Clinical trial NCT02807363 (phase 2, status: completed)
Conditions: endometriosis
ICD codes: N80.8, N80.9, N80.0, N80.1, N80.5, N80.2, N80.3
Drugs: leuprolide oral tablet 4-mg qd, leuprolide oral tablet 4-mg bid, leuprolide depot, leuprolide oral tablet 10-mg bid
SMILES: CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O, CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O, CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O, CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O
Eligibility 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