A Multi-center, Open-label, Randomized, Parallel Group Study to Evaluate Pharmacokinetic Profile, Effects on the Mechanisms of Contraceptive Efficacy and Safety of Two Progestin-only Patches Containing Different Doses of Levonorgestrel (LNG)

Contraindications for enrollment will be the same as those for use of combined hormonal contraceptives as referenced in the World Health Organization (WHO) Medical Eligibility Criteria(MEC category 1 or 2) (1), in addition to contra-indications specific to this clinical trial including:

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, Cryosurgery).

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

6\. Undiagnosed abnormal genital bleeding.

7\. Undiagnosed vaginal discharge or vaginal lesions or abnormalities. Subjects diagnosed at screening with a Chlamydia or gonococcus infection may not be included in the trial unless they are treated and proof of cure is documented after treatment (i.e. repeat test with negative results). In accordance with PI/medical designee assessment and local standards of practice, women with a history of genital herpes can be included if outbreaks are infrequent. Antiviral prophylactic therapy is permitted.

8\. Uncontrolled thyroid disorder.

9\. History or presence of dermal hypersensitivity in response to topical application. Specifically any reaction to application of a plastic bandage (Band-Aid), surgical or bandage tape, other skin patches, or adhesives.

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

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

12\. Use of oral contraceptives, contraceptive implants, or other sex steroid hormones within 30 days prior to screening visit.

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

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

15\. Women planning pregnancy within their months of study enrollment.

16\. Smoking in women who are ages 18-44 years old that smoke 15 cigarettes or more per day must be evaluated by the PI for inclusion based on risk factors that would increase their risk for CVD and thromboembolism.

17\. Current or past deep vein thrombophlebitis or thromboembolic disorders.

18\. History of known thrombophilia in a first-degree relative \<45 years of age suggesting familial defect in blood coagulation system, which in the opinion of the principal investigator, suggests use of a hormonal contraceptive could pose a significant risk.

19\. Cerebrovascular or cardiovascular disease or increased risk for arterial thrombosis.

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

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

22\. Past history of any other carcinoma (excluding basal cell carcinomas) unless in remission for more than 5 years.

23\. Current or past medically diagnosed severe depression, which, in the opinion of the investigator, could be exacerbated by use of a hormonal contraceptive, unless she is stable on antidepressant medication.

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

25\. History of cholestatic jaundice of pregnancy or jaundice with prior steroid use or other benign or malignant liver tumors; active liver disease.

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

27\. Clinically significant abnormal serum chemistry values according to the Principal Investigator's judgment.

28\. Participation in another clinical trial involving an investigational drug or device within last 30 days (prior to screening).

29\. Use of liver enzyme inducers within last 90 days (prior to screening) or intention to use liver enzyme inducers during the study (see Appendix 2 Exclusionary Medication List).

30\. Known HIV infection.

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

32\. Women who use any medications on the Exclusionary Medication List (see Appendix 2) OR used any within the past three months prior to the screening visit.

33\. Women with BMI ≥40 kg/m2 are excluded.

What this study is about