EQW, DAPA, EQW/DAPA, DAPA/MET ER and PHEN/TPM ER in Obese Women With PolycysticOvary Syndrome (PCOS)

• Status: Completed
• Trial end date: 2020-10-09
• Target enrollment: 0
• Participant gender: Female

Summary

This is a randomized, single-blind, parallel 5 treatment group 24-week trial designed to directly compare the therapeutic effects of exenatide once weekly (EQW), dapagliflozin (DAPA), EQW plus DAPA, combined DAPA/metformin extended release (XR) and the weight loss medication, phentermine/topiramate extended release (PHEN/TPM ER) on metabolic and endocrinological parameters in overweight/obese non-diabetic women with PCOS. In this study, we will examine the efficacy of these therapies on metabolic parameters, body weight and body composition, anthropometric measurements, and reproductive function in a well-defined group of pre-menopausal overweight/obese, non-diabetic women with PCOS, focusing on their relationship to insulin resistance and obesity. We hope to determine which treatment(s) addressing the multifaceted disturbances of individual subgroups emerge as the preferable therapy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Woman's
• Collaborator: AstraZeneca
• Treatments: Dapagliflozin; Exenatide; Glucagon; Glucagon-Like Peptide 1; Metformin; Phentermine; Sodium-Glucose Transporter 2 Inhibitors; Topiramate

Criteria

Inclusion Criteria:

1. Non-diabetic women (18-45 years)

2. PCOS- NIH criteria hyperandrogenism and irregular menses

3. Obese class I, II, and III (BMI >30<45)

4. Willing to use effective contraception consistently during therapy which is defined as:

1. an intrauterine device, tubal sterilization, or male partner vasectomy, or

2. combination of two barrier methods with one being male condom.

5. Written consent for participation in the study

Exclusion Criteria:

1. Presence of significant systemic disease, heart problems including congestive heart failure, unstable angina or acute myocardial infarction, current infectious liver disease, acute stroke or transient ischemic attacks, history of pancreatitis, or diabetes mellitus (Type 1 or 2)

2. Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or significant abnormal liver function tests defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN

3. Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease. Patients with a history of nephrolithiasis are also excluded due to increased association with kidney stone formation.

4. Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia

5. Significantly elevated triglyceride levels (fasting triglyceride > 400 mg/dL)

6. Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)

7. Use of hormonal medications, lipid-lowering (statins, etc.), anti-obesity drugs or weight loss medications (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, hormonal contraceptives, gonadotropin-releasing hormone agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) stopped for at least 4 weeks

8. Prior history of a malignant disease requiring chemotherapy

9. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status

10. History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.

11. Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions

12. Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide)

13. Use of metformin, thiazolidinediones, GLP-1 receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, SGLT2 inhibitors stopped for at least 4 weeks.

14. Prior use of medication to treat diabetes except gestational diabetes

15. Eating disorders (anorexia, bulimia) or gastrointestinal disorders

16. Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months

17. Active or prior history of substance abuse (smoke or tobacco use within past 3 years) or significant intake of alcohol

18. Having a history of bariatric surgery

19. Patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD)

20. Patients with glaucoma or history of increased intraocular pressure, or use of any medications to treat increased intraocular pressure

21. Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables. Patients with a history of bipolar disorder or psychosis, greater than one lifetime, episode of major depression, current depression of moderate or greater severity (PHQ-9score of 10 or more), presence or history of suicidal behavior or ideation with some intent to act on it, or antidepressant use that has not been stable for at least 3 months will also be excluded.

22. Inability or refusal to comply with protocol

23. Current participation or participation in an experimental drug study in previous three months

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