Dapagliflozin Efficacy and Action in PCOS (DEAP)

Efficacy and Safety of Dapagliflozin in Polycystic Ovary Syndrome: a Multicentre, Randomized, Placebo-controlled Trial

The purpose of this study is to assess the efficacy and safety of dapagliflozin on improving insulin resistance and hyperandrogenemia in obesity women with polycystic ovary syndrome.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. women aged 18 to 45 years;
2. Subjects with PCOS diagnosed by according to the Rotterdam criteria;
3. BMI ≥24 kg/m2 and/ or Homeostatic model assessment of insulin resistance (HOMA-IR) with a cutoff ≥2.5;
4. No pregnancy plan within the next 6 months;

Exclusion Criteria:

1. Congenital adrenal hyperplasia such as 21-hydroxylase deficiency, hyperprolactinemia, Cushing syndrome, androgen-producing tumors of the adrenal gland or ovary;
2. Other endocrine diseases include poorly controlled thyroid diseases (hyperthyroidism or hypothyroidism), acromegaly, type 2 diabetes;
3. Patients with a history of acute / chronic infection, severe cardio-cerebrovascular diseases and acute / chronic pancreatitis;
4. Taking any antidiabetic medication that would affect insulin resistance or hyperandrogenemia (i.e. TZD, GLP-1RA, DPP-4i, metformin) in the past one month;
5. Taking letrozole, clomiphene, oral contraceptive, glucocorticoid, gonadotropin, gonadotropin releasing hormone agonist, anti-androgen drug (spironolactone, cycloproterenone acetate, Flutamide etc.) and/or other drugs for PCOS in the past three months;
6. History of recurrent urinary tract infection;
7. History of malignant tumor;
8. Currently participating in weight loss programs or weight change in the past 3 months (> 5% current body weight) or have a history of gastrointestinal surgery.
9. Serious liver dysfunction or chronic kidney disease (AST or ALT > 3 times the upper limit of normal, or eGFR<30 ml/min/1.73 m2);
10. Women who are pregnant or plan to become pregnant;
11. Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data;
12. Participation in other clinical trial in the 4 weeks before randomization;
13. Patients who are unwilling or unable to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin (Participants will receive dapagliflozin 10mg po qd).	Drug: Dapagliflozin; Participants will receive dapagliflozin 10mg po qd. Additionally, participants will receive lifestyle modification and nutrition education.
Placebo Comparator: Placebo; Placebo (Participants will receive placebo po qd)	Drug: Placebo; Participants will receive placebo po qd. Additionally, participants will receive lifestyle modification and nutrition education.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in insulin resistance over 12 weeks	Change in insulin resistance assessed by insulin sensitivity index(HOMA-IR)	Baseline and 12 weeks
Improvement in serum androgen level over 12 weeks	Change in androgen level assessed by free testosterone index(FAI)	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in AUC (area under a curve) of glucose and insulin during the oral glucose tolerant test (OGTT)		Baseline to 12 week
Change in serum free testosterone(FT)		Baseline to 12 week
Change in serum sex hormone binding globulin(SHBG)		Baseline to 12 week
Net change in total testosterone (TT) level		Baseline and 12 weeks
Net change in dehydroepiandrosterone-sulfate(DHEAS) level		Baseline and 12 weeks
Net change in luteinzing hormone(LH) level		Baseline and 12 weeks
Net change in waist circumference		Baseline to 12 week
Net Change in liver fat	Liver fat will be assessed by liver fibroscan.	Baseline to 12 week
Change in ovulation rate assessed by serum progesterone		Baseline to 12 week
Net change in body weight		Baseline to 12 week
Net change in BMI		Baseline to 12 week
Net change in glucose		Baseline to 12 week
Net change in androstenedione(AD) level		Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2020
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 26, 2019
• First Posted (Actual): December 30, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Polycystic Ovary Syndrome; SGLT2 inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: NFEC-2019-243

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No