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

Primary Purpose

Coronary Heart Disease

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Atorvastatin
Sponsored by
Liuhuaqiao Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Coronary Heart Disease focused on measuring atorvastatin, genetic polymorphisms, coronary heart disease, pharmacokinetics, CYP3A

Eligibility Criteria

35 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Guangzhou General Hospital of Guangzhou Military Command

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

CYP3A4*1/*1

CYP3A4*1/*1G

CYP3A4*1G/*1G

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

The pharmacokinetics of atorvastatin in Chinese with coronary heart disease.

Full Information

First Posted
September 4, 2009
Last Updated
November 28, 2011
Sponsor
Liuhuaqiao Hospital
Collaborators
Guangdong Province, Department of Science and Technology
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1. Study Identification

Unique Protocol Identification Number
NCT00973986
Brief Title
Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin
Acronym
ECGPPA
Official Title
Study the Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin in Chinese Subjects With Coronary Heart Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Liuhuaqiao Hospital
Collaborators
Guangdong Province, Department of Science and Technology

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Heart Disease
Keywords
atorvastatin, genetic polymorphisms, coronary heart disease, pharmacokinetics, CYP3A

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CYP3A4*1/*1
Arm Type
Active Comparator
Arm Title
CYP3A4*1/*1G
Arm Type
Active Comparator
Arm Title
CYP3A4*1G/*1G
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Other Intervention Name(s)
Lipitor, Atorvastatin Calcium Tablets
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
The pharmacokinetics of atorvastatin in Chinese with coronary heart disease.
Time Frame
48h

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhao Shujin, PhD
Organizational Affiliation
Guangzhou General Hospital of Guangzhou Military Command
Official's Role
Study Director
Facility Information:
Facility Name
Guangzhou General Hospital of Guangzhou Military Command
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510010
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
24214373
Citation
He BX, Shi L, Qiu J, Zeng XH, Zhao SJ. The effect of CYP3A4*1G allele on the pharmacokinetics of atorvastatin in Chinese Han patients with coronary heart disease. J Clin Pharmacol. 2014 Apr;54(4):462-7. doi: 10.1002/jcph.229. Epub 2013 Nov 27.
Results Reference
derived

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Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin

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