A Clinical Study to Compare the Pharmacokinetic Characteristics of CKD-395 0.25/750 mg in Healthy Male Volunteers

Study Overview
=================
Brief Summary
-----------------
This study is a randomized, open-label, single dose, 2-way crossover study to compare the pharmacokinetic characteristics of CKD-395 0.25/750 mg in healthy male volunteers.

Detailed Description
-----------------
To healthy male subjects of twenty six(26), following treatments are administered dosing in each period fed condition(high fat meals) and wash-out period is a minimum of 7 days. Treatment A(Reference Drug): DuvieTM Tab. 0.5mg 1T + Glucodaun OR Tab. 750mg 2T Treatment B(Test Drug): CKD-395 0.25/750mg Tab. 2T Pharmacokinetic blood samples are collected up to 48hrs. Safety and pharmacokinetic are assessed.

Official Title
-----------------
A Randomized, Open-label, Single Dose, 2-way Crossover Study to Compare the Pharmacokinetic Characteristics of CKD-395 0.25/750 mg in Healthy Male Volunteers

Conditions
-----------------
Diabetes Mellitus, Type II

Intervention / Treatment
-----------------
* Drug: Duvie Tab. 0.5mg, Glucodaun OR Tab. 750mg
* Drug: CKD-395 0.25/750mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy man older than 19 years at the time of screening. BMI more than 17.5kg/m2 and less than 30.5kg/m2 and weight more than 55kg Subject without congenital or chronic diseases and no psychotic symptoms or findings from the medical examination. Suitable subject who is determined by laboratory tests such as hematology tests,blood chemistry, urinalysis test according to the characteristics of the drug and screening tests such as ECG test. Subject who fully understand the clinical trials after in-depth explanation given prior to the clinical study, decided to join the clinical trials by their will and signed consent form which approved by Chonbuk National University Hospital IRB. Subjects who are able to comply with all scheduled visits, laboratory tests and other procedures. Exclusion Criteria: Subjects who has a history of blood, kidneys, endocrine, respiratory, gastrointestinal, urinary, cardiovascular, hepatic, psychiatric, neurological or allergic diseases that is clinically significant (Except untreated asymptomatic seasonal allergies at the time of administration) Subjects who has a history of gastrointestinal disease or gastrointestinal surgery which can affect drug absorption. Subjects who show AST or AST > 2 times upper limit of normal range. Subjects who drink Alcohol > 210g/week within 6 months prior to the screening. Subjects who take the medication involved in other clinical trials or bioequivalence tests within three months before the first dose medication characters. Subjects who show Systolic Blood Pressure ≥ 140 mmHg or Diastolic Blood Pressure ≥ 90 mmHg at screening. Subjects who have history of alcohol or drug abuse, within 1 year Subjects who treated with metabolizing enzyme inducers or inhibitors such as barbitals within 30days prior to the first dosing. Smoker ( ≥ 20cigarettes/day) Subjects who takes ETC or OTC medicine within 10days before the first IP administration. Subjects who do the whole blood donation within two months or component blood donation within 1month prior to the first dosing. Subjects who can increase risk due to clinical test and administration of drugs or has Severe grade / chronic medical, mental condition or abnormal laboratory result that may interfere with the analysis of test results. Patients with hypersensitivity to lobeglitazone or any other thiazolidinediones ( Rosiglitazone, Rioglitazone) and to Metformin or any other biguanides Patients with severe heart failure or congestive heart failure of needing drug therapy Patients with liver disease Patients with severe renal disease Patients with diabetes mellitus with ketoacidosis, diabetes coma and prior Patients before or after surgery, with severe infections, severe trauma Subjects with hereditary diseases of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Patients with renal disease or renal failure caused by cardiovascular collapse, acute myocardial infarction, sepsis (Serum creatinine ≥ 1.5mg/dL or abnormal creatine clearance) Patients who had a test to injecting radioactive iodine in vein Patients with severe infections or severe traumatic whole body injuries Patients with undernourishment condition or starvation state or hyposthenia or hypopituitarism, or hypoadrenalism Patients with respiratory failure, or stomach disease Subjects who is not able to intake high fat meals Subjects who is not able to comply with guidelines described in the protocol. Subjects who is determined by investigator's decision as unsuitable for clinical trial participation.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RT group<br>R: Reference drug(Duvie Tab. 0.5mg 1T, Glucodaun OR Tab. 750mg 2T) T: Test drug(CKD-395 0.25/750 mg 2T) | Drug: Duvie Tab. 0.5mg, Glucodaun OR Tab. 750mg<br>* oral administration<br>* Other names: Lobeglitazone Sulfate 0.5mg, Metformin HCl 1500mg;Drug: CKD-395 0.25/750mg<br>* oral administration<br>* Other names: Lobeglitazone Sulfate 0.25mg, Metformin HCl 750mg;|
| Experimental: TR group<br>T: Test drug(CKD-395 0.25/750 mg 2T) R: Reference drug(Duvie Tab. 0.5mg 1T, Glucodaun OR Tab. 750mg 2T) | Drug: Duvie Tab. 0.5mg, Glucodaun OR Tab. 750mg<br>* oral administration<br>* Other names: Lobeglitazone Sulfate 0.5mg, Metformin HCl 1500mg;Drug: CKD-395 0.25/750mg<br>* oral administration<br>* Other names: Lobeglitazone Sulfate 0.25mg, Metformin HCl 750mg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast of Lobeglitazone |  | Lobeglitazone: 0(Pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48hrs | 
| AUClast of metformin |  | Metformin: 0(Pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48hrs | 
| Cmax of Lobeglitazone |  | Lobeglitazone: 0(Pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48hrs | 
| Cmax of Lobeglitazone Metformin |  | Metformin: 0(Pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf of Lobeglitazone |  | Lobeglitazone: 0(Pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48hrs | 
| AUCinf of Metformin |  | Metformin: 0(Pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48hrs | 
| Tmax of Lobeglitazone |  | Lobeglitazone: 0(Pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48hrs | 
| Tmax of Metformin |  | Metformin: 0(Pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48hrs | 
| t1/2 of Lobeglitazone |  | Lobeglitazone: 0(Pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48hrs | 
| t1/2 of Metformin |  | Metformin: 0(Pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48hrs | 
| CL/F of Lobeglitazone |  | Lobeglitazone: 0(Pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48hrs | 
| CL/F of Metformin |  | Metformin: 0(Pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48hrs | 
| Vd/F of Lobeglitazone |  | Lobeglitazone: 0(Pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48hrs | 
| Vd/F of Metformin |  | Metformin: 0(Pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48hrs |