metabolites CD 13896 and CD 14084	1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
Tmax of BI 409306 and Its Metabolites	Time from dosing to the maximum concentration of the analyte in plasma (tmax) of BI 409306 and its metabolites CD 13896 and CD 14084	1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration
t1/2 of BI 409306 and Its Metabolites	Terminal half-life of the analyte in plasma (t1/2) of BI 409306 and its metabolites CD 13896 and CD 14084	1 hour (h) before drug administration and 10minutes (min), 20min, 30min, 45min, 1h, 1h 30min, 2h, 3h, 4h, 7h, 10h, 12h, 14h, 24h, 48h and 72h (only for test treatment) after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2014
• Primary Completion (Actual): January 7, 2015
• Study Completion (Actual): January 8, 2015

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 22, 2014
• First Posted (Estimated): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

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; Phosphodiesterase Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; BI 409306
• Other Study ID Numbers: 1289.23

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. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

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