A Study of Pharmacokinetic/Pharmacodynamic Profile of Orally Administered Leuprolide in Healthy Female Volunteers

• Status: Completed
• Trial end date: 2018-06-18
• Target enrollment: 0
• Participant gender: Female

Summary

This Phase 2a, pharmacokinetic/pharmacodynamic study will determine the safety and provide evaluation of the PK/PD metrics of three different oral doses selected upon the results of the study LOPDT-PH1-01 - 4 mg oral tablets administered over 28 days as QD and BID regimens and 10 mg oral tablets administered over 28 days as a BID regimen. The PK/PD profiles of the study drug will be compared to the leuprolide formulation approved for the treatment of endometriosis (a monthly intramuscular injection, Lupron Depot 3.75 mg). Major PK (e.g., a total exposure to leuprolide) and PD parameters (e.g., rates of the estradiol suppression and cessation of the menstrual period) will also be evaluated against the Lupron Depot historical data.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Enteris BioPharma Inc.
• Treatments: Leuprolide

Criteria

Inclusion Criteria:

1. Healthy premenopausal female volunteers, aged 18 to 49 years

2. Body mass index (BMI) ≥18 and ≤ 32 kg/m2, and weight ≥ 110 lbs. (≈50 kg).

3. 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.

4. If of childbearing potential and sexually active with a risk of pregnancy, willing to use one of the following acceptable methods of contraception throughout the study and for at least 30 days after the last drug administration:

1. intra-uterine contraceptive device without hormone release system placed at least 4 weeks prior to the first study drug administration with simultaneous use of condom for the male partner

2. simultaneous use of diaphragm with intravaginally applied spermicide and condom for the male partner

3. sterile male partner (vasectomized for at least 6 months);

5. 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

6. Willing to refrain from use of prescription medications, over-the-counter medications and natural health products during the entire study

7. Willing and capable

Exclusion Criteria:

1. Hypersensitivity to GnRH, GnRH agonist analogs 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 This is a contraindication from the Lupron Depot label

4. Breast-feeding or within 2 months after stopping breast-feeding (relative to the screening visit) Note: Use of LUPRON DEPOT is contraindicated in women who are breast-feeding.

5. Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions. Note: Per the LUPRON DEPOT label, a possible co-administration 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 co-administration of Norethindrone acetate is contraindicated in women with markedly impaired liver function or liver disease.

7. Known or suspected carcinoma of the breast. Per the LUPRON DEPOT label, a possible co-administration of Norethindrone acetate is contraindicated in women with known or suspected carcinoma of the breast.

8. Status post-partum or post-abortion within a period of 2 months prior to the screening visit

9. A cervical cytology smear of Papanicolaou (Pap) class III or greater or a Bethesda System report of low grade squamous intraepithelial lesions (SIL) or greater (PAP smear results within last 12 months are acceptable if properly documented)

10. Use of any tobacco products (including electronic cigarettes) in the 3 months preceding the screening visit or positive urine cotinine test at screening.

11. History of significant alcohol or drug abuse within one year prior to the screening visit.

12. Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening.

13. Any clinically significant history or presence of neurologic, endocrinologic, pulmonary, hematologic, immunologic, or metabolic disease

14. History of severe respiratory depression or pulmonary insufficiency.

15. Diabetes Mellitus requiring insulin

16. History of headaches with focal neurological symptoms

17. Uncontrolled thyroid disorder

18. Sickle cell anemia

19. Current or history of clinically significant depression in the last year

20. Known disturbance of lipid metabolism

21. Hepatic adenoma or carcinoma

22. Undiagnosed abnormal genital bleeding

23. Known or suspected endometrial carcinoma, or estrogen-dependent neoplasia

24. History of sensitivity to leuprolide acetate or other GnRH agonists

25. Clinically significant history or presence of any gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), 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.

26. Difficulty in swallowing study medication

27. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in this study

28. Positive test for hepatitis B, hepatitis C, or HIV at screening

29. Administration of any investigational drug and/or experimental device within 30 days prior to the screening visit

30. Administration of any biologics within 90 days prior to the screening visit

31. Clinically significant finding on the ECG suggesting participation in the study could pose a risk to the subject

32. A depot injection or an implant of any drug within 6 months prior to the screening visit

33. Use of oral contraceptives or other sex steroid hormones within 3 months prior to the screening visit

34. Any clinically significant physical or gynecological abnormality at the screening visit

35. Any clinically significant abnormal laboratory test result at the screening visit

36. Hemoglobin <115 g/L and/or hematocrit < 0.32 L/L

37. Use of prescription medication within 14 days prior to the first administration of study medication or over-the-counter products (including natural health products, e.g. food supplements, vitamins, herbal supplements) within 7 days prior to the first administration of study medication, except for topical products without significant systemic absorption

38. 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

39. Deemed by the Investigator to have questionable ability to comply with the study protocol