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

NCT01760642 | Completed Phase 1 DMC

• 1 other identifier: CYP_metabolomics
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

metabolite profiles; pharmacokinetics; CYP3A; metabolomics

Outcome Measures

Primary Outcomes (1)

• Metabolomic profile

  endogenous metabolite profiles such as steroid

  -24--12h, -12-0h of every midazolam dosing

Secondary Outcomes (1)

• Pharmacokinetics

  0h, 10m, 20m, 30m, 45m, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h of every midazolam dosing

Study Arms (1)

Midazolam

EXPERIMENTAL

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; Drug: Ketoconazole; Drug: Rifampicin

Interventions

Midazolam DRUG

Midazolam 3 mg IV

Also known as: Midazolam (Bukwang Pharm.Co., Ltd.)

Midazolam

Ketoconazole DRUG

ketoconazole 400 mg PO

Also known as: Kaszole (Skynewpharm Inc.)

Midazolam

Rifampicin DRUG

Rifampicin 600 mg PO

Also known as: Rifampin (Yuhan Corp.)

Midazolam

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National Universtiy Hospital

Seoul, 110-744, South Korea

Location

Related Publications (1)

• Shin KH, Ahn LY, Choi MH, Moon JY, Lee J, Jang IJ, Yu KS, Cho JY. Urinary 6beta-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.

  PMID: 27317471 DERIVED

MeSH Terms

Interventions

Midazolam; Long-Term Synaptic Depression; Ketoconazole; Rifampin

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Neuronal Plasticity; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Piperazines; Heterocyclic Compounds, 1-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Joo-Youn Cho, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 26, 2012
• First Posted: January 4, 2013
• Study Start: December 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: May 26, 2014

Record last verified: 2014-05

Locations

KR (1)