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Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborators:
University of Washington
University of Pittsburgh
University of Texas
Indiana University School of Medicine
RTI International
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01329016
First received: March 22, 2011
Last updated: October 8, 2013
Last verified: July 2013

March 22, 2011
October 8, 2013
July 2011
July 2014   (final data collection date for primary outcome measure)
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.
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 pregancy 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.
Complete list of historical versions of study NCT01329016 on ClinicalTrials.gov Archive Site
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.
Same as current
Not Provided
Not Provided
 
Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)
Glyburide and Metformin for Gestational Diabetes Mellitus

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

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Gestational Diabetes Mellitus
  • 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.
  • 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.
  • Active Comparator: GDM Subjects
    Women with GDM requiring treatment
    Interventions:
    • Drug: Glyburide
    • Drug: Metformin
    • Drug: Glyburide-Metformin combination
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
360
July 2014
July 2014   (final data collection date for primary outcome measure)

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.
Female
18 Years to 45 Years
Yes
Contact: Mary Hebert, PharmD 206-616-5016 mhebert@u.washington.edu
Contact: Linda M Brown, MPH, DrPH 301-816-4626 lindabrown@rti.org
United States
 
NCT01329016
820
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • University of Washington
  • University of Pittsburgh
  • University of Texas
  • Indiana University School of Medicine
  • RTI International
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
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP