Evaluation and Validation of Endogenous Markers for the Assessment of CYP3A Activity in Korean Healthy Subjects Using Metabolomics

Study Overview
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Brief Summary
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The study objective is to evaluate and validate of endogenous markers for the assessment of CYP3A activity in Korean healthy subjects using metabolomics. In part 1, total 75 healthy subjects (males and females) will be enrolled. In part 2, total 25 healthy female subject aged 20-45 years will be enrolled. In both part A and B, subjects will be administered midazolam I.V. 1 mg.

Official Title
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Evaluation and Validation of Endogenous Markers for the Assessment of CYP3A Activity in Korean Healthy Subjects Using Metabolomics

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Midazolam I.V.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: Between 20 to 80 years of age, inclusive Weight: Between 45 to 95 kg, within 17 - 28 of Body Mass Index Subject who agree contraception during the study 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, ketoconazole, 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 A subject whose lab test results are abnormal A subject whose systolic blood pressure is over 140 mmHg or below 90 mmHg and diastolic blood pressure is over 100 mmHg or below 50 mmHg Presence or history of drug abuse or positive result in urine drug screening test Blood donation during 2 months or apheresis during 1 month before the study Use any prescriptive medication Use of alcohol over 21 units/weeks Smoker who smoke more than 10 cigarettes per day Participation in clinical trials of any drug within 60 days prior to the participation of the study Use of grapefruit juice within 1 week before first dose Use of caffeine drink within 3 days before first dose Subject pregnant or breast-feeding Judged to be inappropriate for the study by the investigator

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Male young adults<br>Arm 1: Male healthy volunteers aged from 20 to 45 years Midazolam (IV) on day 1 | Drug: Midazolam I.V.<br>* Midazolam I.V. 1mg/ml<br>|
| Experimental: Male elderly adults<br>Arm 2: Male healthy volunteers aged over 45 years Midazolam (IV) on day 1 | Drug: Midazolam I.V.<br>* Midazolam I.V. 1mg/ml<br>|
| Experimental: Female elderly adults<br>Arm 3: Female healthy volunteers aged over 45 years Midazolam (IV) on day 1 | Drug: Midazolam I.V.<br>* Midazolam I.V. 1mg/ml<br>|
| Experimental: Female young adults<br>Arm 4: Female healthy volunteers aged 20 to 45 years Midazolam (IV) on day 1, Day 15 | Drug: Midazolam I.V.<br>* Midazolam I.V. 1mg/ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of midazolam (AUC12h) | Pharmacokinetics of midazolam | Up to 12 hours after midazolam administration | 
| Metabolic ratio of steroids | endogenous metabolite profiles such as steroid (6beta-hydroxy-cortisol/cortisol, 6beta-hydroxy-cortisone/cortisone) | 12h-12h | 
| Clearance (CL) of midazolam | Pharmacokinetics of midazolam | Up to 12 hours after midazolam administration | 

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