A Clinical Trial to Investigate the Pharmacokinetic Drug Interaction and Safety of CKD-501, D745 and D150

Study Overview
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Brief Summary
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A Clinical trial to investigate the pharmacokinetic drug interaction and safety of CKD-501, D745 and D150

Detailed Description
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A Randomized, Open-label, Multiple-dose, Crossover Clinical Trial to Investigate the Pharmacokinetic Drug Interactions and Safety after Oral Administration of D745, D150 and CKD-501 in Healthy Adults

Official Title
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A Randomized, Open-label, Multiple-dose, Crossover Clinical Trial to Investigate the Pharmacokinetic Drug Interactions and Safety After Oral Administration of D745, D150 and CKD-501 in Healthy Adults

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: CKD-501
* Drug: D745, D150
* Drug: CKD-501, D745, D150


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult volunteers aged between 19 and 55-year-old Weight ≥ 55kg (men) or ≥ 50kg (women), with calculated body mass index(BMI) of 18.5 to 27.0 kg/m2 Women must meet one of the criteria written below: Menopause (No menstruation for 2 years) Sterilization (Hysterectomy or Oophorectomy, Tubal ligation etc.) Men agree to contraception & won't donate sperm during the participation of clinical trial Those who voluntarily decide to participate and agree to comply with the cautions after hearing and fully understanding the detailed description of this clinical trial Exclusion Criteria: Those who have clinically significant disease or medical history of Hepatopathy, Renal dysfunction, Neurological disorder, Immunity disorder, Respiratory disorder, Genitourinary system disorder, Digestive system disorder, Endocrine system disorder, Cardiovascular disorder, Blood tumor, Psychical disorder, Severe urinary tract infection Those who have clinically significant dehydration or vulnerable to dehydration by poor oral intake Those who receive intravenous administration of radioactive iodine contrast agents (for intravenous urography, venous cholangiography, angiography, computed tomography using contrast agents, etc.) within 48 hours before the first administration of investigational product Those who have genetic problems such as galactose intolerance, Lapp lactose deficiency or glucose-galactose malabsorption Those who have past medical history of gastrointestinal disorder (Crohn's disease, ulcerative colitis, etc. except simple appendectomy or hernia surgery), which affect the absorption of drug Those who have history of hypersensitivity to active pharmaceutical ingredient (Lobeglitazone, Empagliflozin, Metformin) or additives. Those who have the test results written below AST, ALT > 1.25 times higher than upper normal level Total bilirubin > 1.5 times higher than upper normal level eGFR (estimated Glomerular Filtration Rate, which is calculated by MDRD) < 60 mL/min/1.73m2 Positive or Reactive test result of Hepatitis B & C, HIV, RPR Under 5 min resting condition, systolic blood pressure >150 mmHg or <90 mmHg, diastolic blood pressure >100 mmHg or <50 mmHg Those who have a drug abuse history within one year or positive reaction on urine drug screening test Those who received following drugs, which may affect results of clinical trial and safety Ethical-the-counter (ETC) drugs and herbal medicines within 14 days before the first administration of the investigational drug Over-the-counter (OTC) drugs, health foods and vitamin preparations within 7 days before the first administration of the investigational product Those who take barbiturate and related (causing induction or inhibition of metabolism) drug within 1 month before the first administration of investigational product Those who exceeding an alcohol and smoke consumption criteria or can't stop smoking, consuming alcohol and caffeine during hospitalization period Criteria: Caffeine > 5 cups/day, Alcohol > 210 g/week, Smoke > 10 cigarettes/day Those who took grapefruit before the first administration of investigational product or can't stop taking grapefruit during hospitalization period Those who received investigational product by participating in other clinical trial within 6 months before the first administration of investigational product Those who donated whole blood within 2 months or apheresis within 1 month Those who received transfusion within 1 month Those who are pregnant or breastfeeding Those who are deemed inappropriate to participate in clinical trial by investigators

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Period 1: CKD-501 - A single oral dose of 1 tablet under fasting conditions for 5 days. Period 2: CKD-501, D745, D150 - A single oral dose of 4 tablets under fasting conditions for 5 days (CKD-501: 1 tablet, D745: 1 tablet, D150: 2 tablets). | Drug: CKD-501<br>* QD, PO<br>Drug: CKD-501, D745, D150<br>* QD, PO<br>|
| Experimental: Sequence 2<br>Period 1: CKD-501, D745, D150 - A single oral dose of 4 tablets under fasting conditions for 5 days (CKD-501: 1 tablet, D745: 1 tablet, D150: 2 tablets). Period 2: CKD-501 - A single oral dose of 1 tablet under fasting conditions for 5 days | Drug: CKD-501<br>* QD, PO<br>Drug: CKD-501, D745, D150<br>* QD, PO<br>|
| Experimental: Sequence 3<br>Period 1: D745, D150 - A single oral dose of 3 tablets under fasting conditions for 5 days (D745: 1 tablet, D150: 2 tablets). Period 2: CKD-501, D745, D150 - A single oral dose of 4 tablets under fasting conditions for 5 days (CKD-501: 1 tablet, D745: 1 tablet, D150: 2 tablets). | Drug: D745, D150<br>* QD, PO<br>Drug: CKD-501, D745, D150<br>* QD, PO<br>|
| Experimental: Sequence 4<br>Period 1: CKD-501, D745, D150 - A single oral dose of 4 tablets under fasting conditions for 5 days (CKD-501: 1 tablet, D745: 1 tablet, D150: 2 tablets). Period 2: D745, D150 - A single oral dose of 3 tablets under fasting conditions for 5 days (D745: 1 tablet, D150: 2 tablets). | Drug: D745, D150<br>* QD, PO<br>Drug: CKD-501, D745, D150<br>* QD, PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax,ss of CKD-501, D745, D150 | Cmax,ss: Maximum concentration of drug in plasma at steady state | Day 1, Day 3, Day 4 - Pre-dose (0 hour) / Day 5 - Pre-dose (0 hour), 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours | 
| AUCtau,ss of CKD-501, D745, D150 | AUCtau,ss: Area under the plasma drug concentration-time curve within a dosing interval(τ) at steady state | Day 1, Day 3, Day 4 - Pre-dose (0 hour) / Day 5 - Pre-dose (0 hour), 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmin,ss of CKD-501, D745, D150 | Cmin,ss: Minimum concentration of drug in plasma at steady state | Day 1, Day 3, Day 4 - Pre-dose (0 hour) / Day 5 - Pre-dose (0 hour), 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours | 
| Tmax,ss of CKD-501, D745, D150 | Tmax,ss: Time to maximum plasma concentration at steady state | Day 1, Day 3, Day 4 - Pre-dose (0 hour) / Day 5 - Pre-dose (0 hour), 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours | 
| CLss/F of CKD-501, D745, D150 | CLss/F: Apparent Clearance at steady state | Day 1, Day 3, Day 4 - Pre-dose (0 hour) / Day 5 - Pre-dose (0 hour), 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours | 
| Fluctuation of CKD-501, D745, D150 | Fluctuation: Peak trough fluctuation within one dosing interval | Day 1, Day 3, Day 4 - Pre-dose (0 hour) / Day 5 - Pre-dose (0 hour), 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24 hours |