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

Phase 1

Completed

• Conditions: Dyslipidemias
• Interventions: Dietary Supplement: High fat diet; Drug: CKD-337

• Registration Number: NCT03382756
• Lead Sponsor: Chong Kun Dang Pharmaceutical

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.

Study Timeline

• Study Start: 2017-10-12
• Primary Completion: 2017-11-02
• Study Completion: 2017-11-07
• Status Verified: 2017-12
• Study First Submitted: 2017-12-19
• Study First Submitted QC: 2017-12-19
• Last Update Submitted: 2017-12-25
• Study First Posted: 2017-12-26
• Last Update Posted: 2017-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 16

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group B	High fat diet	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
Group A	High fat diet	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
Group A	CKD-337	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
Group B	CKD-337	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

Primary Outcome Measures

Name	Time	Method
AUC0-t 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	Area under the plasma concentration of Atorvastatin versus time curve from time zero to time of last quantifiable concentration
Cmax 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	Maximum plasma concentration of Fenofibric acid
Cmax 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	Maximum plasma concentration of Atorvastatin
AUCt 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	Area under the plasma concentration of Fenofibric acid versus time curve from time zero to time of last quantifiable concentration

Secondary Outcome Measures

Name	Time	Method
CL/F 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	Total body clearance of Atorvastatin
Vd/F 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	Apparent volume of distribution of Atorvastatin
AUCinf 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	Area under the plasma concentration of Fenofibric acid versus time curve from time zero to time infinity
T 1/2 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	Apparent terminal half-life of Fenofibric acid
AUC0-t 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	Area under the plasma concentration of 2-hydroxy atorvastatin versus time curve from time zero to time of last quantifiable concentration
AUCinf 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	Area under the plasma concentration of Atorvastatin versus time curve from time zero to time infinity
T 1/2 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	Apparent terminal half-life of Atorvastatin
Tmax 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	Time to maximum concentration of Fenofibric acid
Cmax 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	Maximum concentration attained of 2-hydroxy atorvastatin
Tmax 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	Time to maximum concentration 2-hydroxy atorvastatin
Vd/F 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	Apparent volume of distribution of 2-hydroxy atorvastatin
CL/F 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	Total body clearance of Fenofibric acid
CL/F 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	Total body clearance of 2-hydroxy atorvastatin
Tmax 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	Time to maximum concentration of of Atorvastatin
Vd/F 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	Apparent volume of distribution of Fenofibric acid
AUCinf 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	Area under the plasma concentration of 2-hydroxy atorvastatin versus time curve from time zero to time infinity
T 1/2 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	Apparent terminal half-life of 2-hydroxy atorvastatin

Trial Locations

Locations (1)

Dong-A University Hospital; 🇰🇷 Busan, Seo-gu, Korea, Republic of