A Clinical Trial to Assess the Effects of Food on the Bioavailability of CKD-337

Study Overview
=================
Brief Summary
-----------------
A cross-over, randomized and open-label clinical trial to evaluate the effects of food on the bioavailability of CKD-337 after a single oral dose in healthy male subjects

Detailed Description
-----------------
This clinical trial is to evaluate the effects of food on pharmacokinetics of CKD-337. Sixteen male subjects are divided into two groups. A group of subjects are administered a single oral dose of CKD-337 after ingesting high fat meal and the other take same investigational product (IP) in fasting condition. Then their blood is drawn on a fixed schedule to analyse bioavailability of CKD-337. Finishing the first treatment period, the two groups switch food conditions and initiate the second period. The group of people that were administered CKD-337 with food are then dosed the same IP in fasting condition, and the other group undergo vice versa. Each treatment period was separated by a washout period of at least 7 days.

Official Title
-----------------
A Cross-over, Randomized and Open-label Clinical Trial to Evaluate the Effects of Food on the Bioavailability of CKD-337 After a Single Oral Dose in Healthy Male Subjects

Conditions
-----------------
Dyslipidemias

Intervention / Treatment
-----------------
* Dietary Supplement: High fat diet
* Drug: CKD-337


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male subjects between the ages of 19 and 45 years Body mass index between 17.5 and 30.5 kg/m², body weight more than 55kg Subject who doesn't have chronic disease, pathological symptoms or findings Subject who is suitable for the clinical trial determined by laboratory tests(serum test, hematology test, blood chemistry, urinalysis test etc.), Vital Sign, ECG test at the time of screening Subject who fully understand the clinical trial after in-depth explanation, decide to join the clinical trials and sign on an inform consent from willingly. Exclusion Criteria: Subject who has a clinically significant disease such as hepatic, kidneys, neurological, respiratory, endocrine, hemato-oncology, urinary, cardiovascular, musculoskeletal or psychiatric diseases and who has medical histories listed below. Gallbladder disease including cholelithiasis, severe hepatic impairment Acute/chronic pancreatitis due to hypertriglyceridemia Pulmonary embolism or interstitial lung disease Genetic problems such as galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Hypoalbuminemia Alcoholics 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 drugs containing choline fenofibrate, fenofibrate or atorvastatin, or other drugs such as aspirin, fenofibrate series, antibiotics Subject who has the following clinical significant findings in the EKG at the time of screening QTc(Q-T interval corrected for heart rate) > 450ms PR interval(The interval between the beginning of the P wave and the beginning of the QRS complex in ECG) > 200msec QRS duration(The duration of the QRS wave in ECG) > 120msec Subject whose results of the clinical laboratory tests are included in the following categories CPK(Creatinine Phospho-Kinase) > 2x upper limit of normal range Liver function test (AST;Aspartate Transaminase, ALT;Alanine Transaminase, ALP;Alkaline phosphatase, Total bilirubin, γ-GT;Gamma-Glutamyl Transferase) > 2 x upper limit of normal range eGFR(Estimated Glomerular Filtration Rate) < 60 mL/min/1.73m² Calculated by MDRD(Modification of Diet in Renal Disease) Systolic blood pressure ≥ 160mmHg(millimeter of mercury) or ≤ 100mmHg(millimeter of mercury) , Diastolic blood pressure ≥ 95mmHg(millimeter of mercury) or ≤ 60mmHg(millimeter of mercury) at the time of screening History of drug abuse or a positive reaction for drug abuse examined by urinalysis at the time of screening Subject who took medicines that are known to significantly induce or inhibit drug metabolizing enzymes, including barbiturates, within 30 days prior to the first dose of medication Those who has experienced photoallergy or phototoxicity during treatment with fibrates or ketoprofen Subject who took ETC(Ethical Drug), oriental medicine within 2 weeks and OTC(Over-the-counter Drug), vitamin within 10 days prior to the first dose of medication Subject who took the medication involved in other clinical trials within 3 months prior to the first dose of medication Subject who donated whole conducted blood donation within 2 months or component blood donation or blood transfusion within 1 month prior to the first dose of medication Subject who drinks alcohol more than 21 units per a week (1unit=10g of pure alcohol) continuously within 6 month prior to the first dose of medication or Who can not stop drinking alcohol during the clinical trial Smoker(> 10 cigarettes/day) for the last 3 months or who can not stop smoking during the clinical trial Subject who consumed food containing grapefruit within 48 hours prior to the first dose of medication or who can not stop consumption it until EOS(End of study) Subject who consumed food containing caffeine(e.g. coffee, green tea etc.) within 24 hours prior to the first dose of medication or who can not stop consumption it until discharge Subject who do not use a reliable contraception or who plans a pregnancy during the clinical trial Subject who has unsuitable conditions decided by investigator's judgement including clinical laboratory result

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Period 1: 1 capsule of test drug(CKD-337) administered under fasting condition Period 2: 1 capsule of test drug(CKD-337) under high fat diet condition | Dietary Supplement: High fat diet<br>* A diet consisting of more than 900kcal and 35% of fat<br>Drug: CKD-337<br>* Test Drug<br>* Other names: Atorvastatin Calcium Trihydrate + Choline Fenofibrate;|
| Experimental: Group B<br>Period 1: 1 capsule of test drug(CKD-337) under high fat diet fed condition Period 2: 1 capsule of test drug (CKD-337) administered under fasting condition | Dietary Supplement: High fat diet<br>* A diet consisting of more than 900kcal and 35% of fat<br>Drug: CKD-337<br>* Test Drug<br>* Other names: Atorvastatin Calcium Trihydrate + Choline Fenofibrate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t of Atorvastatin | Area under the plasma concentration of Atorvastatin versus time curve from time zero to time of last quantifiable concentration | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| Cmax of Atorvastatin | Maximum plasma concentration of Atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| AUCt of Fenofibric acid | Area under the plasma concentration of Fenofibric acid versus time curve from time zero to time of last quantifiable concentration | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration | 
| Cmax of Fenofibric acid | Maximum plasma concentration of Fenofibric acid | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf of Atorvastatin | Area under the plasma concentration of Atorvastatin versus time curve from time zero to time infinity | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| Tmax of Atorvastatin | Time to maximum concentration of of Atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| T 1/2 of Atorvastatin | Apparent terminal half-life of Atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| CL/F of Atorvastatin | Total body clearance of Atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| Vd/F of Atorvastatin | Apparent volume of distribution of Atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| AUCinf of Fenofibric acid | Area under the plasma concentration of Fenofibric acid versus time curve from time zero to time infinity | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration | 
| Tmax of Fenofibric acid | Time to maximum concentration of Fenofibric acid | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration | 
| T 1/2 of Fenofibric acid | Apparent terminal half-life of Fenofibric acid | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration | 
| CL/F of Fenofibric acid | Total body clearance of Fenofibric acid | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration | 
| Vd/F of Fenofibric acid | Apparent volume of distribution of Fenofibric acid | Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration | 
| AUC0-t of 2-hydroxy atorvastatin | Area under the plasma concentration of 2-hydroxy atorvastatin versus time curve from time zero to time of last quantifiable concentration | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| Cmax of 2-hydroxy atorvastatin | Maximum concentration attained of 2-hydroxy atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| AUCinf of 2-hydroxy atorvastatin | Area under the plasma concentration of 2-hydroxy atorvastatin versus time curve from time zero to time infinity | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| Tmax of 2-hydroxy atorvastatin | Time to maximum concentration 2-hydroxy atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| T 1/2 of 2-hydroxy atorvastatin | Apparent terminal half-life of 2-hydroxy atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| CL/F of 2-hydroxy atorvastatin | Total body clearance of 2-hydroxy atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration | 
| Vd/F of 2-hydroxy atorvastatin | Apparent volume of distribution of 2-hydroxy atorvastatin | Predose(0hr), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48hr after drug administration |