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

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ClinicalTrials.gov Identifier: NCT01760642
Recruitment Status : Completed
First Posted : January 4, 2013
Last Update Posted : May 26, 2014
Sponsor:
Information provided by (Responsible Party):
Joo-Youn Cho, Seoul National University Hospital

Tracking Information
First Submitted Date  ICMJE December 26, 2012
First Posted Date  ICMJE January 4, 2013
Last Update Posted Date May 26, 2014
Study Start Date  ICMJE December 2012
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 1, 2013)
Metabolomic profile [ Time Frame: -24--12h, -12-0h of every midazolam dosing ]
endogenous metabolite profiles such as steroid
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 1, 2013)
Pharmacokinetics [ Time Frame: 0h, 10m, 20m, 30m, 45m, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h of every midazolam dosing ]
Cmax, AUClast of midazolam
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Identification and Evaluation of Endogenous Markers for the Assessment of CYP3A Activity
Official Title  ICMJE Identification and Evaluation of Endogenous Markers for the Assessment of CYP3A Activity in Female Subjects Using Metabolomics
Brief Summary Identification and evaluation of endogenous markers for the assessment of CYP3A activity in female subjects using metabolomics
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • 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.)
Study Arms  ICMJE 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.

Interventions:
  • Drug: Midazolam
  • Drug: Ketoconazole
  • Drug: Rifampicin
Publications * Shin KH, Ahn LY, Choi MH, Moon JY, Lee J, Jang IJ, Yu KS, Cho JY. Urinary 6β-Hydroxycortisol/Cortisol Ratio Most Highly Correlates With Midazolam Clearance Under Hepatic CYP3A Inhibition and Induction in Females: A Pharmacometabolomics Approach. AAPS J. 2016 Sep;18(5):1254-1261. doi: 10.1208/s12248-016-9941-y. Epub 2016 Jun 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 1, 2013)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 20 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01760642
Other Study ID Numbers  ICMJE CYP_metabolomics
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joo-Youn Cho, Seoul National University Hospital
Study Sponsor  ICMJE Seoul National University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joo-Youn Cho, PhD Seoul National University Hospital
PRS Account Seoul National University Hospital
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP