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

• Status: Not yet recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: Female

Summary

The pharmacodynamic endpoint of percentage of subjects with suppressed estradiol level (less than 20 pg/mL) on cycle day 29 is the primary endpoint of the study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Enteris BioPharma Inc.
• Collaborators: Parexel; Syneos Health
• Treatments: Leuprolide

Criteria

Inclusion criteria:

1. Women diagnosed with endometriosis and having pelvic pain, both treatment naive or previously treated with GnRH agonists or antagonists with improvement.

2. Premenopausal females in general good health, aged 18 to 49 years

3. BMI ≥18 and ≤35 kg/m2, and weight ≥110 lb. (≈50 kg).

4. A documented estradiol level ≥ 40 pg/mL at screening or on retest

5. Regular menstrual cycles with a usual length ranging from 21 days to 35 days. If subject has recently used hormonal birth control, historical data prior to use will be used to determine qualification and must also meet this criterion.

6. If of childbearing potential and sexually active with a risk of pregnancy, willing to use acceptable methods of contraception

7. Willing to refrain from excessive use of alcohol during the entire study and willing to refrain from use of alcohol 24 hours prior to any PK blood draw taken during the study

8. Willing to refrain from use of prescription medications, over-the-counter medications and natural health products which are known to or suspected of affecting estradiol or gonadotropin levels during the entire study

9. Willing and able to adhere to medication schedule and to utilize the AiCure medication adherence monitoring platform correctly with the administration of each dose of medication throughout the duration of the 3 treatment cycles comprising this study

10. Willing and capable to give informed consent to participate in study

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.

2. Undiagnosed abnormal vaginal bleeding.

3. Known or suspected pregnancy, or subjects who are considering becoming pregnant prior to the conclusion of this study.

4. Breastfeeding or within 2 months after stopping breastfeeding (relative to the screening visit).

5. Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions.

6. Markedly impaired liver function or liver disease.

7. 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. Use of an estrogen preparation within 2 months prior to screening

39. 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

40. Current use of any prescription medication known to cause delayed gastric emptying (e.g. glucagon-like peptide-1 receptor agonists)