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

This study is currently recruiting participants.
Verified January 2013 by Seoul National University Hospital
Sponsor:
Information provided by (Responsible Party):
Joo-Youn Cho, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01760642
First received: December 26, 2012
Last updated: January 1, 2013
Last verified: January 2013
  Purpose

Identification and evaluation of endogenous markers for the assessment of CYP3A activity in female subjects using metabolomics


Condition Intervention Phase
Healthy
Drug: Midazolam
Drug: Ketoconazole
Drug: Rifampicin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Identification and Evaluation of Endogenous Markers for the Assessment of CYP3A Activity in Female Subjects Using Metabolomics

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Metabolomic profile [ Time Frame: -24--12h, -12-0h of every midazolam dosing ] [ Designated as safety issue: Yes ]
    endogenous metabolite profiles such as steroid


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 0h, 10m, 20m, 30m, 45m, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h of every midazolam dosing ] [ Designated as safety issue: Yes ]
    Cmax, AUClast of midazolam


Estimated Enrollment: 16
Study Start Date: December 2012
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Midazolam

period 1: midazolam 1 mg IV single dose administration. period 2: midazolam 1 mg IV single dose after ketoconazole 400 mg oral dosing for 3 days.

period 3: midazolam 2.5 mg IV single dose after rifampicin 600 mg oral dosing for 10 days.

Drug: Midazolam
Midazolam 3 mg IV
Other Name: Midazolam (Bukwang Pharm.Co., Ltd.)
Drug: Ketoconazole
ketoconazole 400 mg PO
Other Name: Kaszole (Skynewpharm Inc.)
Drug: Rifampicin
Rifampicin 600 mg PO
Other Name: Rifampin (Yuhan Corp.)

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 will be overnight-fasted from 9 p.m. of Day -1. Urine collection is scheduled from 24 hours before midazolam administration to 24 hours after administration. Subjects will be dosed midazolam by intravenous around at 9 a.m. of Day 1. Subjects will perform scheduled procedures including clinical laboratory tests, electrocardiograms and pharmacokinetic samplings. Subjects will be discharged on Day 2 and visit the Clinical Trials Center for period 2, ketoconazole administration. After 3 days of ketoconazole administration, midazolam will be dosed with ketoconazole on Day 4 of period 2. Subjects will perform scheduled procedure and on period 3 rifampicin will be dosed for 9 days and on Day 10 of period 3 midazolam will be dosed with rifampicin. After subjects perform scheduled procedure, the study will be terminated 6-8 days after the end of period 3.

  Eligibility

Ages Eligible for Study:   20 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age: Between 20 to 50 years of age, inclusive
  • Weight: Between 45 to 95 kg, within 17 - 28 of Body Mass Index
  • Menstruation cycle between 21 to 35 without contraceptive
  • 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 as follows; Liver function test (AST, ALT, GGT, ALP, LDH, Total bilirubin) > 1.25 X upper limit of reference range
  • A subject whose SBP is over 140 mmHg or below 90 mmHg and DBP 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, 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)
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01760642

Contacts
Contact: Li Young Ahn 82-2-2072-1666 helloahn@snu.ac.kr

Locations
Korea, Republic of
Seoul National Universtiy Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Li Young Ahn       helloahn@snu.ac.kr   
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Joo-Youn Cho, PhD Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Joo-Youn Cho, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01760642     History of Changes
Other Study ID Numbers: CYP_metabolomics
Study First Received: December 26, 2012
Last Updated: January 1, 2013
Health Authority: Korea: Institutional Review Board

Keywords provided by Seoul National University Hospital:
metabolite profiles
pharmacokinetics
CYP3A
metabolomics

Additional relevant MeSH terms:
Midazolam
Ketoconazole
Rifampin
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014