Evaluation and Validation of Endogenous Markers for the Assessment of CYP3A Activity in Korean Healthy Subjects Using Metabolomics (CYP3A_basal)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Midazolam I.V.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Jieon Lee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance (CL) of midazolam	Pharmacokinetics of midazolam	Up to 12 hours after midazolam administration
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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: December 23, 2014
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (Estimate): October 19, 2015

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: CYP3A
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: CYP3A_basal