Clinical trial NCT00973986: Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin
Official title: Study the Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin in Chinese Subjects With Coronary Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Coronary Heart Disease
Keywords: atorvastatin
genetic polymorphisms
coronary heart disease
pharmacokinetics
CYP3A
Lead sponsor: Liuhuaqiao Hospital
Sponsor class: OTHER
Collaborators: name: Guangdong Province, Department of Science and Technology
First posted: 2009-09-09
Enrollment: 20
Sex: MALE
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: 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.
timeFrame: 48h
Secondary outcomes:
measure: The pharmacokinetics of atorvastatin in Chinese with coronary heart disease.
timeFrame: 48h
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou General Hospital of Guangzhou Military Command
state: Guangdong
Study officials:
affiliation: Guangzhou General Hospital of Guangzhou Military Command
name: Zhao Shujin, PhD
role: STUDY_DIRECTOR
References:
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.