A Phase I Study to Evaluate the PK and PD of a Single Injection of Levonorgestrel Butanoate for Female Contraception

Inclusion Criteria:

1. Good general health

2. Aged 18-44 years, inclusive, at the enrollment visit

3. Intact uterus with at least one ovary

4. Serum progesterone value ≥ 3 ng/mL at the Screening Visit (V0-P)

5. Pap test within the last 12 months or undergo a Pap test at screening prior toenrollment. If a potential subject states that she has had a Pap test within the last 12 months, then she will need to provide documentation of acceptable test results

6. Cervical mucus score of >7, which is based on the modified Insler scoring systemduring the screening cycle. The cervical mucus is collected by aspiration and theassessment is based on the modified Insler scoring system (the volume and pH of themucus are not included in the total scoring) yielding a total possible score of 12 (3,

7. Regular menstrual cycles that occur every 24 - 35 days

8. If subject is postpartum or post-abortal (with abortion in second trimester), shewill be required to have two normal menstrual cycles prior to screening

9. If subject had an abortion in the first trimester, she will be required to haveat least one menstrual cycle (two menses) prior to screening

10. Heterosexually abstinent or, if heterosexually active, must have undergone previoustubal sterilization, be in monogamous relationship with a vasectomized partner, oronly use male or female condoms (use of condoms that are pre-lubricated with orwithout spermicide is acceptable) for the entire duration of the study. Use of aspermicide applied separately is not allowed. Cervical caps or diaphragms are notallowed during study participation

11. In the opinion of the investigator, able to comply with the protocol, willing torecord requested information in the daily diary, and live within the study sitecatchment area or within a reasonable distance from the site

12. Understand and sign an IRB approved informed consent form prior to screeningactivities (including fasting blood draw)

13. Willing to refrain from use of any vaginal creams, lubricants, gels, or spermicidesfor 3 days prior to study admission through to the end of the study

14. Agree not to participate in any other clinical trials during the course of this study

Exclusion Criteria:

1. Known hypersensitivity or contraindication to progestins

2. Known or suspected pregnancy

3. Prior hysterectomy or bilateral oophorectomy

4. Prior cervical surgery (LEEP, Cone biopsy)

5. A history (within prior 12 months) of drug or alcohol abuse

6. Undiagnosed abnormal genital bleeding

7. Undiagnosed vaginal discharge or vaginal lesions or abnormalities. Subjects diagnosedat screening with a Chlamydia or gonococcus infection may not be included in the trialunless they are treated and proof of cure is documented after treatment (i.e. repeattest with negative results). In accordance with PI/medical designee assessment andlocal standards of practice, women with a history of genital herpes can be included ifoutbreaks are infrequent. Antiviral prophylactic therapy is permitted

8. Uncontrolled thyroid disorder

9. Any Pap test finding that would require additional workup or treatment during thestudy interval. HPV testing will not be done at screening for these subjects

10. Use of an injectable hormonal contraceptive (Depo-Provera®) within the past 10 months

11. Use of oral contraceptives, contraceptive implants, or other sex steroid hormoneswithin 30 days prior to screening visit

12. Women who are breastfeeding or within 30 days of discontinuing breast feeding

13. Women planning to undergo major surgery within four months of study enrollment

14. Women planning pregnancy within their months of study enrollment

15. Smoking in women who are ages 18-44 years old that smoke 15 cigarettes or more per daymust be evaluated by the PI for inclusion based on risk factors that would increasetheir risk for cardiovascular (CVD) and thromboembolism

16. Current or past deep vein thrombophlebitis or thromboembolic disorders

17. History of known thrombophilia in a first-degree relative <45 years of age suggestingfamilial defect in blood coagulation system, which in the opinion of the principalinvestigator, suggests use of a hormonal contraceptive could pose a significant risk

18. Cerebrovascular or cardiovascular disease or increased risk for arterial thrombosis

19. History of retinal vascular lesions, unexplained partial or complete loss of vision

20. Known or suspected carcinoma of the breast, endometrium, or any other known orsuspected progestin-dependent neoplasia

21. Past history of any other carcinoma (excluding basal cell carcinomas) unless inremission for more than 5 years

22. Current or past medically diagnosed severe depression, which, in the opinion of theinvestigator, could be exacerbated by use of a hormonal contraceptive, unless she isstable on antidepressant medication

23. Headaches with focal neurological symptoms only in women over 35 years old

24. History of cholestatic jaundice of pregnancy or jaundice with prior steroid use orother benign or malignant liver tumors; active liver disease

25. Systolic BP > 140 mm Hg and/or Diastolic blood pressure (BP) > 90 mm Hg after 5-10minutes rest

26. Clinically significant abnormal serum chemistry values according to the PrincipalInvestigator's judgment

27. Participation in another clinical trial involving an investigational drug or devicewithin last 30 days (prior to screening)

28. Use of liver enzyme inducers within last 90 days (prior to screening) or intention touse liver enzyme inducers during the study

29. Known HIV infection

30. Women at high risk of contracting HIV, e.g. women with multiple sex partners who needto use condoms consistently, injection drug users. Women enrolled in the study, whouse condoms to protect against STIs or pregnancy, should be instructed that they canuse condoms that are pre-lubricated with spermicide or lubricated, but they cannot usea spermicide applied separately and they should record all condom use in their diaries

31. Women who use any medications on the Exclusionary Medication List OR used any withinthe past three months prior to the screening visit

32. Women with BMI ≥40 kg/m2 are excluded

33. Have issues or concerns (in the judgment of the investigator) that may compromise thesafety of the subject or confound the reliability of compliance and informationacquired in this study