Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)
This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus.
Gestational Diabetes Mellitus
Drug: Glyburide-Metformin combination
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Glyburide and Metformin for Gestational Diabetes Mellitus|
- Study drug dosage in pregnancy [ Time Frame: Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs) ] [ Designated as safety issue: Yes ](1) Determination of metformin dosage in pregnancy needed to produce comparable concentrations to the approved dosage range in non-pregnant women. (2)To compare metformin apparent oral clearance in pregnant and non-pregnant women. (3)To evaluate the effect of GLY monotherapy, MET monotherapy, and GLY-MET combination on insulin sensitivity, beta-cell responsivity index and disposition index (response vectors) describing the mechanism and magnitude of effect.
- Determine GLY and MET PK parameters [ Time Frame: Conclusion of data collection (up to 6 months) ] [ Designated as safety issue: Yes ]Determining GLY & MET PK parameters, including AUC, max concentration, time to max & min concentrations, oral clearance, half-life, oral volume of distribution, umbilical cord plasma concentrations; correlation between CYP2C9, CYP3A5, BCRP, OATP2B1 genotypes & GLY PK/PD; GLY & MET PD parameters, including derived parameters from PK/PD modeling for pregnant & nonpregnant subjects; duration of initiation of treatment to glycemic control; effects of GDM & glycemic control on maternal & umbilical cord EPC cells & sFLT concentrations; GLY & MET half-life in neonates; efficacy & safety data.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Active Comparator: GDM Subjects
Women with GDM requiring treatment
Women with GDM who require treatment will be given glyburide 2.5 mg. Medication will be given at least twice daily and equal doses will be given for each dosing time for the 3 days prior to the pharmacokinetic study day.Drug: Metformin
Women with GDM requiring treatment will be given metformin 500 mg. Medication will be administered at least twice daily and equal doses will be given for each dosing time for the 3 days prior to the pharmacokinetic study day.Drug: Glyburide-Metformin combination
Women with GDM requiring treatment will be given glyburide 2.5 mg with metformin 500 mg. Medications will be administered at least twice daily and equal doses will be given for each dosing time 3 days prior to the pharmacokinetic study day.
No Intervention: Non-pregnant Type 2 Diabetes Milletus Subjects
Non-pregnant women with Type 2 diabetes mellitus who plan to use metformin treatment
No Intervention: Healthy Pregnant Women
Healthy pregnant women with normal 1-hour glucose tolerance test
Gestational diabetes mellitus (GDM) is a common complication of pregnancy. Multiple treatment regimens are currently used for the management of GDM. Following failure of diet therapy, insulin, glyburide and metformin are all used in the treatment of GDM with the oral medications providing comparable outcomes with insulin but easier route of administration and schedule. The proposed work will evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of glyburide and metformin alone and in combination in order to lay the foundation in establishing dosage and response information that could be utilized in designing a phase III randomized trial that will ultimately evaluate GDM treatment optimization.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01329016
|United States, Indiana|
|Indiana University School of Medicine|
|Indianapolis, Indiana, United States, 46202|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|University of Texas Medical Branch|
|Galveston, Texas, United States, 77555|
|United States, Washington|
|University of Washington|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Mary F. Hebert, PharmD, FCCP||University of Washington|
|Principal Investigator:||Steve Caritis, MD||University of Pittsburgh|
|Principal Investigator:||Gary DV Hankins, MD||University of Texas|
|Principal Investigator:||David Flockhart, MD, PhD||Indiana University School of Medicine|