Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin

Coronary Heart Disease Clinical Trial

— ECGPPA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00973986
• Other study ID #: YWLCSY-0900328
• Secondary ID: 08110831GZJQZYY-
• Status: Completed
• Phase: Phase 1
• First received: September 4, 2009
• Last updated: November 28, 2011
• Start date: June 2009
• Est. completion date: March 2011

Study information

• Verified date: September 2009
• Source: Liuhuaqiao Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 35 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

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.

Locations

Country	Name	City	State
China	Guangzhou General Hospital of Guangzhou Military Command	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Liuhuaqiao Hospital	Guangdong Province, Department of Science and Technology

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		48h	No
Secondary	The pharmacokinetics of atorvastatin in Chinese with coronary heart disease.		48h	No