Study to Evaluate the Pharmacodynamics and Efficacy of Leuprolide Tablets (Ovarest®) in Women With Endometriosis

Exclusion Criteria

• •Subjects to whom any of the following applies will be excluded from the study:
• •1. Hypersensitivity to GnRH, GnRH agonist analogs, similar nonapeptides, or any of the excipients in LUPRON DEPOT. Note: This is a contraindication from the Lupron Depot label.
• •2. Undiagnosed abnormal vaginal bleeding. Note: This is a contraindication from the Lupron Depot label.
• •3. Known or suspected pregnancy, or subjects who are considering becoming pregnant prior to the conclusion of this study. Note: LUPRON DEPOT is contraindicated in women who are or may become pregnant while receiving the drug. LUPRON DEPOT may cause fetal harm when administered to a pregnant woman…. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
• •4. Breastfeeding or within 2 months after stopping breastfeeding (relative to the screening visit). Note: Use of LUPRON DEPOT is contraindicated in women who are breastfeeding.
• •5. Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions. Note: Per the LUPRON DEPOT label, a possible coadministration of norethindrone acetate is contraindicated in women with thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions.
• •6. Markedly impaired liver function or liver disease. Note: Per the LUPRON DEPOT label, a possible coadministration of norethindrone acetate is contraindicated in women with markedly impaired liver function or liver disease.
• •7. Known or suspected carcinoma of the breast. Note: Per the LUPRON DEPOT label, a possible coadministration of norethindrone acetate is contraindicated in women with known or suspected carcinoma of the breast.
• •8. Status postpartum or postabortion within a period of 2 months prior to the screening visit
• •9. History of significant alcohol or drug abuse within one year prior to the screening visit
• •10. Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mm Hg, diastolic blood pressure lower than 50 or over 90 mm Hg, or heart rate less than 50 or over 100 bpm) at screening (following recheck after five minutes at rest)
• •11. Any clinically significant history or presence of neurologic, endocrinologic, pulmonary, hematologic, immunologic, or metabolic disease
• •12. History of severe respiratory depression or pulmonary insufficiency
• •13. Diabetes mellitus requiring insulin
• •14. History of headaches with focal neurological symptoms
• •15. Uncontrolled thyroid disorder
• •16. Sickle cell anemia
• •17. Current or history of clinically significant depression in the last year
• •18. Known disturbance of lipid metabolism
• •19. Hepatic adenoma or carcinoma
• •20. Known or suspected endometrial carcinoma or estrogen-dependent neoplasia
• •21. Clinically significant history or presence of any gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel diseases, history of cholecystectomy), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting) or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug
• •22. Difficulty in swallowing study medication
• •23. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in this study
• •24. Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening
• •25. Administration of any investigational drug and/or experimental device within 30 days prior to the screening visit
• •26. Administration of any biologics within 30 days prior to the screening visit. Note: The Covid-19 vaccine is not included in this prohibition.
• •27. Clinically significant finding on the ECG suggesting participation in the study could pose a risk to the subject
• •28. A depot injection or an implant of any drug within 1 month prior to the screening visit
• •29. Use of oral contraceptives or other sex steroid hormones within 1 month prior to the screening visit. Note: A 1-month drug holiday period is mandatory for potential subjects receiving GnRH agonists and GnRH antagonists.
• •30. Any clinically significant physical or gynecological abnormality at the screening visit
• •31. Any clinically significant abnormal laboratory test result at the screening visit
• •32. Hemoglobin \<11.5 g/dL and/or hematocrit \<32%
• •33. Use of over-the-counter products containing any substances which could have the propensity to impact either estradiol or gonadotropin level
• •34. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing
• •35. History of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors
• •36. Significant risk factors for decreased bone mineral content and/or bone mass, such as family history (in a first degree relative) of osteoporosis, personal history of chronic use of corticosteroids or anticonvulsants
• •37. Participation in another drug research within 1 month prior to screening
• •38. Deemed by the Investigator to have questionable ability to comply with the study protocol, including inadequate adherence to both dosing and use of the AiCure medication adherence monitoring platform during the Run-in Period or during the three Treatment Cycles
• •39. Current use of any prescription medication known to cause delayed gastric emptying (e.g. glucagon-like peptide-1 receptor agonists)