Pharmacokinetics and Safety/Tolerability After Oral Administration of CKD-387 and D484 in Healthy Adults

Study Overview
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Brief Summary
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Randomized, Open-label, Single-dose, Two-way Crossover Clinical Trial to Investigate the Pharmacokinetics and Safety/Tolerability after Oral Administration of CKD-387 10/1000 mg and D484 10/1000mg in Healthy Adults

Official Title
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A Randomized, Open-label, Single-dose, Two-way Crossover Clinical Trial to Investigate the Pharmacokinetics and Safety/Tolerability After Oral Administration of CKD-387 10/1000 mg and D484 10/1000mg in Healthy Adults

Conditions
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Type II Diabetes

Intervention / Treatment
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* Drug: CKD-387
* Drug: D484


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers between the ages of 19 and 55 Body weight ≥ 55kg for male, ≥ 50kg for female Body mass index ≥ 18.5 kg/m2 and < 25.0 kg/m2 Females who are post-menopausal or underwent sterilization Males who agreed to practice contraception until after 28 days of last intake Investigational product Ability to provide written informed consent Exclusion Criteria: Subject with clinically significant hepatic, renal, nervous, immune, respiratory, endocrine, hemato-oncology, cardiovascular systemic disease and psychosis disorder Subject who are weak in dehydration or clinically significant dehydration IV injecting examination of radioactive-iodine substances within 48 hours prior to first IP administration Subjects who have Galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Subjects with history of gastrointestinal disease or surgery that may affect absorption of IP Hypersensitive to dapagliflozin/metformin At screening, AST(Aspartate Transaminase), ALT(Alanine Transaminase) > UNL(upper normal limit)*1.25 Total Bilirubin > UNL(upper normal limit)*1.5, CPK > UNL(upper normal limit)*1.5 eGFR(estimated Glomerular Filtration Rate) < 60 mL/min/1.73m2(Modification of diet in renal Disease calculated) Positive reaction on following tests: Hepatitis B, Hepatitis C, HIV(Human Immunodeficiency Virus) and syphilis SBP(Systolic blood pressure) ≥ 150 mmHg or < 90 mmHg, DBP(Diastolic blood pressure) > 100 mmHg or < 50 mmHg History of drug abuse or positive urine drug screening results Women with pregnant, breast-feeding Caffeine > 5 cups/day, Alcohol > 210 g/week, Smoker > 10 cigarettes /day or who are unable to stop caffeine intake, drinking alcohol and smoking until the last blood drawing for PK Subject who took ethical drug/herbal compound within 14 days, over-the-counter drug/vitamin supplements within 7 days and depot injection/implantation within 30 days prior to the first IP administration Subject who was enrolled in another clinical trial(including Bioequivalence study) and administered drugs within 90 days prior to the first IP administration Subject with whole blood donation within 60 days or component blood donation within 30 days Not eligible to participate for the study at the discretion of Investigator

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: Group 1<br>Period 1: 1 tablet of reference drug(D484) Period 2: 1 tablet of test drug(CKD-387) | Drug: CKD-387<br>* test drug<br>Drug: D484<br>* reference drug<br>|
| Experimental: Group 2<br>Period 1: 1 tablet of test drug(CKD-387) Period 2: 1 tablet of reference drug(D484) | Drug: CKD-387<br>* test drug<br>Drug: D484<br>* reference drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Dapagliflozin | Maximum plasma concentration of Dapagliflozin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| Cmax of Metformin | Maximum plasma concentration of Metformin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| AUClast of Dapagliflozin | Area under the plasma concentration-time curve to last concentration of Dapagliflozin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| AUClast of Metformin | Area under the plasma concentration-time curve to last concentration of Metformin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf of Dapagliflozin | Area under the plasma concentration-time curve from zero to infinity concentration of Dapagliflozin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| AUCinf of Metformin | Area under the plasma concentration-time curve from zero to infinity concentration of Metformin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| Tmax of Dapagliflozin | Time to maximum plasma concentration of Dapagliflozin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| Tmax of Metformin | Time to maximum plasma concentration of Metformin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| T1/2 of Dapagliflozin | Half-life of Dapagliflozin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| T1/2 of Metformin | Half-life of Metformin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| Vd/F of Dapagliflozin | Apparent volume of distribution of Dapagliflozin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| Vd/F of Metformin | Apparent volume of distribution of Metformin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| CL/F of Dapagliflozin | Apparent clearance of Dapagliflozin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration | 
| CL/F of Metformin | Apparent clearance of Metformin | Predose(0h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, and 48 hour after drug administration |