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

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.

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: Lipitor + Lipidil supra; Drug: CKD-337

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male older than 19 years at the time of screening
2. BMI 17.5~30.5 kg/m2 and body weight more than 55kg
3. Subject who is no chronic disease, no symptoms or pathological findings
4. 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
5. 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:

1. 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
2. Subject who has a history of gastrointestinal disease or gastrointestinal surgery which can affect drug absorption
3. Subject who has hypersensitivity to the drug composition containing choline fenofibrate, fenofibrate or atorvastatin, and other drug(aspirin, fenofibrate series, antibiotic and so on)

4. The following clinical significant findings at the time of screening

   • QTc > 450ms
   • PR interval > 200msec
   • QRS duration > 120msec

5. 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
6. Systolic blood pressure ≥ 160mmHg or ≤ 100mmHg, Diastolic blood pressure ≥ 95mmHg or ≤ 60mmHg at the time of screening
7. History of drug abuse or a positive reaction for drug abuse at the screening test for urine
8. Taking ETC, oriental medicine within 2 weeks and OTC, vitamin within 1 week before the first dosing
9. Taking the medication involved in other clinical trials within 3 months before the first dosing
10. Whole blood donation with 2 months or component blood donation within 1 month or blood transfusion within 1 month before the first dosing
11. Alcohol > 21 units/week (1unit=10g of pure alcohol), within 6 month before the first dosing
12. Smoker(> 10 cigarettes/day) for the last 3 months
13. Comsumption of grapefruit of food containing grapefruit during clinical trial period from first dosing 48hours ago
14. Comsumption of food containing caffeine(e.g. coffee, green tea) during 24 hours ago IP dosing at discharge
15. Not using a reliable contraception, planning a pregnancy during the study
16. An impossible one who participates in clinical trial by investigator's decision including laboratory test result

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; 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; Reference Drug: Lipitor + Lipidil supra; Other Names: Lipitor(Atorvastatin calcium trihydrate 21.70mg/tablet) + Lipidil supra(Fenofibrate 160mg/tablet); Drug: CKD-337; Test Drug: CKD-337; Other Names: CKD-337(Atorvastatin calcium trihydrate 21.70mg+Cholinfe fenofibrate 178.8mg/capsule)
Experimental: B; 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; Reference Drug: Lipitor + Lipidil supra; Other Names: Lipitor(Atorvastatin calcium trihydrate 21.70mg/tablet) + Lipidil supra(Fenofibrate 160mg/tablet); Drug: CKD-337; Test Drug: CKD-337; Other Names: CKD-337(Atorvastatin calcium trihydrate 21.70mg+Cholinfe fenofibrate 178.8mg/capsule)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: January 8, 2016
• First Submitted That Met QC Criteria: January 8, 2016
• First Posted (Estimate): January 11, 2016

Study Record Updates

• Last Update Posted (Estimate): July 7, 2016
• Last Update Submitted That Met QC Criteria: July 5, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Atorvastatin; Calcium; Calcium, Dietary; Fenofibrate
• Other Study ID Numbers: 146BE15025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No