Pharmacokinetic Interactions Between Amlodipine Besylate/Valsartan and Atorvastatin in Healthy Male Subjects

Study Overview
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Brief Summary
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The purpose of the study is to assess the pharmacokinetic interactions between amlodipine besylate/valsartan and atorvastatin single or co-administered in healthy volunteers.

Official Title
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An Open-label, Multiple-dosing, Two-arms, One-sequence Study to Evaluate the Safety and Pharmacokinetics After Co-administration of Exforge® (Amlodipine Besylate/Valsartan) and Lipitor® (Atorvastatin Ca) in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: combination administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male volunteers in the age between 20 and 45 years old The weight is over 55kg and is not exceed ±20% of ideal weight Ideal weight = [height -100]*0.9 Subjects with no history of any significant chronic disease Judged to be in good health on the basis of routine laboratory data obtained prior to study drug administration Willing to adhere to protocol requirements and sign a informed consent form Exclusion Criteria: Subjects with Symptoms of acute disease within 28days prior to study medication dosing Subjects with a history of gastrointestinal diseases which might significantly change ADME of medicines Subjects with a history of clinically significant allergies including drug allergies or anaphylaxis to amlodipine, valsartan and/or atorvastatin Subjects with a history of myopathy Subjects with a hereditary problems, for example, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Subject with the mean blood pressure of siDBP ≥ 150 mmHg or ≤ 90 mmHg and/or siSBP ≥ 95 mmHg or ≤ 50 mmHg at the screening visit Subjects with abnormal HDL-cholesterol(<35mg/dL) Subjects with abnormal of serum potassium concentration (<3.4 mEq/L of >5.5 mEq/L in screening visit) Subjects with a history of drug abuse Subjects taking inducer or inhibitor of drug metabolism enzyme such as barbital within 28days prior to study medication dosing Subjects who have received any drugs that might confound the results of the trial based on medical judgement by investigators within 14days prior to drug administration and OTC or vitamin within 7days prior to drug administration Participated in a previous clinical trial within 60 days prior to dosing Donated blood within 60 days prior to dosing Subjects with a history of alcohol abuse(over 21 units/week, 1 unit = 10 g of pure alcohol) or is difficult to stop drinking within study Subjects have ever smoked over 10 cigarette per day within 3 months prior to drug administration Subjects with a history of caffeine abuse or or is difficult to stop drinking within study Subjects with biliary obstruction Subjects with hepatic dysfunction (AST or ALT >3 times to accepted normal range) Subjects with moderate renal dysfunction (creatinine clearance (CLcr) < 30mL/min) Subjects considered as unsuitable based on medical judgement by investigators

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>single administration : amlodipine/valsartan 10/160mg, qd, 10days(oral) | Drug: combination administration<br>* combination administration : amlodipine/valsartan 10/160mg and atorvastatin 40mg, qd, 10days(oral)<br>|
| Experimental: Group B<br>single administration : atorvastatin 40mg, qd, 7days(oral) | Drug: combination administration<br>* combination administration : amlodipine/valsartan 10/160mg and atorvastatin 40mg, qd, 10days(oral)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate PK interaction of amlodipine and valsartan | AUCss,τ, Css,max | from pre dosing to 24hr post dose | 
| To Evaluate PK interaction of atorvastatin and 2-OH atorvastatin | AUCss,τ, Css,max | from pre dosing to 24hr post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate PK interaction of amlodipine and valsartan | tss,max, CLss/F, Css,min | from pre dosing to 24hr post dose | 
| To Evaluate PK interaction of atorvastatin and 2-OH atorvastatin | tss,max, CLss/F, Css,min | from pre dosing to 24hr post dose |