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
Condition: Endometriosis
MeSH terms: Endometriosis
Intervention: BAY1817080; Elagolix; Placebo
Intervention description: Tablet, oral administration; Tablet, oral administration; Tablet, oral administration
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double blind to placebo and open-label for active comparator
Enrollment: 215.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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