Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin

NCT00973986 | Completed Phase 1 DMC

• 6 other identifiers: YWLCSY-090032808110831GZJQZYY-003ATR-01GD08062520081001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Heart Disease

Keywords

atorvastatin; genetic polymorphisms; coronary heart disease; pharmacokinetics; CYP3A

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• The pharmacokinetics of atorvastatin in Chinese with coronary heart disease.

  48h

Study Arms (3)

CYP3A4*1/*1

ACTIVE COMPARATOR

Drug: Atorvastatin

CYP3A4*1/*1G

ACTIVE COMPARATOR

Drug: Atorvastatin

CYP3A4*1G/*1G

ACTIVE COMPARATOR

Drug: Atorvastatin

Interventions

Atorvastatin DRUG

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.

Also known as: Lipitor, Atorvastatin Calcium Tablets

CYP3A4*1/*1; CYP3A4*1/*1G; CYP3A4*1G/*1G

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Liuhuaqiao Hospital: lead
• Guangdong Province, Department of Science and Technology: collaborator

Study Sites (1)

Guangzhou General Hospital of Guangzhou Military Command

Guangzhou, Guangdong, 510010, China

Location

Related Publications (1)

• 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.

  PMID: 24214373 DERIVED

MeSH Terms

Conditions

Coronary Disease

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Zhao Shujin, PhD

  Guangzhou General Hospital of Guangzhou Military Command

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 4, 2009
• First Posted: September 9, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: March 1, 2011
• Last Updated: November 29, 2011

Record last verified: 2009-09

Locations

CN (1)