Saxagliptin + Metformin Compared to Saxagliptin or Metformin Monotherapy in PCOS Women With Impaired Glucose Homeostasis (BMS-AZPCOS)
|Polycystic Ovary Syndrome Disorder of Glucose Regulation||Drug: Metformin XR Drug: Saxagliptin Drug: Saxagliptin-Metformin XR||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
|Official Title:||Metabolic and Endocrine Effects of Combination of Metformin and DPP-4 Inhibitor Saxagliptin Compared to Saxagliptin or Metformin XR Monotherapy in Patients With PCOS and Impaired Glucose Regulation: A Single-blinded Randomized Pilot Study|
- Glucose Metabolism [ Time Frame: 16 weeks ]Glucose metabolic secretory status after drug treatment (normal, impaired or diabetic). We used the American Diabetes Association (ADA) definition of impairment which is fasting glucose greater than 100 mg/dL and/or 2 hour glucose greater than 140 mg/dL.
- Oral Disposition Index [ Time Frame: 16 weeks ]Post-treatment in insulin-sensitivity-secretion index . The insulin secretion-sensitivity index (IS-SI) provides an estimate of β-cell compensation relative to the prevailing insulin resistance, not absolute insulin secretion. It is derived by applying the concept of the disposition index (DI) to measurements obtained during the 2-h OGTT. The IS-SI, a surrogate measure of the DI derived from the OGTT (IGI multiplied by the SIOGTT], was calculated as the product of acute β-cell response [IGI] and Matsuda index (SIOGTT) based on the existence of the predicted hyperbolic relationship between these two measures
- Fasting Glucose [ Time Frame: 16 weeks ]Post-treatment fasting glucose levels
- Mean Blood Glucose During the OGTT [ Time Frame: 16 weeks ]Post-treatment mean blood glucose levels. Mean blood glucose (MBG) concentrations were calculated by summing glucose values obtained at 0,30,60 and 120 minutes during the OGTT and dividing by 4.
- Matsuda Index of Insulin-Sensitivity (SI OGTT) [ Time Frame: 16 weeks ]Post-treatment insulin sensitivity index. The Matsuda index of whole-body insulin sensitivity is calculated from an oral glucose tolerance test (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), and is highly correlated with the rate of whole-body glucose disposal during the euglycemic insulin clamp
- Pancreatic ß-cell Compensatory Function [ Time Frame: 16 weeks ]Post-treatment corrected early phase insulin secretion index (IGI/HOMA-IR). . Early pancreatic β-cell response is estimated as the insulinogenic index (IGI) derived from the ratio of the increment of insulin to that of glucose 30 minutes after a glucose load (insulin 30 min − insulin 0 min/glucose 30 min − glucose 0 min) corrected for by the relative level of insulin resistance (IGI/HOMA-IR which is estimated by homeostasis model assessment of insulin resistance using fasting insulin and glucose levels).
- Body Mass Index at 16 Weeks [ Time Frame: 16 weeks ]Height and weight measurements were used to calculate body mass index (BMI), defined as kg/m2.
- Waist Circumference at 16 Weeks [ Time Frame: 16 weeks ]The circumference measurement was taken in the upright position using a 15-mm width flexible metric tape held close to the body but not tight enough to indent the skin. Waist circumference (WC) was measured in centimeters at the narrowest level midway between the lowest ribs and the iliac crest.
- Menstrual Cycle Interval at 16 Weeks [ Time Frame: 16 weeks ]The number of menstrual cycles during the previous year was recorded and the average menstrual interval calculated by dividing 365 by the number of menstrual cycles in the previous year . During the study period, the patients in a menstrual diary recorded vaginal bleeding over 16 weeks. The effects of treatment intervention on menstrual cycle interval was calculated evaluated by dividing 112 days by the number of menstrual cycles recorded in each patient's menstrual cycle diary.
- Triglyceride (TRG) /HDL-cholesterol Ratio [ Time Frame: 16 weeks ]The measure of TRG levels and HDL- cholesterol levels are used as an estimate of insulin sensitivity. A TRG/HDL-C ratio of greater than 3.0 is used as an indirect measure of insulin resistance
- Free Androgen Index (FAI) [ Time Frame: 16 weeks ]Hyperandrogenism is measured by a combination of total testosterone (T) and sex hormone binding globulin (SHBG). The FAI was calculated as the quotient 100 x T/SHBG; hyperandrogenism was defined by a FAI value >3.85.
- Number of Participants With No Clinically Significant Changes in Liver Enzyme Levels or Positive Pregnancy Tests [ Time Frame: 16 weeks ]The safety criteria will include laboratory values for liver enzymes and document the absence of pregnancy in all participants during the trial
|Study Start Date:||March 2014|
|Study Completion Date:||October 2016|
|Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Metformin XR
Metformin 2000 mg daily (QD) for 16 weeks
Drug: Metformin XR
Start 2 pills (2 pills of 500 mg =1000mg XR) for 3 weeks
Increase to 4 pills as tolerated (4 pills of 500 mg XR =2000 mg XR) for remainder of study
Active Comparator: Saxagliptin
Saxagliptin 5 mg QD for 16 weeks
Start 1 pill (5 mg)) for 3 weeks
Remain at 1 pill (5mg dose) for remainder of study
Experimental: Saxagliptin-Metformin XR
Saxagliptin-Metformin XR (combination pill)
5mg Saxagliptin/2000 mg Metformin XR QD for 16 weeks
Drug: Saxagliptin-Metformin XR
Start 1 pill (2.5 mg/ 1000mg XR) for 3 weeks
Increase to 2 pills as tolerated (5mg/2000 mg XR) for remainder of study
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT02022007
|United States, Louisiana|
|Baton Rouge, Louisiana, United States, 70817|
|Principal Investigator:||Karen Elkind-Hirsch, Ph.D.||Woman's Hospital, Louisiana|