Pharmacokinetics, Safety and Tolerability of CKD-387 10/500mg BE Phase1

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics, safety and tolerability of CKD-387

Detailed Description
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An open-label, randomized, single-dose crossover study to evaluate the pharmacokinetics, safety and tolerability of CKD-387 in helalthy subjects.

Official Title
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An Open-label, Rendomized, Single-dose Crossover Study to Evaluate the Pharmacokinetics, Safety and Tolerability of CKD-387 in Healthy Subjects.

Conditions
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Type2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Part A, Reference (D635 10/500mg, Astrazeneca)
* Drug: Part A, Reference (D635 10/500mg, Astrazeneca)
* Drug: Part B, Reference (D635 10/500mg, Astrazeneca)
* Drug: Part B, Reference (D635 10/500mg, Astrazeneca)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult older than 19 years and less than 45 years at the time of screening. BMI 18.5 29.9 kg/m2 and body weight more than 50kg. Subjects who have consented to the use of appropriate double- pregnancy contraceptive methods up to one months after the last investigational product and not to provide sperm for men. Subjects who sign on an informed consent form willingly. Exclusion Criteria: Subjects who have a clinically significant disease or medical history such as respiratory, hepatic, kidneys, blood, gastrointestinal, endocrine, immune system, skin, nervous and mental disease. Subjects who have acute disease within 28 days prior to the first administration. Subjects who have history that may affect the ADME. Subjects who have medical history or medical abuse history of hypersensitivity from SGLT inhibitors or Biguanides including Metformin or other medications(Aspirin, Antibiotics etc.). Subjects who have clinically significant chronic disease. Subjects with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose mal-absorption. Subjects whose laboratory test result are same as below; AST,ALT > UNL(Upper Normal Limit)x3 Fasting glucose level out of 70-125mg/dl Creatinine clearance is lower than 80mL/min which is calcuated by Cockcroft-Gault formulation. QT>450msec Positive urine hCG(female). Subjects whoes blood pressure exceeds out of normal range as below at screening. SBP : over 100mmHg, under 160mmHg DBP : over 60mmHg, under 100mmHg Subjects who have been found to be positive in serological tests(HBs antigen, HCV antibody and HIV antibody). Subjects who took ETC(Ethical Drug), oriental medicine within 2 weeks prior to the first administration of investigational products. Subjects who took OTC(Over-the-counter Drug, including korean galenical drug) within 10 days prior to the first administration of investigational products. Subjects who have allergic disease which has clinical significance(But, light allergic rhinitis and ligth allergic dermatitis which do not need medication is exceptional). Subjects who can not eat standard meals provided by the institution. Subjects who donated whole blood within 60 days, donated the blood components within 20 days prior to the first administration of investigational products. Subjects who received blood transfusion within 30 days prior to the first administration of investigational products. Subjects who were participated in the other clinical trial within 90 days prior to the first administration of investigational products. Subjects who took medication for the induction and inhibition of metabolizing enzymes such as barbiturate drugs within 6months prior to the first administration of investigational products. Subjects who have had abnormal diets that can affect the ADME of the drug within 30 days prior to the first administration of investigational products. (Ingestion of grapefruit juice>1L/day or Caffein>5Cups/day). Subjects who have took regular alcohol(alcohol>30g/day) prior to the first administration of investigational products. Subjects who smoked more than 10 cigarettes per day prior 3months to the first administration of investigational products or cannot discontinue smoking during the clinical trial. Subjects who is determined unsuitable to participate in this clinical trial by the investigator. Lactating Women.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 part, 2x2 crossover study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PartA, Treatment-1<br>Period 1 : Reference drug Period 2 : Test drug | Drug: Part A, Reference (D635 10/500mg, Astrazeneca)<br>* Once a day. Under fasting condition<br>* Other names: PartA, Test(CKD-387 10/500mg);|
| Experimental: PartA, Treatment-2<br>Period 1 : Test drug Period 2 : Reference drug | Drug: Part A, Reference (D635 10/500mg, Astrazeneca)<br>* Once a day. Under fasting condition<br>* Other names: PartA, Test(CKD-387 10/500mg);|
| Experimental: PartB, Treatment-1<br>Period 1 : Reference drug Period 2 : Test drug | Drug: Part B, Reference (D635 10/500mg, Astrazeneca)<br>* Once a day. Under fed condition<br>* Other names: PartB, Test(CKD-387 10/500mg);|
| Experimental: PartB, Treatment-2<br>Period 1 : Test drug Period 2 : Reference drug | Drug: Part B, Reference (D635 10/500mg, Astrazeneca)<br>* Once a day. Under fed condition<br>* Other names: PartB, Test(CKD-387 10/500mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A : Cmax under fasting condition | Maximum concentration of the dapagliflozin | 0(predose) 48 hours | 
| Part A : Cmax under fasting condition | Maximum concentration of the metformin | 0(predose) 48 hours | 
| Part A : AUClast under fasting condition | Area Under Curve(last) of the dapagliflozin | 0(predose) 48 hours | 
| Part A : AUClast under fasting condition | Area Under Curve(last) of the metformin | 0(predose) 48 hours | 
| Part B : Cmax under fed condition | Maximum concentration of the metformin | 0(predose) 48 hours | 
| Part B : AUClast under fed condition | Area Under Curve(last) of the metformin | 0(predose) 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A : AUCinf under fasting condition | Area Under Curve(infinit) of the dapagliflozin | 0(predose) 48 hours | 
| Part A : AUCinf under fasting condition | Area Under Curve(infinit) of the metformin | 0(predose) 48 hours | 
| Part A : Tmax under fasting condition | Time of maximum concentration of the dapagliflozin | 0(predose) 48 hours | 
| Part A : Tmax under fasting condition | Time of maximum concentration of the metformin | 0(predose) 48 hours | 
| Part A : t1/2 under fasting condition | Half life of the dapagliflozin | 0(predose) 48 hours | 
| Part A : t1/2 under fasting condition | Half life of the metformin | 0(predose) 48 hours | 
| Part B : AUCinf under fed condition | Area Under Curve(infinit) of the metformin | 0(predose) 48 hours | 
| Part B : Tmax under fed condition | Time of Maximum concentration of the metformin | 0(predose) 48 hours | 
| Part B : t1/2 under fed condition | Half life of the metformin | 0(predose) 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type2 Diabetes Mellitus, CKD-387