Clinical Trial to Evaluate the Drug Drug Interaction of CKD-501 and D308

Study Overview
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Brief Summary
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Phase 1 trial to evaluate the drug drug interaction of CKD-501 and D308

Detailed Description
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A randomized, open-label, multiple dose, 2-way crossover study to evaluate the drug drug interaction of CKD-501 and D308 in healthy volunteers

Official Title
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A Randomized, Open-label, Multiple Dose, 2-way Crossover Study to Evaluate the Drug Drug Interaction of CKD-501 and D308 in Healthy Volunteers

Conditions
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Diabetes Mellitus, Type II

Intervention / Treatment
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* Drug: D308, CKD-501


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult older than 19 years at the time of screening BMI 17.5 30.5kg/m2 and body weight more than 55kg Subject who has no chronic disease within last 3 years and no symptoms or pathological findings Suitable subject who is determined to be suitable at the time of screening such as laboratory tests(hematology, blood chemistry, urinalysis, virus/bacteriological test, etc.), sign of vitality, electrocardiogram Subject who signed the written consent of the Chonbuk National University Hospital IRB to participate in this study with full understanding of the purpose and contents of the examination prior to the clinical trial Subject who has will and ability to participate in clinical trials Exclusion Criteria: Subject who has a history of clinical significant blood, kidney, endocrine, respiratory, gastrointestinal, urinary, cardiovascular, liver, psychiatric, neurological or allergic diseases(except for asymptomatic seasonal allergies not treated at the time of administration) or evidence(except for simple dental history such as dental calculus, impacted tooth, wisdom tooth, etc.) Subject with a history of gastrointestinal disorders(esophageal achalasia or esophagus stenosis, Crohn's disease) or gastrointestinal surgery(except for simple appendicitis surgery or hernia surgery or tooth extraction surgery) that may affect the absorption Clinical laboratory test results showing the following values * ALT or AST > 2 times upper limit of normal range Subject who has a history of regular alcohol consumption exceeding 210g/week within 6months of screening (1 glass of beer(5%)=10g, 1 glass of soju(20%)=8g, 1 glass of wine(12%)=12g) Those taking other clinical trial drugs or bioequivalence test drugs within 3months before the first administration of clinical trial drug Subject who has a systolic blood pressure of less than 100mmHg or more than 140mmHg or diastolic blood pressure of less than 60mmHg or more than 90mmHg of screening Subject who has significant alcohol abuse or drug abuse within a year of screening Those taking medication known to significantly induce or inhibit drug metabolizing enzymes within 30days prior to the first administration of clinical trial medication More than 20 smokers per day within six months of screening Those taking prescription or non-prescription drugs within 10days before the first administration of clinical trial medication Those who donated whole blood within 2 months or those who donated the components within 1 month before the first administration of the clinical trial drug Subject who has risk of serious or chronic medical, mental, or laboratory examinations that may increase the risk due to the administration of medicines for clinical trials and may interfere with the interpretation of test results Patients who are known to be hypersensitive to the drug or its components Patients with severe heart failure or heart failure(New York Heart Association(NYHA) Class 3, 4 heart patients) Patients with hepatic impairment Patients with a glomerular filtration rate(eGFR) less than 60ml/min/1.73m2, patients with end stage renal disease or dialysis Patients with diabetic ketoacidosis, diabetic coma and total coma, patients with type 1 diabetes Before and after surgery, severe infectious patients, severe trauma patients Subjects with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Pregnant and lactating women Subject who is judged by the investigator to be ineligible to participate in the clinical trial

Ages Eligible for Study
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Minimum Age: 19 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: Part 1: Group 1(Treatment A/Treatment B)<br>Period 1: Treatment A (D308 1T)/day for 5days, QD, PO Period 2: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO | Drug: D308, CKD-501<br>* D308 CKD-501: Lobeglitazone sulfate 0.5mg<br>|
| Experimental: Part 1: Group 2(Treatment B/Treatment A)<br>Period 1: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO Period 2: Treatment A (D308 1T)/day for 5days, QD, PO | Drug: D308, CKD-501<br>* D308 CKD-501: Lobeglitazone sulfate 0.5mg<br>|
| Experimental: Part 2: Group 1(Treatment C/Treatment B)<br>Period 1: Treatment C (CKD-501 1T)/day for 5days, QD, PO Period 2: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO | Drug: D308, CKD-501<br>* D308 CKD-501: Lobeglitazone sulfate 0.5mg<br>|
| Experimental: Part 2: Group 2(Treatment B/Treatment C)<br>Period 1: Treatment B (D308 1T + CKD-501 1T)/day for 5days, QD, PO Period 2: Treatment C (CKD-501 1T)/day for 5days, QD, PO | Drug: D308, CKD-501<br>* D308 CKD-501: Lobeglitazone sulfate 0.5mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part 1) AUCss,tau of D308 | Area under the curve of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) Css,max of D308 | Max Concentration of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) AUCss,tau of CKD-501 | Area under the curve of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) Css,max of CKD-501 | Max Concentration of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part 1) Css,min of D308 | Min concentration of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) Css,av of D308 | average concentration of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) Tss,max of D308 | time of Max concentration of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) t1/2 of D308 | half-life time of D308 | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) CLss/F of D308 | Apparent clearance of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) Vdss/F of D308 | Apparent volume of distribution of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) Fluctuation[(Css,max-Css,min)/Css,av] of D308 | Fluctuation concentration of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 1) Swing[(Css,max-Css,min)/Css,min] of D308 | Swing concentration of D308 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) Css,min of CKD-501 | Min concentration of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) Css,av of CKD-501 | average concentration of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) Tss,max of CKD-501 | time of Max concentration of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) t1/2 of CKD-501 | half-life time of CKD-501 | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) CLss/F of CKD-501 | Apparent clearance of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) Vdss/F of CKD-501 | Apparent volume of distribution of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) Fluctuation[(Css,max-Css,min)/Css,av] of CKD-501 | Fluctuation concentration of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 
| (Part 2) Swing[(Css,max-Css,min)/Css,min] of CKD-501 | Swing concentration of CKD-501 at steady state | Day 1, 3, 4 predose(0 hour) and Day 5 predose(0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type II