Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)

Gestational Diabetes Mellitus Clinical Trial

— GDM  

Official title:

Glyburide and Metformin for Gestational Diabetes Mellitus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01329016
• Other study ID #: 820
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: March 22, 2011
• Last updated: February 9, 2015
• Start date: July 2011
• Est. completion date: June 2015

Study information

• Verified date: February 2015
• Source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: June 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes Mellitus

Intervention

Drug:
• Glyburide
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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Texas Medical Branch	Galveston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Washington	Seattle	Washington

Sponsors (6)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Indiana University School of Medicine, RTI International, University of Pittsburgh, University of Texas, University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study drug dosage in pregnancy	(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.	Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs)	Yes
Secondary	Determine GLY and MET PK parameters	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.	Conclusion of data collection (up to 6 months)	Yes