Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joo-Youn Cho, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01760642
First received: December 26, 2012
Last updated: May 23, 2014
Last verified: May 2014
  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


Enrollment: 16
Study Start Date: December 2012
Study Completion Date: September 2013
Primary Completion Date: September 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01760642

Locations
Korea, Republic of
Seoul National Universtiy Hospital
Seoul, Korea, Republic of, 110-744
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: May 23, 2014
Health Authority: Korea: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on November 24, 2014