Clinical trial NCT03382756: A Clinical Trial to Assess the Effects of Food on the Bioavailability of CKD-337
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dyslipidemias
Lead sponsor: Chong Kun Dang Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2017-12-26
Enrollment: 16
Sex: MALE
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: AUC0-t of Atorvastatin
timeFrame: 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
measure: Cmax of Atorvastatin
timeFrame: 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
measure: AUCt of Fenofibric acid
timeFrame: Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration
measure: Cmax of Fenofibric acid
timeFrame: 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 outcomes:
measure: AUCinf of Atorvastatin
timeFrame: 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
measure: Tmax of Atorvastatin
timeFrame: 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
measure: T 1/2 of Atorvastatin
timeFrame: 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
measure: CL/F of Atorvastatin
timeFrame: 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
measure: Vd/F of Atorvastatin
timeFrame: 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
measure: AUCinf of Fenofibric acid
timeFrame: Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration
measure: Tmax of Fenofibric acid
timeFrame: Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration
measure: T 1/2 of Fenofibric acid
timeFrame: Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration
measure: CL/F of Fenofibric acid
timeFrame: Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration
measure: Vd/F of Fenofibric acid
timeFrame: Predose(0hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96hr after drug administration
measure: AUC0-t of 2-hydroxy atorvastatin
timeFrame: 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
measure: Cmax of 2-hydroxy atorvastatin
timeFrame: 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
measure: AUCinf of 2-hydroxy atorvastatin
timeFrame: 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
measure: Tmax of 2-hydroxy atorvastatin
timeFrame: 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
measure: T 1/2 of 2-hydroxy atorvastatin
timeFrame: 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
measure: CL/F of 2-hydroxy atorvastatin
timeFrame: 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
measure: Vd/F of 2-hydroxy atorvastatin
timeFrame: 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
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
state: Seo-gu
Study officials:
affiliation: Dong-A University Hospital
name: Min Kyu Park, Professor
role: PRINCIPAL_INVESTIGATOR
References: