A Clinical Trial to Compare Safety and Pharmacokinetic Characteristics of CKD-337

Study Overview
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Brief Summary
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This study is a randomized, open-label, single oral dose, 2-way crossover clinical trial to compare safety and pharmacokinetics of CKD-337 in healthy male volunteers.

Detailed Description
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This study is a randomized, open-label, single oral dose, 2-way crossover clinical trial to compare safety and pharmacokinetics of CKD-337 in healthy male volunteers. Subjects will receive either a single oral dose of the test formulation(CKD-337) or a oral dose of the reference formulation(Lipitor+Lipidil supra). Each treatment period was separated by a washout period of at least 7 days.

Official Title
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A Randomized, Open-label, Single Oral Dose, 2-way Crossover Clinical Trial to Compare Safety and Pharmacokinetic Characteristics of CKD-337 in Healthy Male Volunteers.

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: Lipitor + Lipidil supra
* Drug: CKD-337


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male older than 19 years at the time of screening BMI 17.5 30.5 kg/m2 and body weight more than 55kg Subject who is no chronic disease, no symptoms or pathological findings Suitable subject who is determined by laboratory tests(hematology test, blood chemistry, urinalysis test) according to the characteristics of the drug and ECG test at the time of screening Subject who fully understand the clinical trials after in-depth explanation, decided to join the clinical trials by their will and signed inform consent Exclusion Criteria: Subject who has a history of hepatic, kidneys, neurological, respiratory, endocrine, hemato-oncology, urinary, cardiovascular, musculoskeletal or psychiatric diseases that is clinically significant and who has a following history 1) Gallbladder disease including cholelithiasis, severe hepatic impairment 2) Acute/chronic pancreatitis due to hypertriglyceridemia 3) Pulmonary embolism or interstitial lung disease 4) Genetic problems such as galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption 5) Hypoalbuminemia 6) Alcoholics 7) Predisposition to rhabdomyolysis Subject who has a history of gastrointestinal disease or gastrointestinal surgery which can affect drug absorption Subject who has hypersensitivity to the drug composition containing choline fenofibrate, fenofibrate or atorvastatin, and other drug(aspirin, fenofibrate series, antibiotic and so on) The following clinical significant findings at the time of screening QTc > 450ms PR interval > 200msec QRS duration > 120msec The following results in the clinical laboratory tests CPK > 2 x upper limit of normal range Liver function test (AST, ALT, ALP, Total bilirubin, γ-GT) > 2 x upper limit of normal range eGFR(estimated GFR) < 60 mL/min/1.73m2 Systolic blood pressure ≥ 160mmHg or ≤ 100mmHg, Diastolic blood pressure ≥ 95mmHg or ≤ 60mmHg at the time of screening History of drug abuse or a positive reaction for drug abuse at the screening test for urine Taking ETC, oriental medicine within 2 weeks and OTC, vitamin within 1 week before the first dosing Taking the medication involved in other clinical trials within 3 months before the first dosing Whole blood donation with 2 months or component blood donation within 1 month or blood transfusion within 1 month before the first dosing Alcohol > 21 units/week (1unit=10g of pure alcohol), within 6 month before the first dosing Smoker(> 10 cigarettes/day) for the last 3 months Comsumption of grapefruit of food containing grapefruit during clinical trial period from first dosing 48hours ago Comsumption of food containing caffeine(e.g. coffee, green tea) during 24 hours ago IP dosing at discharge Not using a reliable contraception, planning a pregnancy during the study An impossible one who participates in clinical trial by investigator's decision including laboratory test result

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: A<br>Period 1: Reference drug (Lipitor+ Lipidil supra), 2 tablets administered under fed conditions. Period 2: Test drug(CKD-337), 1 capsule administered under fed conditions. | Drug: Lipitor + Lipidil supra<br>* Reference Drug: Lipitor + Lipidil supra<br>* Other names: Lipitor(Atorvastatin calcium trihydrate 21.70mg/tablet) + Lipidil supra(Fenofibrate 160mg/tablet);Drug: CKD-337<br>* Test Drug: CKD-337<br>* Other names: CKD-337(Atorvastatin calcium trihydrate 21.70mg+Cholinfe fenofibrate 178.8mg/capsule);|
| Experimental: B<br>Period 1: Test drug(CKD-337), 1 capsule administered under fed conditions. Period 2: Reference drug (Lipitor+ Lipidil supra), 2 tablets administered under fed conditions. | Drug: Lipitor + Lipidil supra<br>* Reference Drug: Lipitor + Lipidil supra<br>* Other names: Lipitor(Atorvastatin calcium trihydrate 21.70mg/tablet) + Lipidil supra(Fenofibrate 160mg/tablet);Drug: CKD-337<br>* Test Drug: CKD-337<br>* Other names: CKD-337(Atorvastatin calcium trihydrate 21.70mg+Cholinfe fenofibrate 178.8mg/capsule);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atorvastatin AUCt |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| Atorvastatin Cmax |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| Fenofibric acid AUCt |  | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96hr after drug administration | 
| Fenofibric acid Cmax |  | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96hr after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atorvastatin AUCinf |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| Atorvastatin Tmax |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| Atorvastatin t1/2 |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| Atorvastatin CL/F |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| Atorvastatin Vd/F |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| Fenofibric acid AUCinf |  | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96hr after drug administration | 
| Fenofibric acid Tmax |  | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96hr after drug administration | 
| Fenofibric acid t1/2 |  | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96hr after drug administration | 
| Fenofibric acid CL/F |  | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96hr after drug administration | 
| Fenofibric acid Vd/F |  | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96hr after drug administration | 
| 2-hydroxy atorvastatin AUCt |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| 2-hydroxy atorvastatin Cmax |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| 2-hydroxy atorvastatin AUCinf |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| 2-hydroxy atorvastatin Tmax |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| 2-hydroxy atorvastatin t1/2 |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| 2-hydroxy atorvastatin CL/F |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration | 
| 2-hydroxy atorvastatin Vd/F |  | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48hr after drug administration |