Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin (ECGPPA)

November 28, 2011 updated by: Liuhuaqiao Hospital

Study the Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin in Chinese Subjects With Coronary Heart Disease

The aim of the study is to investigate the effects of CYP3A polymorphisms on the pharmacokinetics of Atorvastatin in Chinese subjects with coronary heart disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Large variability exists in the individual response to statins. CYP3A polymorphisms likely contribute to variable response to those drugs primarily metabolized by CYP3A including atorvastatin.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510010
        • Guangzhou General Hospital of Guangzhou Military Command

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
  • Subjects must be >=35 years and <=70 years of age.
  • Subjects must have an LDL-C concentration >=2.6 mmol/L and TC concentration >=4.14 mmol/L
  • Body mass index (BMI) must be within the range of 19 to 30 for patients.

  • Subjects must have documented coronary heart disease with one or more of the following features:

    • Documented stable angina (with evidence of ischemia on exercise testing)
    • History of myocardial infarction
    • History of percutaneous coronary intervention (with or without stent placement)
    • Documented history of unstable angina or non-Q wave myocardial infarction.

Exclusion Criteria:

  • Diabetes and endocrine or metabolic disease.
  • Congestive heart failure defined by New York Heart Association (NYHA) as Class III or IV.
  • Uncontrolled cardiac arrhythmia.
  • Uncontrolled hypertension (Systolic BP >160 mm Hg and/or Diastolic BP >100 mmHg on two consecutive measurements).
  • Liver or kidney disease confirmed by abnormal lab values or function.
  • Smokers who report cigarette use of more then 10 cigarette per day.
  • Subjects who consume >2 alcoholic drinks a day. (A drink is: a can of beer, glass of wine, or single measure of spirits).
  • Known human immunodeficiency virus (HIV) positive.
  • Cancer.

  • Subjects who are on any of the following concomitant medications:

    • Medications that are potent inhibitors of CYP3A, including cyclosporine, itraconazole, fluconazole, and ketoconazole, erythromycin or clarithromycin, nefazodone, protease inhibitors,mibefradil and large amounts of grapefruit juice (>1 quart/day).
    • Lipid-lowering agent: niacin (>200 mg/day) taken within 5 weeks, fibric acid derivatives taken within 8 weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CYP3A4*1/*1
Drug: Atorvastatin
The subjects will receive atorvastatin (20 mg single dose) orally with approximately 240 ml of water. Blood samples(4 mL) will be taken prior to dosing and at 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24 and 48 h after drug administration.
Other Names:
  • Lipitor
  • Atorvastatin Calcium Tablets
Active Comparator: CYP3A4*1/*1G
Drug: Atorvastatin
The subjects will receive atorvastatin (20 mg single dose) orally with approximately 240 ml of water. Blood samples(4 mL) will be taken prior to dosing and at 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24 and 48 h after drug administration.
Other Names:
  • Lipitor
  • Atorvastatin Calcium Tablets
Active Comparator: CYP3A4*1G/*1G
Drug: Atorvastatin
The subjects will receive atorvastatin (20 mg single dose) orally with approximately 240 ml of water. Blood samples(4 mL) will be taken prior to dosing and at 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24 and 48 h after drug administration.
Other Names:
  • Lipitor
  • Atorvastatin Calcium Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Compare the area under the plasma concentration versus time curve (AUC) and Area under the plasma concentration versus time curve (AUC) of atorvastatin with different CYP3A4*1G genotypes.
Time Frame: 48h
48h

Secondary Outcome Measures

Outcome Measure
Time Frame
The pharmacokinetics of atorvastatin in Chinese with coronary heart disease.
Time Frame: 48h
48h

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liuhuaqiao Hospital

Collaborators

Guangdong Province, Department of Science and Technology

Investigators

  • Study Director: Zhao Shujin, PhD, Guangzhou General Hospital of Guangzhou Military Command

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

September 4, 2009

First Submitted That Met QC Criteria

September 8, 2009

First Posted (Estimate)

September 9, 2009

Study Record Updates

Last Update Posted (Estimate)

November 29, 2011

Last Update Submitted That Met QC Criteria

November 28, 2011

Last Verified

September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • YWLCSY-0900328
  • 08110831
  • GZJQZYY-003
  • ATR-01
  • GD080625
  • 20081001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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