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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT02635386 (opens ClinicalTrials.gov in a new tab)Other idRP15-008Other idAZ ESR-14-10725

Overview

Status
Completed
Phase
Phase 3
Enrollment
119 participants (actual)
Sponsor
Woman's · Other
Design
Randomized · Single masking
Countries
1 country

United States

Start
22 Mar 2016
Primary completion
22 Jul 2020
Completion
9 Oct 2020
First posted
18 Dec 2015 (estimated)
Last update posted
29 Jan 2021
Conditions
Polycystic Ovary Syndrome · Obesity

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201620172018201920202021
  1. Ph 3

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

    NCT02635386

    22 Mar 2016 to 9 Oct 2020

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Exenatide once weekly (EQW )Drug
  • Dapagliflozin (DAPA)Drug
  • EQW plus DAPADrug
  • Dapagliflozin plus Glucophage (MET ER)Drug
  • Phentermine /Topiramate (PHEN/ TPM) ERDrug

Arms5

  • Experimental

    Exenatide once weekly (EQW )

    EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks

  • Experimental

    Dapagliflozin (DAPA)

    DAPA-10 mg oral pill once daily in am for 24 weeks

  • Experimental

    EQW plus DAPA

    EQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks

  • Experimental

    Dapagliflozin plus Glucophage (MET ER)

    Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks

  • Active comparator

    Phentermine /Topiramate (PHEN/ TPM) ER

    Combination Phentermine /Topiramate ER -7.5 mg/46mg pill once daily in am for 24 weeks

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Oral Disposition (Insulin Sensitivity-insulin Secretion) Index

    Time frame · 24 weeks of treatment

    Registry description

    An estimation of β-cell compensatory function, the insulin secretion-sensitivity index (IS-SI) will be derived by applying the concept of the oral disposition index to measurements obtained during the 2-h OGTT and calculated as the index of insulin secretion factored by insulin sensitivity (ΔINS/ΔPG 30 x Matsuda SIOGTT) from the OGTT. A higher score shows improved pancreatic insulin responsiveness relative to resistance.

Secondary outcomes(20)
  1. Absolute Body Weight

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on body weight at 24 weeks of treatment

  2. Body Mass Index (BMI)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment efficacy in reducing body mass at 24 weeks of treatment

  3. Change in Percent Body Weight

    Time frame · Change from baseline (time 0) to study end (24 weeks)

    Registry description

    Treatment effect on change in percent body weight from baseline

  4. Central Adiposity (Waist Circumference)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on loss of central adiposity after 24 weeks

  5. Waist-to-Hip Ratio (WHR)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment impact on central adiposity after 24 weeks

  6. Waist-to-Height Ratio (WHtR)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment impact on WHtR which is a measure of central adiposity

  7. Total Fat Mass (kg) Evaluated by DEXA

    Time frame · 24 weeks of treatment

    Registry description

    Treatment impact on total fat mass by DEXA

  8. Total Body Fat (%) by DEXA

    Time frame · 24 weeks of treatment

    Registry description

    Treatment impact on percent total body fat by DEXA

  9. Android-Gynoid Ratio (AGR) as Determined by DEXA

    Time frame · 24 weeks of treatment

    Registry description

    treatment impact on measure of central adiposity as determined by android/gynoid ratio

  10. Trunk/Leg Fat Ratio by DEXA

    Time frame · 24 weeks of treatment

    Registry description

    Treatment impact on trunk/limb ratio (measure of central adiposity) by DEXA

  11. Fasting Blood Glucose

    Time frame · 24 weeks of treatment

    Registry description

    Treatment impact on fasting concentration of glucose in the blood

  12. OGTT Mean Blood Glucose (MBG)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on MBG measured during the oral glucose tolerance test

  13. Fasting Insulin Sensitivity (HOMA-IR)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on the ratio HOMA-IR which is insulin resistance measure derived from fasting blood glucose and insulin and is calculated by insulin (mU/ml)\*glucose (mmol/L)/22,5. The higher thenumber the more insulin resistant.

  14. Matsuda Sensitivity Index Derived From the OGTT(SI OGTT)

    Time frame · 24 weeks of treatment

    Registry description

    The SI IOGTT is a measure of peripheral insulin sensitivity derived from the values of Insulin (microunits per milliliter) and Glucose (milligrams per deciliter) obtained from the OGTT and the corresponding fasting values. SI (OGTT) = 10,000/ \[(G fasting x I fasting) x (G OGTTmean x I OGTTmean)\], where fasting glucose and insulin data are taken from time 0 of the OGTT and mean data represent the average glucose and insulin values obtained during the entire OGTT. The square root is used to correct for nonlinear distribution of insulin, and 10,000 is a scaling factor in the equation. The higher value, the more sensitive to insulin.

  15. Corrected First Phase Insulin Secretion (IGI/HOMA-IR)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on insulin secretion from 0 to 30 minutes after glucose load corrected for by fasting insulin sensitivity. A higher score shows improved first phase insulin secretion in response to glucose

  16. Total Cholesterol Levels

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on blood concentrations of total cholesterol

  17. Triglyceride (TRG) Levels

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on blood concentrations of triglycerides

  18. Total Testosterone Concentrations

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on blood concentrations of total testosterone

  19. Dehydroepiandrosterone Sulfate (DHEA-S) Levels

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on blood concentrations of DHEA-S

  20. Free Androgen Index (FAI)

    Time frame · 24 weeks of treatment

    Registry description

    Treatment effect on FAI calculated from total testosterone divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 24 weeks of treatment

Oral Disposition (Insulin Sensitivity-insulin Secretion) Index

GroupValue (index score)Spread
Exenatide Once Weekly (EQW )47183
Dapagliflozin (DAPA)31190
EQW Plus DAPA50380
Dapagliflozin Plus Glucophage (MET ER)39585
Phentermine /Topiramate (PHEN/ TPM) ER54593
Secondary and other outcome results(7)
Secondary outcomeMean· 24 weeks of treatment

Absolute Body Weight

GroupValue (kilogram)Spread
Exenatide Once Weekly (EQW )100.43.7
Dapagliflozin (DAPA)102.64
EQW Plus DAPA993.7
Dapagliflozin Plus Glucophage (MET ER)101.23.8
Phentermine /Topiramate (PHEN/ TPM) ER974.1
Secondary outcomeMean· 24 weeks of treatment

Body Mass Index (BMI)

GroupValue (kilogram/meter squared)Spread
Exenatide Once Weekly (EQW )37.31.1
Dapagliflozin (DAPA)37.41.2
EQW Plus DAPA36.71.1
Dapagliflozin Plus Glucophage (MET ER)371.2
Phentermine /Topiramate (PHEN/ TPM) ER35.31.3
Secondary outcomeMean· Change from baseline (time 0) to study end (24 weeks)

Change in Percent Body Weight

GroupValue (percentage change in body weight)Spread
Exenatide Once Weekly (EQW )3.80.8
Dapagliflozin (DAPA)1.51.4
EQW Plus DAPA6.90.9
Dapagliflozin Plus Glucophage (MET ER)1.71.0
Phentermine /Topiramate (PHEN/ TPM) ER8.11.3
Secondary outcomeMean· 24 weeks of treatment

Central Adiposity (Waist Circumference)

GroupValue (centimeters)Spread
Exenatide Once Weekly (EQW )1043
Dapagliflozin (DAPA)1013.2
EQW Plus DAPA1063
Dapagliflozin Plus Glucophage (MET ER)101.33
Phentermine /Topiramate (PHEN/ TPM) ER973.4
Secondary outcomeMean· 24 weeks of treatment

Waist-to-Hip Ratio (WHR)

GroupValue (ratio)Spread
Exenatide Once Weekly (EQW ).83.016
Dapagliflozin (DAPA).79.017
EQW Plus DAPA.86.016
Dapagliflozin Plus Glucophage (MET ER).83.016
Phentermine /Topiramate (PHEN/ TPM) ER.81.018
Secondary outcomeMean· 24 weeks of treatment

Waist-to-Height Ratio (WHtR)

GroupValue (ratio)Spread
Exenatide Once Weekly (EQW ).64.018
Dapagliflozin (DAPA).61.02
EQW Plus DAPA.65.018
Dapagliflozin Plus Glucophage (MET ER).61.019
Phentermine /Topiramate (PHEN/ TPM) ER.59.021
Secondary outcomeMean· 24 weeks of treatment

Total Fat Mass (kg) Evaluated by DEXA

GroupValue (kilogram)Spread
Exenatide Once Weekly (EQW )47.62.4
Dapagliflozin (DAPA)47.82.6
EQW Plus DAPA45.92.4
Dapagliflozin Plus Glucophage (MET ER)482.5
Phentermine /Topiramate (PHEN/ TPM) ER44.52.8

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Exenatide Once Weekly (EQW )EQW- 2 mg subcutaneous (SC) injection once every seven days for 24 weeks Exenatide once weekly (EQW ): 2 mg SC injection every 7 days0 / 232 / 2310 / 23
Dapagliflozin (DAPA)DAPA-10 mg oral pill once daily in am for 24 weeks Dapagliflozin (DAPA): One pill (10 mg) by mouth daily (QD) in am0 / 230 / 2310 / 23
EQW Plus DAPAEQW- 2 mg SC injection once every seven days for 24 weeks DAPA-10 mg oral pill once daily in am daily for 24 weeks EQW plus DAPA: 2 mg SC injection every 7 days One pill (10 mg) by mouth QD in am0 / 220 / 2213 / 22
Dapagliflozin Plus Glucophage (MET ER)Combination DAPA / MET ER-10 mg /2000 mg oral pill daily with food for 24 weeks Dapagliflozin plus Glucophage (MET ER): DAPA/MET ER-5 mg /1000 mg - 1 pill by mouth in am with food for 4 weeks DAPA/MET ER-10 mg /2000 mg - 2 pills in am by mouth with food -final dose0 / 260 / 2614 / 26
Phentermine /Topiramate (PHEN/ TPM) ERCombination Phentermine /Topiramate ER -7.5 mg/46mg pill once daily in am for 24 weeks Phentermine /Topiramate (PHEN/ TPM) ER: PHEN 3.75/TPM ER 23mg - 1 pill by mouth once daily in am for 2 weeks. After 2 weeks, PHEN 7.5mg/TPM ER 46mg- 1 pill by mouth once daily in am0 / 252 / 2513 / 25

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2021

4 results

Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome.

Elkind-Hirsch et al. 2021The Journal of clinical endocrinology and metabolismcited by 74

PMID 34097062DOI 10.1210/clinem/dgab408PUB-34097062

Full text at the publisher4 results

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 45 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
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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