This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Saxagliptin + Metformin Compared to Saxagliptin or Metformin Monotherapy in PCOS Women With Impaired Glucose Homeostasis (BMS-AZPCOS)

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Karen Elkind-Hirsch, Woman's
ClinicalTrials.gov Identifier:
NCT02022007
First received: December 17, 2013
Last updated: May 25, 2017
Last verified: May 2017
  Purpose
The objective of the present proposal is to compare the clinical, endocrine and metabolic effects of therapy with combination saxagliptin and metformin to saxagliptin and metformin monotherapy in women with PCOS and prediabetic hyperglycemia (IFG, IGT or IFG/IGT). Saxagliptin is an oral dipeptidyl peptidase IV (DPP-4) inhibitor whose mechanism of action is to prolong the duration of blood glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels by inhibiting their degradation and thereby augmenting insulin secretion. This study will serve as a pilot investigation to open perspectives for future studies to explore the potential of combining anti-diabetic drugs with different mechanisms of action in in patients with PCOS and impaired glucose regulation (IGR), especially ones for whom standard treatment with metformin is less effective.

Condition Intervention Phase
Polycystic Ovary Syndrome Disorder of Glucose Regulation Drug: Metformin XR Drug: Saxagliptin Drug: Saxagliptin-Metformin XR Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Karen Elkind-Hirsch, Woman's:

Primary Outcome Measures:
  • 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


Secondary Outcome 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.


Other Outcome Measures:
  • 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


Enrollment: 38
Study Start Date: March 2014
Study Completion Date: October 2016
Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Other Names:
  • Glucophage XR
  • Biguanide-insulin sensitizer
Active Comparator: Saxagliptin
Saxagliptin 5 mg QD for 16 weeks
Drug: Saxagliptin

Start 1 pill (5 mg)) for 3 weeks

Remain at 1 pill (5mg dose) for remainder of study

Other Names:
  • Onglyza
  • DPP-4 inhibitor
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

Other Names:
  • Kombiglyze XR
  • Combination DPP-4 inhibitor and Glucophage XR

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Females 18 years to 42 years of age with polycystic ovary syndrome(NIH PCOS criteria) with prediabetic hyperglycemia determined by an 75 gram oral glucose tolerance test (OGTT). Study subjects will be inclusive of PCOS women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT).
  • Written consent for participation in the study

Exclusion Criteria:

  • Presence of significant systemic disease, heart problems including congestive heart failure, history of pancreatitis, or diabetes mellitus (Type 1 or 2)
  • Any hepatic diseases in the past (viral hepatitis, toxic hepatic damage, jaundice of unknown etiology), gallstones, abnormal liver function tests or renal impairment (elevated serum creatinine levels or abnormal creatinine clearance)
  • Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia
  • Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %)
  • Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)
  • Use of hormonal medications, drugs known to affect gastrointestinal motility, lipid-lowering (statins, etc.) and/or anti-obesity drugs or medications that interfere with carbohydrate metabolism (such as isotretinoin, hormonal contraceptives, gonadotropin releasing hormone (GnRH) analogues, glucocorticoids, anabolic steroids, C-19 progestins) for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) for at least 4 weeks
  • Prior history of a malignant disease requiring chemotherapy
  • Known hypersensitivity or contraindications to use of insulin sensitizers such as metformin or thiazolidinediones
  • History of hypersensitivity reaction to saxagliptin or other DPP-4 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions)
  • Current use of metformin, thiazolidinediones, glucagon-like peptide -1 receptor agonists, DPP-4 inhibitors, or weight loss medications (prescription or OTC) Patients must stop use of insulin sensitizers or antidiabetic medicines such as metformin for at least 4 weeks or thiazolidinediones, GLP1 agonists or DPPIV inhibitors for 8 weeks.
  • Prior use of medication to treat diabetes except gestational diabetes
  • Use of drugs known to exacerbate glucose tolerance
  • Eating disorders (anorexia, bulimia) or gastrointestinal disorders
  • Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy during the study treatment interval, breastfeeding, or known pregnancy in last 2 months
  • Active or prior history of substance abuse (smoke or tobacco use within past 3 years) or significant intake of alcohol or history of alcoholism
  • Patient not willing to use adequate barrier contraception during study period (unless sterilized or have an IUD).
  • Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables
  • Inability or refusal to comply with protocol
  • Not currently participating or having participated in an experimental drug study in previous three months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02022007

Locations
United States, Louisiana
Woman's Hospital
Baton Rouge, Louisiana, United States, 70817
Sponsors and Collaborators
Woman's
AstraZeneca
Investigators
Principal Investigator: Karen Elkind-Hirsch, Ph.D. Woman's Hospital, Louisiana
  More Information

Responsible Party: Karen Elkind-Hirsch, Director of Research, Woman's
ClinicalTrials.gov Identifier: NCT02022007     History of Changes
Other Study ID Numbers: RP13-013
BMS CV181-354 ( Other Grant/Funding Number: Bristol Myers Squibb/Astra Zaneca )
Study First Received: December 17, 2013
Results First Received: November 9, 2016
Last Updated: May 25, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Karen Elkind-Hirsch, Woman's:
PCOS
IGT
DPP-4 inhibitor

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Saxagliptin
Metformin
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2017