Evaluation and Validation of Metabolic Markers for the Assessment of CYP3A Activity and Prediction of DDI (CYP3A_weak)

Evaluation and Validation of Metabolic Markers for the Assessment of CYP3A Activity and Prediction of Drug-drug Interaction in Korean Healthy Subjects

Evaluation and validation of metabolic markers for the assessment of CYP3A activity and prediction of drug-drug interaction in Korean healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: itraconazole; Drug: rifampicin

Detailed Description

Eligibility for participation of this study will be determined from demographic information, medical history, physical examination, electrocardiogram (ECG) and clinical laboratory tests within 4 weeks before study drug administration. Subjects suitable for this study will be admitted to the Clinical Trials Center, Seoul National University Hospital on the day before dosing, and they were overnight-fasted from 10 p.m. of Day -1. Urine collection is scheduled drug 12 hour before and 24 hour after midazolam administration. Subjects will be dosed study drug via intravenous around at 9 a.m. of Day 1. Subjects performed scheduled procedures.

In period 2, Subjects will be admitted on Day 3-5. Subjects performed scheduled period 2 (Itraconazole co-administration phase, 2 times administration of itraconazole 200 mg), and period 3 (rifampicin 150 mg co-administration phase) procedure. Study participation was terminated on post-study visit (Day 23~35).

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age: Between 20 to 40 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, 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 60 days prior to the participation of the study
• Judged to be inappropriate for the study by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: midazolam alone; midazolam administration alone	Drug: Midazolam; Other Names: Bukwang Midazolam, Korea
Experimental: midazolam and itraconazole; Itraconazole 200 mg PO twice; midazolam iv single administration	Drug: Midazolam; Other Names: Bukwang Midazolam, Korea; Drug: itraconazole
Experimental: midazolam and rifampicin; rifampicin 150 mg PO for 9 days administration, midazolam iv single administration	Drug: Midazolam; Other Names: Bukwang Midazolam, Korea; Drug: rifampicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitation of endogenous metabolites	endogenous metabolite profiles such as steroids to predict CYP3A activity	-12h-24h
Maximum plasma concentration and area under the cure from zero to last point	Cmax, AUClast of midazolam	Time Frame: 0h, 10m, 20m, 30m, 45m, 1h, 2h, 3h, 4h, 6h, 8h, 12h

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: December 23, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Estimate): April 19, 2016
• Last Update Submitted That Met QC Criteria: April 15, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Metabolomics; CYP3A
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Midazolam; Rifampin; Itraconazole
• Other Study ID Numbers: CYP3A_weak