Study to Gather Information How Well Three Different Doses of BAY1817080 Given Twice Daily Over 12 Weeks Work in Comparison to an Inactive Pill (Placebo) and Elagolix in Women Suffering From Pain Related to a Condition Where the Tissue That Usually Grows Inside the Womb Grows Outside of the Womb

Phase 2

Terminated

Conditions: Endometriosis

Interventions: Drug: BAY1817080
Drug: Placebo
Drug: Elagolix

Registration Number: NCT04614246

Lead Sponsor: Bayer

Brief Summary: The purpose of this study is to assess safety and efficacy of BAY 1817080 compared to elagolix and placebo in women with symptomatic endometriosis. Study details include:

* Study duration: 155 up to 285 days

* Treatment duration: 84 days

* Visit frequency: 3 laboratory every 2 weeks for participants on BAY 1817080 or placebo

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 215

Inclusion Criteria

Participant must be ≥ 18 years of age at the time of signing the informed consent
Visually-confirmed endometriosis: detection of endometriotic lesions during laparoscopy or laparotomy (with or without pathological diagnosis) within 10 years but no less than 8 weeks from Visit 1a (surgically diagnosed endometriosis). For Japan only and limited to no more than half of all randomized Japanese participants: the diagnosis can be based on previous imaging (i.e. endometriosis lesion detected by ultrasound or MRI). If the participant was diagnosed by ultrasound, the lesion must be visualized again by ultrasound at the screening visit. If the participant was diagnosed by MRI, the diagnosis must have been made within 12 months before Visit 1a (clinically diagnosed endometriosis).
Both sub-criteria regarding pain symptoms must be fulfilled:
- At Visit 1a, participant presents self-reported moderate to severe pain which - based on the judgement of the investigator - carries a reasonable likelihood to translate into a severity of pain symptoms sufficient to fulfil the eligibility criterion and be caused by endometriosis, and
- During the screening period at least 24 daily ESD entries during the 28 consecutive days starting on the first day with menstrual bleeding at or after Visit 1a and entries in the ESD item 1a ('worst pain' on the daily numerical rating scale) sum up to 98 or more.
Willingness to use standardized rescue pain medications for EAPP (i.e. ibuprofen, acetaminophen and tramadol) and not use any prophylactic pain medication, according to investigator's instruction
Ability to swallow the study intervention, i.e., the different kinds of tablets, as complete units
Good general health (except for findings related to endometriosis) as proven by medical history, physical and gynecological examinations and laboratory test results
Normal or clinically insignificant cervical cytology not requiring further follow-up:
- A cervical cytology sample has to be obtained during screening, or
- A documented normal result has to be available from cervical cytology conducted within 12 months prior to Visit 1a.
- Human papilloma virus (HPV) testing in participants with atypical squamous cells of unknown significance (ASCUS) will be used as an adjunctive test automatically. Participants with ASCUS can be included if they are negative for high-risk HPV strains.

Exclusion Criteria

Current pregnancy or less than 3 months since delivery, abortion or stop of lactation before Visit 1a
Hypersensitivity to any ingredient of the study intervention and/or the standardized rescue medications
Known osteoporosis
History of a low trauma fracture
Contraindications for elagolix or the standardized rescue medications
Current malignancy or history of cancer (exception: basal cell or squamous cell carcinoma of the skin) within the last 5 years prior to Visit 1a
Any other diseases or conditions that according to the investigator can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study intervention (e.g. extremely low body weight, chronic bowel disease, Crohn's disease and ulcerative colitis)
Menopause or signs of menopausal transition, such as absence of regular menstrual cycles based on investigator's judgment (absence of information regarding menstrual bleeding pattern e.g. due to long term use of hormonal contraception is not an exclusion criterion)
Any disease or condition that may worsen during the study period according to the assessment and opinion of the investigator
Abnormal uterine bleeding in terms of regularity or heaviness (with the exception of heavy menstrual bleeding that does not require treatment)
Any findings that require further diagnostic procedures to avoid harm to the participant (e.g. ovarian tumors of uncertain origin or pelvic masses of unclear etiology)
Any serious or unstable diseases or medical conditions, including psychiatric disorders, that might interfere with the conduct of the study or the interpretation of the result, including for example:
- history of hysterectomy and/or bilateral oophorectomy
- any conditions considered to contribute significantly to pelvic pain by the investigator, e.g. fibromyalgia, uterine fibroids, irritable bowel syndrome or other bowel disorders
- any other underlying diseases requiring regular use of pain medication (e.g. migraine)
- history of or current anxiety or depression unless stable with or without medical treatment ≥ 6 months before Visit 1a
Major surgery scheduled during the study period
Non-responsiveness of EAPP to earlier treatment with GnRH-agonists or GnRH-antagonists, based on the judgement of the investigator
SARS-CoV-2- positive virus RNA test within 4 weeks prior to Visit 1a reported by participant, regardless of whether the participant had symptoms
History of COVID-19 infection with persistent/ongoing symptoms
Contact with SARS-CoV-2- positive or COVID-19 patient within the last 4 weeks prior to Visit 1a
Intake of medication prohibited due to potential drug-drug interaction
Use of other treatments that might interfere with the conduct of the study or the interpretation of the results, including:
- hormonal medications
- other treatments intended for endometriosis/pelvic pain during participation in the study, including the use of herbal products or traditional Chinese medicine for symptom relief, with the exception of the standardized rescue pain medications
Simultaneous participation in another clinical trial with investigational medicinal product(s). Participation in another trial 3 months prior to Visit 1a that might have an impact on the study objectives, at the discretion of the investigator
Previous assignment to study intervention (randomization) in this study (allowing previously randomized participants to be re-included into the study may lead to bias)
Laboratory values outside the inclusion range (specified in the laboratory manual) and considered clinically relevant

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BAY1817080 75 mg	BAY1817080	Participants will receive 75 mg of BAY1817080 twice daily over a 12-week intervention period
Placebo	Placebo	Participants will receive placebo matching BAY1817080 twice daily over a 12-week intervention period
Elagolix	Elagolix	Participants will receive 150 mg of Elagolix once daily over a 12-week intervention period
BAY1817080 150 mg	BAY1817080	Participants will receive 150 mg of BAY1817080 twice daily over a 12-week intervention period
BAY1817080 25 mg	BAY1817080	Participants will receive 25 mg of BAY1817080 twice daily over a 12-week intervention period

Primary Outcome Measures

Name	Time	Method
Absolute Change in Mean Worst Endometriosis Associated Pelvic Pain (EAPP), Primary Per Protocol Set (pPPS)	change from baseline to week 12	The worst EAPP was measured daily on the 0-10 Numerical Rating Scale (NRS) by item 1 of the Endometriosis Symptom Diary (ESD). In question 1, participants were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The absolute change in mean worst EAPP was from baseline (last 28 days before the first intake of study drug) to end of intervention (last 28 days ending with the last intake of study drug planned on Day 84 \[+3\]). The time frame of 28 days captures a menstrual cycle on average.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAE)	up to 14 days after the last study medication intake	A treatment-emergent AE (TEAE) was defined as any event arising or worsening after the start of study drug administration until 14 days after the last study medication intake.
Least Squares Mean (SE) Changes in Worst EAPP From Baseline to Week 12, Per Protocol Set	change from baseline to week 12	The worst EAPP was measured daily on the 0-10 Numerical Rating Scale (NRS) by item 1 of the Endometriosis Symptom Diary (ESD). In question 1, participants were asked to rate the pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. The absolute change in mean worst EAPP was from baseline (last 28 days before the first intake of study drug) to end of intervention (last 28 days ending with the last intake of study drug planned on Day 84 \[+3\]). The time frame of 28 days captures a menstrual cycle on average.

Trial Locations

Locations (144): Accel Research Sites - Cahaba Medical Care
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Mobile Ob-Gyn, PC
🇺🇸
Mobile, Alabama, United States
Precision Trials, AZ, LLC
🇺🇸
Phoenix, Arizona, United States
Diagnamics, Inc.
🇺🇸
Encinitas, California, United States
West Coast OB/GYN Associates
🇺🇸
San Diego, California, United States
Advanced Women's Health Institute
🇺🇸
Greenwood Village, Colorado, United States
Office of Dr. James A. Simon, MD
🇺🇸
Washington, District of Columbia, United States
Helix Biomedics, LLC
🇺🇸
Boynton Beach, Florida, United States
Alliance for Multispecialty Research, LLC - Fort Meyers
🇺🇸
Fort Myers, Florida, United States
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Accel Research Sites - Cahaba Medical Care
🇺🇸Birmingham, Alabama, United States