Evaluate the Drug-drugs Interaction Between Lobeglitazone and Empagliflozin

Study Overview
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Brief Summary
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This study is a randomized, open-label, multiple dosing, crossover study to evaluate the drug-drugs interaction between Lobeglitazone and Empagliflozin in healthy male volunteers

Detailed Description
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To healthy male subjects of 30, following treatments are administered dosing in each 3 period(Lobeglitazone or Empagliflozin or Lobe.+Empa.) and wash-out period is a minimum of 7 days. Test Drug 1: Lobeglitazone 0.5mg 1T Test Drug 2: Empagliflozin 25mg 1T Pharmacokinetic blood samples are collected up to 24hrs. Safety, pharmacokinetic and the drug-drugs interaction are assessed.

Official Title
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A Randomized, Open-label, Multiple Dosing, Crossover Study to Evaluate the Drug-drugs Interaction Between Lobeglitazone and Empagliflozin in Healthy Male Volunteers

Conditions
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Diabetes Mellitus, Type II

Intervention / Treatment
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* Drug: Empagliflozin 25mg
* Drug: Lobeglitazone 0.5mg
* Drug: Empagliflozin 25mg/Lobeglitazone 0.5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A healthy person whose age is in between 19 to 45 during the screening tests Whose weight is more than 55 kg, BMI is over 18.5 and under 29.9 during the screening test. (BMI (kg/m2) = weight (kg) / {height (m)}2) A male with no congenital or chronic disease in three years, no history of symptoms in internal treatment, or no knowledge in the area Due to the special characteristics of drugs, the participators must be qualified to do the clinical screening tests The participants must have an ability and willingness to participate throughout the entire trials Exclusion Criteria: A person who has a history of clinically significant cardiovascular, respiratory, liver, kidney, endocrine system, immune system, urinary system diseases, blood-tumor diseases, mental illness. Who had a history of gastrointestinal related disease which can be affected the drug absorption (esophageal achalasia, esophagostenosis, esophageal disease, or Crohn's disease) or surgeries (except a simple appendectomy or herniotomy) Who has a history of hypersensitivity reactions to Empagliflozin or Lobeglitazone or similar series or other excipient ingredients (aspirin, fibrate, antibiotics, etc.) A person whose electrocardiogram value includes QTc > 450 msec, PR interval > 200 msec, QRS duration > 120 msec after screening, or who show clinically significant opinion. Who falls under the following results Liver Function Test (AST, ALT) are exceeded over 1.5x the upper limit of the normal range eGFR < 60mL/min/1.73m2 Who shows the vital sign values of more than 150 mmHg or less than 90 mmHg in systolic pressure or more than 95 mmHg or less than 60 mmHg in diastolic blood pressure Who has history of drug abuses or shows a positive result in the urinary drug screen Who took any prescribed drugs, medicinal plants within the 2 weeks before the first day of dosing or takes any over-the-counter drugs or vitamin supplements within 1 week (but, if other conditions are met, they can still participate in the clinical test through the researcher's judgment) Who took other investigational drugs or bioequivalence drugs within 3 months before the first day of dosing Who participated in whole blood donation within 2 months before the first of dosing, or platelet donations within 1 months. Who received blood a month before the first day of dosing Who constantly drinks alcohol (over 21 units/week, 1 unit = 10 g of pure alcohol) or cannot stop drinking alcohol during the clinical test. Who smokes more than 10 cigarettes per day within 3 months , or who cannot quit smoking when hospitalized Who cannot limit intake of grapefruit or grapefruit containing foods in 48hrs from the first dosing of clinical testing drug to collect pharmacokinetic blood samples Who absorb caffeinated drinks (coffee, tea (black or green tea), soda, coffee flavored milk, energy drinks, etc.) or cannot stop absorbing them 24 hours before hospitalization until discharging Not using a reliable contraception, planning a pregnancy during the study Who has Galactose intolerance, LAPP lactose intolerance, glucose-galactose malabsorption or genetic disorders Person who is not determined unsuitable to participate in this test by the researchers

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Empagliflozin / Lobeglitazone / Empa.+Lobe.<br>Period 1: Empagliflozin 25 mg QD for 5 days Period 2: Lobeglitazone 0.5 mg QD for 5 days Period 3: Empagliflozin 25 mg + Lobeglitazone 0.5 mg QD for 5 days | Drug: Empagliflozin 25mg<br>* Empagliflozin 25 mg QD for 5 days<br>Drug: Lobeglitazone 0.5mg<br>* Lobeglitazone 0.5mg QD for 5 days<br>Drug: Empagliflozin 25mg/Lobeglitazone 0.5mg<br>* Empagliflozin 25 mg + Lobeglitazone 0.5mg QD for 5 days<br>|
| Experimental: Empagliflozin / Empa.+Lobe. / Lobeglitazone<br>Period 1: Empagliflozin 25 mg QD for 5 days Period 2: Empagliflozin 25 mg + Lobeglitazone 0.5 mg QD for 5 days Period 3: Lobeglitazone 0.5 mg QD for 5 days | Drug: Empagliflozin 25mg<br>* Empagliflozin 25 mg QD for 5 days<br>Drug: Lobeglitazone 0.5mg<br>* Lobeglitazone 0.5mg QD for 5 days<br>Drug: Empagliflozin 25mg/Lobeglitazone 0.5mg<br>* Empagliflozin 25 mg + Lobeglitazone 0.5mg QD for 5 days<br>|
| Experimental: Lobeglitazone / Empagliflozin / Empa.+Lobe.<br>Period 1: Lobeglitazone 0.5 mg QD for 5 days Period 2: Empagliflozin 25 mg QD for 5 days Period 3: Empagliflozin 25 mg + Lobeglitazone 0.5 mg QD for 5 days | Drug: Empagliflozin 25mg<br>* Empagliflozin 25 mg QD for 5 days<br>Drug: Lobeglitazone 0.5mg<br>* Lobeglitazone 0.5mg QD for 5 days<br>Drug: Empagliflozin 25mg/Lobeglitazone 0.5mg<br>* Empagliflozin 25 mg + Lobeglitazone 0.5mg QD for 5 days<br>|
| Experimental: Lobeglitazone / Empa.+Lobe. / Empagliflozin<br>Period 1: Lobeglitazone 0.5 mg QD for 5 days Period 2: Empagliflozin 25 mg + Lobeglitazone 0.5 mg QD for 5 days Period 3: Empagliflozin 25 mg QD for 5 days | Drug: Empagliflozin 25mg<br>* Empagliflozin 25 mg QD for 5 days<br>Drug: Lobeglitazone 0.5mg<br>* Lobeglitazone 0.5mg QD for 5 days<br>Drug: Empagliflozin 25mg/Lobeglitazone 0.5mg<br>* Empagliflozin 25 mg + Lobeglitazone 0.5mg QD for 5 days<br>|
| Experimental: Empa.+Lobe. / Empagliflozin / Lobeglitazone<br>Period 1: Empagliflozin 25 mg + Lobeglitazone 0.5 mg QD for 5 days Period 2: Empagliflozin 25 mg QD for 5 days Period 3: Lobeglitazone 0.5 mg QD for 5 days | Drug: Empagliflozin 25mg<br>* Empagliflozin 25 mg QD for 5 days<br>Drug: Lobeglitazone 0.5mg<br>* Lobeglitazone 0.5mg QD for 5 days<br>Drug: Empagliflozin 25mg/Lobeglitazone 0.5mg<br>* Empagliflozin 25 mg + Lobeglitazone 0.5mg QD for 5 days<br>|
| Experimental: Empa.+Lobe. / Lobeglitazone / Empagliflozin<br>Period 1: Empagliflozin 25 mg + Lobeglitazone 0.5 mg QD for 5 days Period 2: Lobeglitazone 0.5 mg QD for 5 days Period 3: Empagliflozin 25 mg QD for 5 days | Drug: Empagliflozin 25mg<br>* Empagliflozin 25 mg QD for 5 days<br>Drug: Lobeglitazone 0.5mg<br>* Lobeglitazone 0.5mg QD for 5 days<br>Drug: Empagliflozin 25mg/Lobeglitazone 0.5mg<br>* Empagliflozin 25 mg + Lobeglitazone 0.5mg QD for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t,ss of Empagliflozin |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| Cmax,ss of Empagliflozin |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| AUC0-t,ss of Lobeglitazone |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| Cmax,ss of Lobeglitazone |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax,ss of Empagliflozin |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| t1/2,ss of Empagliflozin |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| AUCinf of Empagliflozin |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| Tmax,ss of Lobeglitazone |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| t1/2,ss of Lobeglitazone |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours | 
| AUCinf of Lobeglitazone |  | Day 1, 2, 3, 4 (Day 12 - 15, Day 23 - 26): 0 hour, Day 5 (Day 16, Day 27): 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 hours |