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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by BC Women's Hospital & Health Centre
Sponsor:
Collaborator:
Bristol-Myers-Squibb/Astra-Zeneca
Information provided by (Responsible Party):
Karen Elkind-Hirsch, BC Women's Hospital & Health Centre
ClinicalTrials.gov Identifier:
NCT02022007
First received: December 17, 2013
Last updated: September 24, 2014
Last verified: September 2014
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Metabolic and Endocrine Effects of Combination of Metformin and DPP4 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 BC Women's Hospital & Health Centre:

Primary Outcome Measures:
  • Fasting and 2 hour glucose levels after glucose load [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Correcting glucose control as evaluated by fasting and 2 hour glucose levels after an OGTT

  • ß-cell compensatory function [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Improving ß-cell compensatory function by enhancing insulin release after an oral glucose load and thus improve or delay a decline in glucose tolerance estimated by the disposition index defined as the product of insulin action (Matsuda index) and insulin secretion (insulinogenic index) derived from the OGTT (SIOGTT x Δinsulin30-0 min to glucose30-0 min).

  • Surrogate measures of insulin sensitivity and secretion [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Improving markers of insulin sensitivity and secretion after an oral glucose load as measured by the Matsuda index and early insulin response adjusted for insulin sensitivity (insulinogenic index/HOMA-IR).


Secondary Outcome Measures:
  • Cardiometabolic risk factors [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    We will further examine whether addition of saxagliptin therapy to metformin is more beneficial than either drug alone in altering the development or progression of select cardiometabolic risk factors as measured by changes in lipids and blood pressure

  • Free androgen index [ Time Frame: Change in baseline to 16 weeks ] [ Designated as safety issue: No ]
    We will further examine whether the administration of combined metformin and saxagliptin therapy is more beneficial than saxagliptin or metformin alone in improving hyperandrogenism as measured by improvements in total testosterone and/or SHBG


Other Outcome Measures:
  • Liver enzymes [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: Yes ]
    SubjeThe safety criteria will include incidence and intensity of adverse events, physical exams, vital signs and laboratory values (liver enzymes).


Estimated Enrollment: 36
Study Start Date: March 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Metformin XR
Metformin 2000 mg 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
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Females 18 years to 42 years of age with PCOS (NIH 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, 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, GLP-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 ßhCG 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

Contacts
Contact: Karen Elkind-Hirsch, Ph.D. 225-231-5278 karen.elkind-hirsch@womans.org
Contact: Martha Paterson, M.D. 225-924-8947

Locations
United States, Louisiana
Woman's Hospital Recruiting
Baton Rouge, Louisiana, United States, 70817
Principal Investigator: Karen Elkind-Hirsch, MSc.,Ph.D.         
Principal Investigator: Martha Paterson, M.D.         
Sub-Investigator: Bobby Webster, M.D.         
Sponsors and Collaborators
BC Women's Hospital & Health Centre
Bristol-Myers-Squibb/Astra-Zeneca
Investigators
Principal Investigator: Karen Elkind-Hirsch, Ph.D. Woman's Hospital, Louisiana
  More Information

No publications provided

Responsible Party: Karen Elkind-Hirsch, Director of Research, BC Women's Hospital & Health Centre
ClinicalTrials.gov Identifier: NCT02022007     History of Changes
Other Study ID Numbers: RP13-013, BMS CV181-354
Study First Received: December 17, 2013
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by BC Women's Hospital & Health Centre:
PCOS
IGT
DPP-4 inhibitor

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

ClinicalTrials.gov processed this record on October 22, 2014