Efficacy and Safety of CKD-501 Added to D150 Plus D745 25mg Therapy in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to prove that the group treated with CKD-501 in combination added that the reduction of glycated hemoglobin superior to placebo treated group added in combination.

Detailed Description
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The aim of this phase III study was to evaluate the efficacy and safety of additional combined CKD-501 administration for 24 weeks in patients with type 2 diabetes who were not adequately controlled for blood glucose by the combination of D150 and D745 25mg . Furthermore, the extension study for additional 28 weeks is designed to confirm long term safety of actual drug as an oral hypoglycemic agent.

Official Title
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Efficacy and Safety of CKD-501 Added to D150 Plus D745 25mg Therapy in Patients With Type 2 Diabetes Inadequately Controlled With D150 Plus D745 25mg: Multi-center, Randomized, Double-blind, Parallel-group, Placebo Control, Therapeutic Confirmatory Study.

Conditions
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Type2 Diabetes

Intervention / Treatment
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* Drug: CKD-501 0.5mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 19 years and 75 years old(male or female) Type Ⅱ diabetes mellitus The patient who has been taking oral hypoglycemic agent at least 8weeks with HbA1c 7 to 10% at screening test Body Mass Index between 21kg/㎡ and 40kg/㎡ C-peptide > 1.0 ng/ml Agreement with written informed consent HbA1c 7 to 10% after Run-in period Exclusion Criteria: Type I diabetes or secondary diabetes Continuous or non continuous treatment(over 7 days) insulin within 3 months prior to screening Treatment with Thiazolidinedione within 3months or patient who has experience such as hypersensitivity reaction, serious adverse event with Thiazolidinedione(TZD), sodium glucose cotransporter 2(SGLT2) inhibitor, Biguanide. Chronic(continuous over 7 days) oral or non oral corticosteroids treatment within 1 month prior to screening Treatment with anti-obesity drugs within 3months Past history: lactic acidosis, genetic problem such as galactose intolerance, etc. Acute or chronic metabolic acidosis including diabetic ketoacidosis History of proliferative diabetic retinopathy Patient with severe infection, severe injury Patients with urinary tract infection including urinary tract sepsis and pyelonephritis Malnutrition, weakness, starvation, hyposthenia, pituitary insufficiency or adrenal insufficiency History of malignant tumor within 5years Drug abuse or history of alcoholism Severe pulmonary dysfunction Severe GI disorder History of myocardial infarction, heart failure, cerebral infarction, cerebral hemorrhage or unstable angina within 6 months Abnormal lab result: ① Fasting Plasma Glucose > 270 mg/dl ② Triglyceride ≥ 500 mg/dl ③ Significant liver dysfunction or AST(Aspartate transaminase)/ALT(Alanine transaminase) ≥ normal range*3 or Total bilirubin ≥ normal range*2 ④ Hemoglobin<10.5g/dL ⑤ Abnormality of thyroid function(significantly out of normal TSH(Thyroid Stimulating Hormone) range) eGFR(Estimated glomerular filtration rate) is less than 60ml/min/1.73m^2 Pregnant women or nursing mothers Fertile women who not practice contraception with appropriate methods Participated in other trial within 4 weeks or participating in other trial at present In investigator's judgment

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CKD-501 0.5mg<br>CKD-501 0.5mg | Drug: CKD-501 0.5mg<br>* CKD-501 0.5mg, orally, 1 tablet once a day for 24weeks or 52weeks(if extension study) with D150 and D745<br>* Other names: Lobeglitazone 0.5mg;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo, orally, 1 tablet once a day for 24weeks with D150 and D745. CKD-501 placebo will be changed to CKD-501 from extension stydy to EOS(end of study).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Glycosylated Hemoglobin (HbA1c) |  | Baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Glycosylated Hemoglobin (HbA1c) |  | Baseline, 52 weeks | 
| Change from baseline in Fasting plasma glucose |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in HOMA-IR(Homeostasis Model Assessment of Insulin Resistance) |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in HOMA-β(Homeostasis Model Assessment of β-cell function) |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in QUICKI(Quantitative Insulin Check Index) |  | Baseline, 24 weeks, 52 weeks | 
| HbA1c target achievement rate at 24 weeks(HbA1c < 6.5%, 7%) |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in Total Cholesterol |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in Triglycerides |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in LDL-Cholesterol |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in HDL-Cholesterol |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in non-HDL-Cholesterol |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in Small Dense LDL-Cholesterol |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in FFA(Free Fatty Acid) |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in Apo-AⅠ |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in Apo-B |  | Baseline, 24 weeks, 52 weeks | 
| Change from baseline in Apo-CⅢ |  | Baseline, 24 weeks, 52 weeks | 
| Evaluate safety of CKD-501 from number of participants with adverse events |  | Baseline, 24 weeks, 52 weeks |