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

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

Detailed Description
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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).

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Midazolam
* Drug: itraconazole
* Drug: rifampicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CYP3A, Metabolomics