Drug-drug Interaction Study(Lobeglitazone, Warfarin)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate a pharmacokinetic drug interaction between lobeglitazone and warfarin in healthy subjects.

Detailed Description
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From day 1 to day 12, lobeglitazone 0.5mg is administered daily to Group 1 subjects during period 1. Then on day 5,warfarin 25mg is co-administered Group 1 subjects at period 1. After 10 day-break, warfarin 25mg is administered Group 1 subjects at period 2. On period 2, lobeglitazone is not administered. Group 2 is administered in reverse order.

Official Title
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Open Label, Randomized, Crossover Study to Evaluate a Pharmacokinetic Drug Interaction Between Lobeglitazone and Warfarin in Healthy Subjects

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Lobeglitazone
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A healthy male volunteer between 19 and 55 years old. BMI between 19 and 27. Signed the informed consent form prior to study participation. Able to participate in the entire trial Exclusion Criteria: Clinically significant hepatic, renal, digestive system, respiratory system, endocrine system, nervous system, hematologic, cardiovascular system, tumor or have history of tumor Clinically significant hemorrhagic disease Genetic problems such as galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Have hypersensitivity reactions history for lobeglitazone, warfarin, excipient of IP or aspirin, antibiotics Medication which might significantly alter the absorption, distribution, metabolism, or excretion of investigational products within 30 days prior to screening Participated in the other clinical trials and administrated IP within 60 days prior to screening Subject takes ethical drug or herbal medicine within 14 days, OTC within 7 days before screening Previously donate whole blood within 60 days or component blood within 30 days sit SBP < 90mmHg or sit SBP ≥ 140mmHg or sit DBP < 60mmHg or sit DBP ≥ 90mmHg A heavy alcohol consumer (alcohol > 140 g/week) or cannot stop drinking A heavy smoker (cigarette > 10 cigarettes per day) or cannot stop smoking A heavy caffeine consumer (more than 4cups per a day) or A heavy grapefruit consumer (more than 1cup per a day) or cannot stop having Positive for the Triage TOX drug on urine Positive for HIV antibody, HBsAg, HCV antibody test AST, ALT or Total bilirubin > UNL * 1.5 Estimated GFR < normal limit INR, aPTT over the normal limit Clinically significant laboratory test result Clinically significant ECG An impossible one who participates in clinical trial by investigator's decision including other reason

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 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: Lobeglitazone<br>Subjects received Lobeglitazone 0.5 mg daily for 12 days in one period and in the other period, Subjects don't receive Lobeglitazone. | Drug: Lobeglitazone<br> <br> |
| Experimental: Warfarin<br>Subjects received Warfarin 25 mg once at period 1 and 2. | Drug: Warfarin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess AUC of lobeglitazone |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h | 
| Assess Cmax of lobeglitazone |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h | 
| Assess AUC of S-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess Cmax of S-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess AUC of R-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess Cmax of R-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess tmax of lobeglitazone |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h | 
| Assess t1/2 of lobeglitazone |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h | 
| Assess CL/F of lobeglitazone |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h | 
| Assess Vd/F of lobeglitazone |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h | 
| Assess tmax of S-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess t1/2 of S-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess CL/F of S-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess Vd/F of S-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess tmax of R-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess t1/2 of R-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess CL/F of R-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 
| Assess Vd/F of R-warfarin |  | 0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lobeglitazone, Warfarin, Type 2 Diabetes Mellitus, Drug-Drug interaction, Phase 1