Identification and Evaluation of Endogenous Markers for the Assessment of CYP3A Activity Using Metabolomics

Identification and evaluation of endogenous markers for the assessment of CYP3A activity using metabolomics.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: midazolam

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 3 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 24 hour before midazolam administration. Subjects will be dosed study drug via intravenous around at 9 a.m. of Day 1. Subjects performed scheduled procedures including clinical laboratory tests, electrocardiograms and pharmacokinetic samplings. Subjects will be discharged on Day 2, and visited Clinical Trials Center on Day 5-7 for ketoconazole administration. Subjects will be admitted on Day 7 for period 2. Subjects performed scheduled period 2 (ketoconazole co-administration phase), and period 3 (rifampicin co-administration phase) procedure. Study participation was terminated on post-study visit (Day 30-32).

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

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age: Between 20 to 50 years of age, inclusive
• Weight: Between 50 - 95 kg, within 17-28 of Body Mass Index
• 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
• 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 OTC 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: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: midazolam; period 1: midazolam administration alone period 2: ketoconazole 400 mg PO for 4 days administration, midazolam iv single administration period 3: rifampicin 600 mg PO for 9 days administration, midazolam iv single administration	Drug: midazolam; midazolam: 3mg iv; Other Names: Bukwang midazolam, Korea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomic profile	endogenous metabolite profiles such as steroids	-24- -12h, -12- 0h of every midazolam dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Cmax, AUClast of midazolam	0h, 10m, 20m, 30m, 45m, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Ministry of Education Science and Technology, Korea
• Investigators: Principal Investigator: Joo-Youn Cho, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: October 4, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimate): October 6, 2010

Study Record Updates

• Last Update Posted (Estimate): February 23, 2011
• Last Update Submitted That Met QC Criteria: February 19, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: pharmacokinetics; metabolomics; CYP3A; metabolite profiles
• 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: SNUCPT10_CYP3A