A Clinical Trial for Analysis of Intestinal Microbiome Affecting PK, PD, and Safety of Metformin

Study Overview
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Brief Summary
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This clinical trial is intended to evaluate the effects of the changes in intestinal microbiome by antibiotics (PO vancomycin) on the pharmacokinetic /pharmacodynamic and safety profiles of metformin in healthy male volunteers.

Official Title
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A Clinical Trial for Analysis of Intestinal Microbiome Affecting Pharmacokinetics, Pharmacodynamics, and Safety of Metformin in Healthy Volunteers

Conditions
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Human Microbiome

Intervention / Treatment
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* Drug: Metformin (part 1)
* Drug: Vancomycin
* Drug: Metformin (part 2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 19 to 45, healthy male subjects(at screening) Body weight between 50.0 kg - 100.0 kg, BMI between 18.0 - 28.0 kg/m2 Subject who totally understand the progress of this clinical trials, make decision by his free will, and signed a consent form to follow the progress. Exclusion Criteria: Subject who has a past or present history of any diseases following below.(liver, kidney, neurology, immunology, pulmonary, endocrine, hematology, oncology, cardiology, mental disorder) Subject who had GI tract disease(Crohn's disease, ulcer, acute or chronic pancreatitis) or surgery (appendectomy, hernioplasty are excluded) Serum AST(SGOT), ALT(SGPT)>1.5 times upper limit of normal range MDRD eGFR <80mL/min/1.73m2 Subject who had drug (Aspirin, antibiotics) hypersensitivity reaction Subject who already participated in other trials in 3 months Subject who had whole blood donation in 2 months, or component blood donation in 1 month or transfusion in 1 month currently.

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: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Metformin/Vancomycin | Drug: Metformin (part 1)<br>* 1 4d: Metformin 1000 mg bid (Except for 500 mg after 1d lunch), 16d 19d: Metformin 1000 mg bid (Except for 500 mg after 16d lunch).<br>* Other names: Diabex Tab., 500 mg;Drug: Vancomycin<br>* 11d: Vancomycin 250 mg bid, 12 17d: Vancomycin 500 mg bid<br>* Other names: Vancozin cap., 250 mg;|
| Experimental: Part 2<br>Metformin | Drug: Metformin (part 2)<br>* 1 4d: Metformin 1000 mg bid (Except for 500 mg after 1d lunch)<br>* Other names: Diabex Tab., 500 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the gut microbiome species change | Compare how the gut microbiome species change after metformin (or vancomycin) multiple dosing | Day 1/4/16/19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the maximum plasma concentration (Cmax) of metformin | Compare the maximum plasma concentration (Cmax) of metformin before and after vancomycin PO treatment | Day 4/19 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post-dose) | 
| Compare the area under the plasma concentration versus time curve (AUC) of metformin | Compare the area under the plasma concentration versus time curve (AUC) of metformin before and after vancomycin PO treatment | Day 4/19 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post-dose) | 
| Compare the maximum blood glucose concentration (Gmax) | Oral glucose tolerance test (OGTT); Compare the maximum blood glucose concentration (Gmax) before and after metformin (or vancomycin) PO treatment | Day 1/4/16/19 (pre-dose (75 g glucose), 0.25, 0.5, 0.75, 1, 1.5. 2 hours) | 
| Compare the area under the blood glucose concentration versus time curve (AUC) | Oral glucose tolerance test (OGTT); Compare the area under the blood glucose concentration versus time curve (AUC) before and after metformin (or vancomycin) PO treatment | Day 1/4/16/19 (pre-dose (75 g glucose), 0.25, 0.5, 0.75, 1, 1.5. 2 hours) |