Evaluation and Validation of Endogenous Markers for the Assessment of CYP3A Activity in Korean Healthy Subjects Using Metabolomics

NCT02579434 | Completed Phase 1

• 1 other identifier: CYP3A_basal
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The study objective is to evaluate and validate of endogenous markers for the assessment of CYP3A activity in Korean healthy subjects using metabolomics. In part 1, total 75 healthy subjects (males and females) will be enrolled. In part 2, total 25 healthy female subject aged 20-45 years will be enrolled. In both part A and B, subjects will be administered midazolam I.V. 1 mg.

Conditions

Healthy Volunteers

Keywords

CYP3A

Outcome Measures

Primary Outcomes (3)

• Area under the curve of midazolam (AUC12h)

  Pharmacokinetics of midazolam

  Up to 12 hours after midazolam administration

• Metabolic ratio of steroids

  endogenous metabolite profiles such as steroid (6beta-hydroxy-cortisol/cortisol, 6beta-hydroxy-cortisone/cortisone)

  12h-12h

• Clearance (CL) of midazolam

  Pharmacokinetics of midazolam

  Up to 12 hours after midazolam administration

Study Arms (4)

Male young adults

EXPERIMENTAL

Arm 1: Male healthy volunteers aged from 20 to 45 years Midazolam (IV) on day 1

Drug: Midazolam I.V.

Male elderly adults

EXPERIMENTAL

Arm 2: Male healthy volunteers aged over 45 years Midazolam (IV) on day 1

Drug: Midazolam I.V.

Female elderly adults

EXPERIMENTAL

Arm 3: Female healthy volunteers aged over 45 years Midazolam (IV) on day 1

Drug: Midazolam I.V.

Female young adults

EXPERIMENTAL

Arm 4: Female healthy volunteers aged 20 to 45 years Midazolam (IV) on day 1, Day 15

Drug: Midazolam I.V.

Interventions

Midazolam I.V. DRUG

Midazolam I.V. 1mg/ml

Female elderly adults; Female young adults; Male elderly adults; Male young adults

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Between 20 to 80 years of age, inclusive
• Weight: Between 45 to 95 kg, within 17 - 28 of Body Mass Index
• 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 abnormal A subject whose systolic blood pressure is over 140 mmHg or below 90 mmHg and diastolic blood pressure 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
• 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)

Jieon Lee

Seoul, South Korea

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 23, 2014
• First Posted: October 19, 2015
• Study Start: December 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: April 1, 2016
• Last Updated: April 19, 2016

Record last verified: 2016-04

Locations

KR (1)