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

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

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

Study Overview

• Status: Completed
• Conditions: Dyslipidemias
• Intervention / Treatment: Dietary supplement: High fat diet; Drug: CKD-337

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seo-gu
    • Busan, Seo-gu, Korea, Republic of, 602-812
      • Dong-A University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male subjects between the ages of 19 and 45 years
2. Body mass index between 17.5 and 30.5 kg/m², body weight more than 55kg
3. Subject who doesn't have chronic disease, pathological symptoms or findings
4. 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
5. 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:

1. 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
2. Subject who has a history of gastrointestinal disease or gastrointestinal surgery which can affect drug absorption
3. Subject who has hypersensitivity to the drugs containing choline fenofibrate, fenofibrate or atorvastatin, or other drugs such as aspirin, fenofibrate series, antibiotics

4. 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

5. 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)
6. 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
7. History of drug abuse or a positive reaction for drug abuse examined by urinalysis at the time of screening
8. 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
9. Those who has experienced photoallergy or phototoxicity during treatment with fibrates or ketoprofen
10. 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
11. Subject who took the medication involved in other clinical trials within 3 months prior to the first dose of medication
12. 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
13. 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
14. Smoker(> 10 cigarettes/day) for the last 3 months or who can not stop smoking during the clinical trial
15. 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)
16. 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
17. Subject who do not use a reliable contraception or who plans a pregnancy during the clinical trial
18. Subject who has unsuitable conditions decided by investigator's judgement including clinical laboratory result

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; 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; A diet consisting of more than 900kcal and 35% of fat; Drug: CKD-337; Test Drug; Other Names: Atorvastatin Calcium Trihydrate + Choline Fenofibrate
EXPERIMENTAL: Group B; 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; A diet consisting of more than 900kcal and 35% of fat; Drug: CKD-337; Test Drug; 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

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Principal Investigator: Min Kyu Park, Professor, Dong-A University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 12, 2017
• Primary Completion (ACTUAL): November 2, 2017
• Study Completion (ACTUAL): November 7, 2017

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (ACTUAL): December 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 27, 2017
• Last Update Submitted That Met QC Criteria: December 25, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Gastrointestinal Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Nootropic Agents; Lipotropic Agents; Atorvastatin; Choline; Fenofibrate
• Other Study ID Numbers: 146FDI17001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No