PRECISION-E2: Teverelix in Women With Endometriosis - Pharmacodynamics, Safety and Precision Medicine Correlates

Inclusion Criteria:

1. Female between the ages of 19 and 50 (premenopausal)

2. Has given written consent

3. Clinical diagnosis of endometriosis (laparoscopy or imaging) performed within 5 years of Screening

4. The participant must have dysmenorrhea or pelvic pain associated with endometriosis, of which either one or both should be at least "moderate" as determined by the investigator or sub-investigator using the B&B scale.

5. The participant must have maximum VAS score > 30 for pelvic pain associated with endometriosis

6. The participant has experienced a regular menstrual cycle (25 to 38 days) that should include menstrual bleeding of at least 3 consecutive days (at least 3 regular menstrual cycles to be confirmed)

7. Agrees to practice contraception, which does not include any form of hormonal contraception during the entire study period:

   1. Either by using double barrier contraception and in compliance with local guidelines,
   2. or, is truly sexually abstinent, when this is in line with the preferred and usual lifestyle of the patient

8. Is not expected to undergo gynaecological surgery or other surgical procedures for treatment of endometriosis (including ablation, shaving, or excision) during the study, including during the Follow-Up Period, and the participant does not desire such treatment during this time frame.

9. Agree to continue to use only the analgesic medication permitted by the protocol during the Treatment and Follow-up Periods

10. For patients who already participate or are willing to participate in the Emirati Genome Program (EGP, willing to participate in the Pharmacogenomic Study

Exclusion Criteria:

1. Subject is pregnant or breast feeding or is planning a pregnancy within the next 24 months or is less than 6 months postpartum, post-abortion, or post-pregnancy at the time of entry into the Screening Period.

2. Subject has breast fed in the previous six months

3. Subject has a history of previous non-response to Gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, Depot Medroxyprogesterone Acetate, or aromatase inhibitors as assessed by subject report of no improvement in dysmenorrhea or non-menstrual pelvic pain (subject report of partial response to or side effects from these agents is not exclusionary).

4. Subject has chronic pelvic pain that is not caused by endometriosis that requires chronic analgesic or other chronic therapy, or that would interfere with the assessment of endometriosis related pain.

5. Known clinically significant gynaecologic condition, PID, abnormal genital bleeding or uterine anomaly

6. Bone mineral density by dual energy x-ray absorptiometry Z score of less than -2 at the lumbar spine, total hip or femoral neck

7. Subject has a history of osteoporosis or other metabolic bone disease

8. BMI <17 or > 35

9. Participated in another investigational study within 3 months before recruitment

10. Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values:

    1. Liver function test (aspartate aminotransferase [ASAT/SGOT], alanine aminotransferase [ALAT/SGPT]), exceeding >2X the upper limit of the normal (ULN) range
    2. Total bilirubin exceeding >1.5X the upper limit of the normal (ULN) range
    3. An estimated glomerular filtration rate (eGFR) < 30 mL/min, based on creatinine clearance calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation normalised to an average surface area of 1.73m2, at the screening visit.

11. Has congenital long QT syndrome or ECG abnormalities at screening

12. Use of the following medications prior to and during study participation:

    1. Any other IMP (within 3 months of enrolment)
    2. Herbal medications known to have anti-androgenic effects
    3. Bethanechol chloride
    4. Any other medication or herbal product that may affect hormone levels and might, therefore, confound interpretation of the study results (e.g. St. John's wort) (within 3 months of enrolment)