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

• Metformin (part 1) (Drug), also known as Diabex Tab., 500 mg: 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).
• Vancomycin (Drug), also known as Vancozin cap., 250 mg: 11d: Vancomycin 250 mg bid, 12\~17d: Vancomycin 500 mg bid
• Metformin (part 2) (Drug), also known as Diabex Tab., 500 mg: 1\~4d: Metformin 1000 mg bid (Except for 500 mg after 1d lunch)

Primary outcomes

• Compare the gut microbiome species change [Day 1/4/16/19]: Compare how the gut microbiome species change after metformin (or vancomycin) multiple dosing

Secondary outcomes

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

Sex: Male, ages: 19 Years to 45 Years, accepts healthy volunteers

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.

• Results publication: Kim E, Kim AH, Lee Y, Ji SC, Cho JY, Yu KS, Chung JY. Effects of vancomycin-induced gut microbiome alteration on the pharmacodynamics of metformin in healthy male subjects. Clin Transl Sci. 2021 Sep;14(5):1955-1966. doi: 10.1111/cts.13051. Epub 2021 May 31. PMID 33982376

• Jae-Yong Chung, Principal investigator, Seoul National University Bundang Hospital