CKD-337(2) Drug-drug Interaction Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetic interaction between Atorvastatin and Fenofibric acid.

Detailed Description
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This study is a randomized, open-label, multiple dosing, 3-way crossover design to evaluate the drug-drug interaction between Atorvastatin (Lipitor) and Fenofibric (Trilipix) acid in healthy male subjects. Subjects will receive repeated dose of Atorvastatin (40mg*1Tab/day) or Fenofibric acid (135mg*1Cap/day) or Atorvastatin (40mg*1Tab/day)/Fenofibric acid (135mg*1Cap/day). Each treatment period was separated by a washout period of at least 8 days.

Official Title
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A Randomized, Open-label, Multiple Dosing, 3-way Crossover Study to Evaluate the Drug-drug Interaction Between Atorvastatin and Fenofibric Acid in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lipitor Tab. 40mg
* Drug: Trilipix 135mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy man older than 19 years at the time of screening. BMI more than 17.5kg / m2 and less than 30.5kg / m2 and weight more than 55kg Subject without congenital or chronic diseases and no psychotic symptoms or findings from the medical examination. Suitable subject who is determined by laboratory tests such as hematology tests, blood chemistry, urinalysis test according to the characteristics of the drug and screening tests such as ECG test. Subject who fully understand the clinical trials after in-depth explanation given prior to the clinical study, decided to join the clinical trials by their will and signed consent form which approved by Chonbuk National University Hospital IRB. Subjects who are able to comply with all scheduled visits, laboratory tests and other procedures. Exclusion Criteria: Subject who has a history of blood, kidneys, endocrine, respiratory, gastrointestinal, urinary, cardiovascular, hepatic, psychiatric, neurological or allergic diseases that is clinically significant (Except untreated asymptomatic seasonal allergies at the time of administration) Subject who has a history of gastrointestinal disease or gastrointestinal surgery which can affect drug absorption. Showing the value that corresponds to following laboratory parameters: AST or AST or CK > 2* upper limit of normal range. Alcohol > 210g/week, within 6 months prior to the screening. Taking the medication involved in other clinical trials within two months before the first dose medication characters. Sitting Systolic Blood Pressure ≥ 140 mmHg, Diastolic Blood Pressure ≥ 90 mmHg at the time of screening. History of alcohol or drug abuse, within 1 year Subjects who treated with metabolizing enzyme inducers or inhibitors such as barbitals within 30days prior to the first dosing. Smoker (> 20cigarettes/day) Subjects who takes ETC or OTC medicine within 10days before the first IP administration. Subject who done the whole blood donation within two months or component blood donation within 1 month within 1 month prior to the first dosing. Subject who can increase risk due to clinical test and administration of drugs or has Severe grade / chronic medical, mental condition or abnormal laboratory result that may interfere with the analysis of test results. Subject with serious history of hypersensitivity or allergy to investigational product. Active liver disease. Muscle disease. Subject with genetic problems such as galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption. Patients with severe hepatic impairment or Gallbladder Disease. Patients with moderate to severe renal impairment. Patients experienced allergy or phototoxicity during treatment with fibrate or ketoprofen. Subjects who is not able to comply with guidelines described in the protocol. Subjects who is determined by investigator's decision as unsuitable for clinical trial participation.

Ages Eligible for Study
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Minimum Age: 19 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group1: TreatmentA+TreatmentB+TreatmentC<br>TreatmentA: Atorvastatin 40m*1T/day, TreatmentB: Fenofibric acid 135mg*1Cap/day, TreatmentC: Atorvastatin 40m*1T/day and Fenofibric acid 135mg*1Cap/day. Each treatment period was separated by a washout period of at least 8days. | Drug: Lipitor Tab. 40mg<br> <br> * Other names: Atorvastatin 40mg;Drug: Trilipix 135mg<br> <br> * Other names: Fenofibric acid 135mg;|
| Experimental: Group2: TreatmentC+TreatmentA+TreatmentB<br>TreatmentA: Atorvastatin 40m*1T/day, TreatmentB: Fenofibric acid 135mg*1Cap/day, TreatmentC: Atorvastatin 40m*1T/day and Fenofibric acid 135mg*1Cap/day. Each treatment period was separated by a washout period of at least 8days. | Drug: Lipitor Tab. 40mg<br> <br> * Other names: Atorvastatin 40mg;Drug: Trilipix 135mg<br> <br> * Other names: Fenofibric acid 135mg;|
| Experimental: Group3: TreatmentB+TreatmentC+TreatmentA<br>TreatmentA: Atorvastatin 40m*1T/day, TreatmentB: Fenofibric acid 135mg*1Cap/day, TreatmentC: Atorvastatin 40m*1T/day and Fenofibric acid 135mg*1Cap/day. Each treatment period was separated by a washout period of at least 8days. | Drug: Lipitor Tab. 40mg<br> <br> * Other names: Atorvastatin 40mg;Drug: Trilipix 135mg<br> <br> * Other names: Fenofibric acid 135mg;|
| Experimental: Group4: TreatmentC+TreatmentB+TreatmentA<br>TreatmentA: Atorvastatin 40m*1T/day, TreatmentB: Fenofibric acid 135mg*1Cap/day, TreatmentC: Atorvastatin 40m*1T/day and Fenofibric acid 135mg*1Cap/day. Each treatment period was separated by a washout period of at least 8days. | Drug: Lipitor Tab. 40mg<br> <br> * Other names: Atorvastatin 40mg;Drug: Trilipix 135mg<br> <br> * Other names: Fenofibric acid 135mg;|
| Experimental: Group5: TreatmentB+TreatmentA+TreatmentC<br>TreatmentA: Atorvastatin 40m*1T/day, TreatmentB: Fenofibric acid 135mg*1Cap/day, TreatmentC: Atorvastatin 40m*1T/day and Fenofibric acid 135mg*1Cap/day. Each treatment period was separated by a washout period of at least 8days. | Drug: Lipitor Tab. 40mg<br> <br> * Other names: Atorvastatin 40mg;Drug: Trilipix 135mg<br> <br> * Other names: Fenofibric acid 135mg;|
| Experimental: Group6: TreatmentA+TreatmentC+TreatmentB<br>TreatmentA: Atorvastatin 40m*1T/day, TreatmentB: Fenofibric acid 135mg*1Cap/day, TreatmentC: Atorvastatin 40m*1T/day and Fenofibric acid 135mg*1Cap/day. Each treatment period was separated by a washout period of at least 8days. | Drug: Lipitor Tab. 40mg<br> <br> * Other names: Atorvastatin 40mg;Drug: Trilipix 135mg<br> <br> * Other names: Fenofibric acid 135mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atorvastatin and Fenofibric acid AUCτ | 1D 7D 19points, 1D 7D 18points, 1D 7D 20points | predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose, an expected average of 6weeks | 
| Atorvastatin and Fenofibric acid Css,max | 1D 7D 19points, 1D 7D 18points, 1D 7D 20points | predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose, an expected average of 6weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atorvastatin and Fenofibric acid Css,min | 1D 7D 19points, 1D 7D 18points, 1D 7D 20points | predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose, an expected average of 6weeks | 
| Atorvastatin and Fenofibric acid Css,av | 1D 7D 19points, 1D 7D 18points, 1D 7D 20points | predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose, an expected average of 6weeks | 
| 2-hydroxyatorvastatin AUCτ | 1D 7D 19points, 1D 7D 18points, 1D 7D 20points | predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose, an expected average of 6weeks | 
| 2-hydroxyatorvastatin Css,max | 1D 7D 19points, 1D 7D 18points, 1D 7D 20points | predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose, an expected average of 6weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Male Volunteers