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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Midazolam I.V.

• Registration Number: NCT02579434
• Lead Sponsor: Seoul National University Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2014-12-23
• Primary Completion: 2015-05
• Study First Submitted QC: 2015-10-15
• Study First Posted: 2015-10-19
• Status Verified: 2016-04
• Study Completion: 2016-04
• Last Update Submitted: 2016-04-15
• Last Update Posted: 2016-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Female elderly adults	Midazolam I.V.	Arm 3: Female healthy volunteers aged over 45 years Midazolam (IV) on day 1
Female young adults	Midazolam I.V.	Arm 4: Female healthy volunteers aged 20 to 45 years Midazolam (IV) on day 1, Day 15
Male young adults	Midazolam I.V.	Arm 1: Male healthy volunteers aged from 20 to 45 years Midazolam (IV) on day 1
Male elderly adults	Midazolam I.V.	Arm 2: Male healthy volunteers aged over 45 years Midazolam (IV) on day 1

Primary Outcome Measures

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

Trial Locations

Locations (1)

Jieon Lee; 🇰🇷 Seoul, Korea, Republic of