Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin - Full Text View

Sponsor:	Liuhuaqiao Hospital
Collaborator:	Guangdong Province, Department of Science and Technology
Information provided by:	Liuhuaqiao Hospital
ClinicalTrials.gov Identifier:	NCT00973986

Purpose

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.

Condition	Intervention	Phase
Coronary Heart Disease	Drug: Atorvastatin	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Study the Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin in Chinese Subjects With Coronary Heart Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Coronary Artery Disease Heart Diseases

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by Liuhuaqiao Hospital:

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. [ Time Frame: 48h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The pharmacokinetics of atorvastatin in Chinese with coronary heart disease. [ Time Frame: 48h ] [ Designated as safety issue: No ]

Enrollment:	20
Study Start Date:	June 2009
Study Completion Date:	March 2011
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: CYP3A41/1	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: CYP3A41/1G	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: CYP3A41G/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

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.

Eligibility

Ages Eligible for Study:	35 Years to 65 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00973986

Locations

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

Sponsors and Collaborators

Liuhuaqiao Hospital

Guangdong Province, Department of Science and Technology

Investigators

Study Director:

Zhao Shujin, PhD

Guangzhou General Hospital of Guangzhou Military Command

More Information

No publications provided

Responsible Party:	Department of pharmacy, Guangzhou General Hospital of Guangzhou Military Command
ClinicalTrials.gov Identifier:	NCT00973986 History of Changes
Other Study ID Numbers:	YWLCSY-0900328, 08110831, GZJQZYY-003, ATR-01, GD080625, 20081001
Study First Received:	September 4, 2009
Last Updated:	November 28, 2011
Health Authority:	China: Ethics Committee

Keywords provided by Liuhuaqiao Hospital:

atorvastatin
genetic polymorphisms
coronary heart disease
pharmacokinetics
CYP3A

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Atorvastatin

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012