Mirena for the Treatment of Nonatypical Endometrial Hyperplasia for 6 Months (SUNFLOWER)

A Multi-center, Open Label, Randomized Parallel Group Study Evaluating the Proportion of Women With Complete Resolution of Nonatypical Endometrial Hyperplasia Treated With Mirena or Oral Medroxyprogesterone Acetate for 6 Months

Researchers are looking for a better way to treat women with nonatypical endometrial hyperplasia (NAEH).

Endometrial hyperplasia is a condition where the lining of the uterus (called the endometrium) becomes too thick. Nonatypical means that the condition is not cancerous. It is often caused by hormone imbalances in women. Symptoms can include abnormal vaginal bleeding or irregular periods. If this condition is not treated, then it may lead to cancer.

Currently, there are no approved treatments for NAEH and that is why there is still an unmet medical need.

The study treatment, Mirena (also known as BAY 865028), is already available as a type of birth control device. It is inserted into the uterus where it gradually releases progesterone.

In this study, researchers want to find out if Mirena works for women with NAEH. They believe it can help by keeping hormone levels balanced in the body.

The main purpose of this study is to show that uterine lining goes back to completely normal lining after treatment with Mirena and that its use is safe in this population.

For this, the researchers will compare the number of participants with benign endometrium after 6 months of treatment with Mirena or oral MPA.

The study participants will be randomly assigned into one of two treatment groups. The randomization will be done 2:1 ratio, meaning that for every two participants assigned to Mirena, one will be assigned to oral medroxyprogesterone acetate (MPA). Based on their group, participants will receive Mirena, which is inserted into the uterus at the start of the study, or they will take progestins once daily by mouth for 6 months.

Each participant will be in the study for around 10 months with up to 5 visits to the study clinic/site.

Participants will visit the study clinic:

• once before the treatment starts
• 3 times with a gap of 3 months between the visits during the treatment
• then 1 more time after the treatment ends

During the study, the doctors and their study team will:

• check participant's health by performing tests such as blood and urine tests
• perform vaginal ultrasound and hysteroscopy. Hysteroscopy is a minor surgical procedure where a thin camera will be inserted into the womb to check for any abnormality. Sampling of the endometrial lining (cells in the womb) will be done with a thin tube at the same time.
• take samples of womb (endometrial) lining
• ask the participants questions about how they are feeling and what adverse events they are having

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment.

Study Overview

• Status: Withdrawn
• Conditions: Endometrial Hyperplasia
• Intervention / Treatment: Combination product: BAY865028; Drug: Medroxyprogesterone acetate

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 7W9
      • The Ottawa Hospital, Riverside Campus - Department of Obstetrics, Gynecology and Newborn Care
    • Toronto, Ontario, Canada, M5G 1Z5
      • Mount Sinai Hospital Toronto | Gynecology
  • Quebec
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Centres Investigation Clinique Mauricie
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • China-Japan Friendship Hospital
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital CAMS
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 401147
      • Chongqing Maternal and Child Health Care Hospital
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Xiamen Maternity and Child Health Care Hospital - Gynecology Department
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital of Southern Medical University - Gynecology Department
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
  • Hebei
    • Tangshan, Hebei, China, 063014
      • Tangshan Maternal and Child Health Care Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210004
      • Nanjing Maternity and Child Health Care Hospital
    • Nanjing, Jiangsu, China, 210011
      • Nanjing Medical University (NMU) - The Second Affiliated Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Maternal and Child Health Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710068
      • Shaanxi Provincial People's Hospital
  • Shandong
    • Qingdao, Shandong, China, 266034
      • Women and Children's Hospital, Qingdao University - Gynecology department
  • Sichuan
    • Chengdu, Sichuan, China, 610091
      • Chengdu Women & Children's Central Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Velocity Clinical Research - Phoenix
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Cornerstone Clinic for Women - Aldersgate
  • California
    • West Hills, California, United States, 91307
      • Alliance Clinical West Hills
  • Florida
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty, Inc. - Hialeah
    • Miami, Florida, United States, 33186
      • New Age Medical Research Corp.
    • Palmetto Bay, Florida, United States, 33176
      • Entrust Clinical Research
    • Panama City, Florida, United States, 32405
      • Emerald Coast Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Paramount Research Solutions | College Park Location
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Office of Dr. Cindy Basinski, LLC
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Velocity Clinical Research - Lafayette
    • Metairie, Louisiana, United States, 70001
      • Southern Clinical Research Associates
    • Shreveport, Louisiana, United States, 71118
      • Omni Fertility and Laser Institute
  • Michigan
    • Dearborn Heights, Michigan, United States, 48127
      • Revive Research Institute - Michigan - Women's Health
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Bosque Women's Care | Albuquerque, NM
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Unified Women's Clinical Research - Centre OB/GYN
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Clinical Research
  • Ohio
    • Columbus, Ohio, United States, 43213
      • ClinOhio Research Services, LLC. | Columbus, OH
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • OB/GYN Associates of Erie
  • Tennessee
    • Chattanooga, Tennessee, United States, 37412
      • Chattanooga Medical Research, LLC. | Chattanooga, TN
  • Texas
    • Dallas, Texas, United States, 75230
      • Discovery Clinical Trials - Dallas
    • Houston, Texas, United States, 77043
      • Biopharma Informatic - West Houston
    • Pearland, Texas, United States, 77584
      • AIH Research- Broadway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Post-menarchal women (≥18 years) at the time of signing the informed consent.
• Women with histologically confirmed NAEH independent of their parity or menopausal status. Endometrial samples will be obtained either at screening or no more than 42 days prior to the signing of the informed consent form.

Exclusion Criteria:

• Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results.
• Congenital or acquired uterine or cervical anomaly including fibroids, or cervical stenosis that in the opinion of the investigator, would interfere with insertion and/or retention of the intrauterine system (i.e., if they distort the uterine cavity).
• Use of any long-acting injectable sex-hormone preparations within 6 months prior to the start of study intervention, and /or short acting hormonal medication within 6 weeks prior to the start of study intervention.
• Pregnancy
• Participants with either known family or personal history of genetic predisposition to uterine, ovarian or colorectal cancers (e.g. Lynch syndrome).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levonorgestrel (BAY865028, Mirena); Mirena will be inserted into the participant's uterus by the investigator on Day 1. At visit 4 (after 6 months) or if a participant discontinues her study participation prematurely, the Mirena will be removed by the investigator.	Combination product: BAY865028; Intrauterine delivery system
Active Comparator: Oral progestin; Participants will receive 10mg oral progestin once daily, preferably always at the same time of the day, until visit 4 (after 6 months).	Drug: Medroxyprogesterone acetate; Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with Complete Resolution (CR) of NAEH	Complete Resolution will be evaluated as benign endometrium.	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of NAEH after CR	Recurrence of NAEH on 3 months treatment free after CR at 6 months	At 3 months follow up after 6 months treatment
Progression after CR	Endometrial hyperplasia with atypia or endometrial cancer after 3 months treatment free follow up after CR at 6 months	At 3 months follow up after 6 months treatment
Proportion of participants having hysterectomy		During treatment and 3 months follow up
Diagnosis of "benign endometrium"		At 6 months of treatment followed by 3 month treatment-free follow up
Number of participants with adverse events	All AEs will be coded using the latest version prior to database lock of the Medical Dictionary for Regulatory Activities	From the signing of the informed consent form (ICF) up to 3 months after the last dose of study intervention

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2025
• Primary Completion (Actual): June 17, 2026
• Study Completion (Actual): June 17, 2026

Study Registration Dates

• First Submitted: March 21, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Actual): July 30, 2026
• Last Update Submitted That Met QC Criteria: July 29, 2026
• Last Verified: July 22, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Endometrial Hyperplasia; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Medroxyprogesterone Acetate
• Other Study ID Numbers: 22923

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

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