Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)
Overview[ - collapse ][ - ]
| Purpose | This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus. |
|---|---|
| Condition | Gestational Diabetes Mellitus |
| Intervention | Drug: Glyburide Drug: Metformin Drug: Glyburide-Metformin combination |
| Phase | Phase 1/Phase 2 |
| Sponsor | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| 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 |
Tracking Information[ + expand ][ + ]
| First Received Date | March 22, 2011 |
|---|---|
| Last Updated Date | October 8, 2013 |
| Start Date | July 2011 |
| Estimated Primary Completion Date | July 2014 |
| Current Primary Outcome Measures | 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. |
| Current Secondary Outcome Measures | 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. |
Descriptive Information[ + expand ][ + ]
| Brief Title | Glyburide and Metformin for Gestational Diabetes Mellitus (GDM) |
|---|---|
| Official Title | Glyburide and Metformin for Gestational Diabetes Mellitus |
| 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 Type | Interventional |
| Study Phase | Phase 1/Phase 2 |
| Study Design | Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | 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. 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. |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 360 |
| Estimated Completion Date | July 2014 |
| Estimated Primary Completion Date | July 2014 |
| Eligibility Criteria | 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. |
| Gender | Female |
| Ages | 18 Years |
| Accepts Healthy Volunteers | Accepts Healthy Volunteers |
| Contacts | Contact: Mary Hebert, PharmD 206-616-5016 mhebert@u.washington.edu |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01329016 |
|---|---|
| Other Study ID Numbers | 820 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| Study Sponsor | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| Collaborators | University of Washington University of Pittsburgh University of Texas Indiana University School of Medicine RTI International |
| Investigators | Principal Investigator: Mary F. Hebert, PharmD, FCCP University of WashingtonPrincipal Investigator: Steve Caritis, MD University of PittsburghPrincipal Investigator: Gary DV Hankins, MD University of TexasPrincipal Investigator: David Flockhart, MD, PhD Indiana University School of Medicine |
| Verification Date | July 2013 |
Locations[ + expand ][ + ]
| Indiana University School of Medicine | Indianapolis, Indiana, United States, 46202 Contact: David Flockhart, MD, PhD | 317-630-8795 | dflockha@iupui.eduPrincipal Investigator: David Flockhart, MD, MS Recruiting |
|---|---|
| University of Pittsburgh | Pittsburgh, Pennsylvania, United States, 15213 Contact: Steve Caritis, MD | 412-641-4874 | scaritis@mail.magee.eduPrincipal Investigator: Steve Caritis, MD Recruiting |
| University of Texas Medical Branch | Galveston, Texas, United States, 77555 Contact: Gary R. Hankins, MD | 409-772-1957 | ghankins@utmb.eduPrincipal Investigator: Gary R. Hankins, MD Recruiting |
| University of Washington | Seattle, Washington, United States, 98195 Contact: Mary F. Hebert, PharmD, FCCP | 206-616-5016 | mhebert@u.washington.eduPrincipal Investigator: Mary F. Hebert, PharmD, FCCP Recruiting |