| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of pain related to endometriosis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Treatment of pain in the area below the belly button and between the hips in connection with endometriosis (a condition where the tissue that usually grows inside the womb grows outside of the womb) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10014788 |
| E.1.2 | Term | Endometriosis related pain |
| E.1.2 | System Organ Class | 100000004872 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the dose-response relationship and demonstrate efficacy of BAY 1817080 compared to placebo in women with symptomatic endometriosis |
|
| E.2.2 | Secondary objectives of the trial |
• To identify at least 1 superior effective dose of BAY 1817080 compared to placebo
• To evaluate the safety and tolerability of 3 doses of BAY 1817080 compared to placebo and elagolix 150mg in women with symptomatic endometriosis |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Participant must be ≥ 18 years of age at the time of signing the informed consent
2. 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).
3. 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.
4. 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
5. Ability to swallow the study intervention, i.e., the different kinds of tablets, as complete units
6. Good general health (except for findings related to endometriosis) as proven by medical history, physical and gynecological examinations and laboratory test results
7. 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. |
|
| E.4 | Principal exclusion criteria |
1. Current pregnancy or less than 3 months since delivery, abortion or stop of lactation before Visit 1a
2. Hypersensitivity to any ingredient of the study intervention and/or the standardized rescue medications
3. Known osteoporosis
4. History of a low trauma fracture
5. Contraindications for elagolix or the standardized rescue medications
6. 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
7. Any other disease or condition 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. excessively low body weight, chronic bowel diseases, Crohn’s disease and ulcerative colitis)
8. 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)
9. Any disease or condition that may worsen during the study period according to the assessment and opinion of the investigator
10. Abnormal uterine bleeding in terms of regularity or heaviness (with the exception of heavy menstrual bleeding that does not require treatment)
11. 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)
12. 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
13. Major surgery scheduled during the study period
14. Non-responsiveness of EAPP to earlier treatment with GnRH-agonists or GnRH-antagonists, based on the judgement of the investigator
15. SARS-CoV-2- positive virus RNA test within 4 weeks prior to Visit 1a reported by participant, regardless of whether the participant had symptoms.
16. History of COVID-19 infection with persistent/ongoing symptoms
17. Contact with SARS-CoV-2- positive or COVID-19 patient within the last 4 weeks prior to Visit 1a
18. Intake of medication prohibited due to potential drug-drug interaction
19. 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
20. 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
21. Previous assignment to study intervention (randomization) in this study (allowing previously randomized participants to be re-included into the study may lead to bias)
22. Laboratory values outside the inclusion range (specified in the laboratory manual) and considered clinically relevant |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Absolute change in mean worst EAPP from end of intervention to baseline (measured daily on the NRS by item 1 of the ESD) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At baseline (last 28 days before start of study drug) and at day 57-84 (+3) |
|
| E.5.2 | Secondary end point(s) |
| Number of participants with treatment emergent adverse events |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| After the start of study drug administration until 14 days after the last study medication intake, assessed up to 98 days |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Double blind to placebo and open-label active comparator |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 93 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Belgium |
| Bulgaria |
| Canada |
| China |
| Czechia |
| Denmark |
| Estonia |
| Finland |
| Germany |
| Greece |
| Hungary |
| Ireland |
| Italy |
| Japan |
| Latvia |
| Lithuania |
| Netherlands |
| Norway |
| Poland |
| Portugal |
| Slovakia |
| Spain |
| Sweden |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study is defined as the date of the last visit of the last participant in the study globally |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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