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

Inclusion Criteria

• Healthy premenopausal female volunteers, aged 18 to 49 years;
• Body mass index (BMI) ≥ 18 and ≤ 32 kg/m2, and weight ≥ 110 lb (approximately 50 kg);
• Regular menstrual cycles with a usual length ranging from 21 days to 35 days. If subject had recently used hormonal birth control, historical data prior to use were used to determine qualification and must also meet this criterion;
• 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:
• intrauterine contraceptive device (IUD) 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;
• simultaneous use of diaphragm with intravaginally applied spermicide and condom for the male partner starting at least 14 days prior to drug administration;
• sterile male partner (vasectomized for at least 6 months); Note: Surgically sterile subjects who have had a tubal ligation were considered of non-childbearing potential and were not required to use contraception;
• 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;
• Willing to refrain from use of prescription medications, over-the-counter medications, and natural health products during the entire study;
• Willing and capable to give informed consent to participate in study.

Exclusion Criteria

• Hypersensitivity to GnRH, GnRH agonist analogs, similar nonapeptides, or any of the excipients in Lupron Depot®. Note: This was a contraindication from the Lupron Depot® label;
• Undiagnosed abnormal vaginal bleeding. Note: This was a contraindication from the Lupron Depot® label;
• Known or suspected pregnancy, or subjects who were considered to become pregnant prior to the conclusion of this study. Note: Lupron Depot® was contraindicated in women who were or may become pregnant while receiving the drug. Lupron Depot® could cause fetal harm when administered to a pregnant woman. If this drug was 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;
• Breastfeeding or within 2 months after stopping breastfeeding (relative to the Screening visit). Note: Use of Lupron Depot® was contraindicated in women who were breastfeeding;
• Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions. Note: Per the Lupron Depot® label, a possible coadministration of norethindrone acetate was contraindicated in women with thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions
• Markedly impaired liver function or liver disease. Note: Per the Lupron Depot® label, a possible co-administration of norethindrone acetate was contraindicated in women with markedly impaired liver function or liver disease;
• Known or suspected carcinoma of the breast. Note: Per the Lupron Depot® label, a possible co-administration of norethindrone acetate was contraindicated in women with known or suspected carcinoma of the breast;
• Status postpartum or post-abortion within a period of 2 months prior to the Screening visit;
• 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 were acceptable if properly documented);
• Use of any tobacco products (including electronic cigarettes) in the 3 months preceding the Screening visit or positive urine cotinine test at Screening;
• History of significant alcohol or drug abuse within 1 year prior to the Screening visit;
• Clinically significant (CS) vital sign abnormalities (systoli