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

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ClinicalTrials.gov Identifier: NCT00973986
Recruitment Status : Completed
First Posted : September 9, 2009
Last Update Posted : November 29, 2011
Sponsor:
Collaborator:
Guangdong Province, Department of Science and Technology
Information provided by:
Liuhuaqiao Hospital

Tracking Information
First Submitted Date  ICMJE September 4, 2009
First Posted Date  ICMJE September 9, 2009
Last Update Posted Date November 29, 2011
Study Start Date  ICMJE June 2009
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2011)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 8, 2009)
CYP3A genetic polymorphisms have a dominant role in atorvastatin pharmacokinetics in vivo and CYP3A4*1G polymorphism affects the CYP3A4 enzyme. [ Time Frame: one year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2011)
The pharmacokinetics of atorvastatin in Chinese with coronary heart disease. [ Time Frame: 48h ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2009)
The pharmacokinetics of atorvastatin in Chinese with coronary heart disease. [ Time Frame: one year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin
Official Title  ICMJE Study the Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin in Chinese Subjects With Coronary Heart Disease
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Coronary Heart Disease
Intervention  ICMJE 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
Study Arms  ICMJE
  • Active Comparator: CYP3A4*1/*1
    Intervention: Drug: Atorvastatin
  • Active Comparator: CYP3A4*1/*1G
    Intervention: Drug: Atorvastatin
  • Active Comparator: CYP3A4*1G/*1G
    Intervention: Drug: Atorvastatin
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 28, 2011)
20
Original Estimated Enrollment  ICMJE
 (submitted: September 8, 2009)
36
Actual Study Completion Date  ICMJE March 2011
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 35 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00973986
Other Study ID Numbers  ICMJE YWLCSY-0900328
08110831
GZJQZYY-003
ATR-01
GD080625
20081001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Department of pharmacy, Guangzhou General Hospital of Guangzhou Military Command
Study Sponsor  ICMJE Liuhuaqiao Hospital
Collaborators  ICMJE Guangdong Province, Department of Science and Technology
Investigators  ICMJE
Study Director: Zhao Shujin, PhD Guangzhou General Hospital of Guangzhou Military Command
PRS Account Liuhuaqiao Hospital
Verification Date September 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP