Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)

Phase 1

• Conditions: Gestational Diabetes Mellitus
• Interventions: Drug: Glyburide; Drug: Metformin; Drug: Glyburide-Metformin combination

• Registration Number: NCT01329016
• Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Brief Summary

This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2011-03-22
• Study First Submitted QC: 2011-04-04
• Study First Posted: 2011-04-05
• Study Start: 2011-07
• Status Verified: 2015-02
• Last Update Submitted: 2015-02-09
• Last Update Posted: 2015-02-10
• Primary Completion: 2015-05
• Study Completion: 2015-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 360

Inclusion Criteria

Gestational Diabetes Subject Selection

1. Pregnant women (singleton pregnancy)

2. Gestational diabetes mellitus

3. Able to give written informed consent

4. Drug treatment is required for GDM

5. Gestational age 20-32 weeks

   • Gestational diabetes diagnosis must occur after 20 weeks and prior to 32 weeks gestation
   • Randomization and treatment initiation must occur no later than 32 weeks gestation

6. Willing to avoid ethanol

7. 18-45 years of age

Type 2 Diabetes Mellitus Subject Selection

1. Able to give written informed consent
2. New diagnosis of type 2 diabetes mellitus
3. Plan to receive metformin for treatment of type 2 diabetes mellitus
4. 18-45 years of age
5. Female
6. Negative pregnancy test
7. Hemoglobin A1C > 7%

Healthy Pregnant Women

1. Able to give written informed consent
2. Pregnant women (singleton)
3. Normal 1-hour glucose tolerance test
4. 20-32 weeks gestation
5. 18-45 years of age

Neonates: All the infants of the pregnant women participating in this study will be included

Exclusion Criteria

Women with GDM and T2DM

1. Women taking medications expected to interact with glyburide, metformin or alter blood glucose concentrations
2. Serum creatinine > 1.2 mg/dL
3. Hematocrit < 28%
4. Allergy to glyburide, metformin or sulfa
5. Significant hepatic disease
6. Congestive heart failure or history of MI
7. Moderate to severe pulmonary disease
8. Adrenal or pituitary insufficiency

Healthy Pregnant Women

1. Receiving any hypoglycemic agents
2. Receiving corticosteroids
3. Known kidney, liver, heart, pulmonary, adrenal or pituitary disease
4. Hematocrit < 28%

Neonates

1. Infants that are not viable or too ill for blood sample collection will be included for clinical outcomes data collection, but will be excluded from other research activities.
2. Infants < 1.5 kg will be included for clinical outcomes data collection, but will be excluded from blood sample collection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GDM Subjects	Glyburide-Metformin combination	Women with GDM requiring treatment
GDM Subjects	Glyburide	Women with GDM requiring treatment
GDM Subjects	Metformin	Women with GDM requiring treatment

Primary Outcome Measures

Name	Time	Method
Study drug dosage in pregnancy	Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs)	(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.

Secondary Outcome Measures

Name	Time	Method
Determine GLY and MET PK parameters	Conclusion of data collection (up to 6 months)	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.

Trial Locations

Locations (4)

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Texas Medical Branch; 🇺🇸 Galveston, Texas, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States