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

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

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.

Study Overview

• Status: Completed
• Conditions: Human Microbiome
• Intervention / Treatment: Drug: Metformin (part 1); Drug: Vancomycin; Drug: Metformin (part 2)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 03080
      • SNUBH Clinical trial centor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1; Metformin/Vancomycin	Drug: Metformin (part 1); 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).; Other Names: Diabex Tab., 500 mg; Drug: Vancomycin; 11d: Vancomycin 250 mg bid, 12~17d: Vancomycin 500 mg bid; Other Names: Vancozin cap., 250 mg
EXPERIMENTAL: Part 2; Metformin	Drug: Metformin (part 2); 1~4d: Metformin 1000 mg bid (Except for 500 mg after 1d lunch); Other Names: Diabex Tab., 500 mg

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2018
• Primary Completion (ACTUAL): February 28, 2019
• Study Completion (ACTUAL): February 28, 2019

Study Registration Dates

• First Submitted: January 8, 2019
• First Submitted That Met QC Criteria: January 16, 2019
• First Posted (ACTUAL): January 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Metformin
• Other Study ID Numbers: MMP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No