Evaluation of Metabolic Markers for the Prediction of DDI of Various CYP3A Substrates and Inhibitors

NCT ID: NCT02975037

Last Updated: 2022-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-06
• Study Completion Date: 2017-06-23

Brief Summary

Evaluation and validation of metabolic markers for the prediction of drug-drug interaction of various CYP3A4 substrates (sildenafil) and inhibitors (erythromycin/itraconazole) in healthy male subjects

Detailed Description

Subjects suitable for this study will be admitted to the Clinical Trials Center, Seoul National University Hospital on the day before dosing, and they will be overnight-fasted from 9P of Day -1. Urine collection is scheduled from 12 hours before sildenafil administration to 12 hours after administration. Subjects will be administered sildenafil (oral) around at 9A of Day 1. Subjects will perform scheduled procedures including clinical laboratory tests, electrocardiograms and blood samplings for pharmacokinetic, pharmacometabolomic and mRNA assessment.

Subjects will be administered either erythromycin or itraconazole (oral) around at 9A on Day 3 and 9A/9P on Day 4. Urine collection is scheduled from 0 hour to 12 hours after Day 3 erythromycin or itraconazole administration. Subjects will perform scheduled procedures including clinical laboratory tests, electrocardiograms and blood samplings for pharmacokinetic, pharmacometabolomic and mRNA assessment.

On Day 5, sildenafil will be administered with erythromycin or itraconazole around at 9A. Urine collection is scheduled from 12 hours before Day 5 drug administration to 12 hours after administration. Subjects will perform scheduled procedures. After subjects perform scheduled procedure, the study will be discharged (around 9A of Day 6).

Study participation was terminated on post-study visit (Day 12-14).

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

sildenafil+clarithromycin

Sildenafil 25 mg PO (single dose); Clarithromycin 250 mg PO (3 doses); Sildenafil 25 mg PO + Clarithromycin 250 mg PO (single dose)

Group Type: EXPERIMENTAL

Sildenafil

Intervention Type: DRUG

sildenafil 25 mg PO

Clarithromycin

Intervention Type: DRUG

clarithromycin 250 mg PO

sildenafil+itraconazole

Sildenafil 25 mg PO (single dose); Itraconazole 100 mg PO (3 doses); Sildenafil 25 mg PO + Itraconazole 100 mg PO (single dose)

Group Type: EXPERIMENTAL

Sildenafil

Intervention Type: DRUG

sildenafil 25 mg PO

Itraconazole

Intervention Type: DRUG

itraconazole 100 mg PO

Interventions

Sildenafil

sildenafil 25 mg PO

Intervention Type: DRUG

Clarithromycin

clarithromycin 250 mg PO

Intervention Type: DRUG

Itraconazole

itraconazole 100 mg PO

Intervention Type: DRUG

Other Intervention Names

VIAGRA TAB, Pfizer Pharmaceuticals Korea Limited, Korea; CLARI TAB, Hanmi Pharm.Co.,Ltd., Korea; ITRA TAB, Hanmi Pharm.Co.,Ltd., Korea

Eligibility Criteria

Inclusion Criteria

• Age: Between 19 to 50 years of age, inclusive
• Weight: within 17-28 of Body Mass Index (BMI)
• Subject who are reliable and willing to make themselves available during the study period.
• Subject who are willing to follow the study protocol, and give their written informed consent voluntarily.

Exclusion Criteria

• History of hypersensitive reaction to medication (midazolam, itraconazole, rifampicin)
• History of significant clinical illness needs medical caution, including cardiovascular, immunologic, hematologic, neuropsychiatric, respiratory, gastrointestinal, hepatic, or renal disease or other chronic disease
• History or evidence of drug abuse
• Use any prescriptive medication, Korean traditional medication not considered acceptable by the clinical investigator during the last 14 days period before first dosing, or use any medication not considered acceptable by the clinical investigator during the last 7 days period before first dosing (if used medication is considered acceptable by investigator, patients can be included)
• Participation in clinical trials of any drug within 3 months prior to the participation of the study
• Judged to be inappropriate for the study by the investigator

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Joo-Youn Cho

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joo-Youn Cho

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

Seoul National University Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

CYP3A_DDI

Identifier Type: -

Identifier Source: org_study_id