A Phase 2, Dose-finding, Cross-over Study to Evaluate the Effect of a NES/E2 Transdermal Gel Delivery on Ovulation Suppression in Normal Ovulating Women

This is a Phase 2, dose-finding, cross-over study for the purposes of evaluating the effect of a NES/E2 transdermal gel delivery on ovulation suppression in normal ovulating women.


Eligibility Criteria:
Inclusion Criteria:

* Woman is between 18 and 40 years of age
* Has intact uterus and ovaries
* Has regular menstrual cycles of 25-35 days duration
* Able to comply with the protocol, including frequent blood sampling, and lives within the catchment area of the clinic
* Understands the study procedures and agrees to participate in the study by giving written informed consent
* Able to use non-hormonal, double-barrier contraceptives (e.g. condoms and diaphragm) with every act of intercourse, or has been sterilized with tubal ligation, or only male partner has been sterilized with vasectomy
* Progesterone \>10 nmol/L in at least one sample in the lead-in cycle

Exclusion Criteria:

* All contraindications to OC use including
* Thrombophlebitis or thromboembolic disorders
* Past history of deep vein thrombophlebitis or thromboembolic disorders
* Past or current cerebrovascular or coronary artery disease
* Known or suspected carcinoma of the breast
* Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
* Undiagnosed abnormal genital bleeding
* Cholestatic jaundice of pregnancy or jaundice with prior pill use
* Hepatic adenomas or carcinomas
* Woman has a history of headaches with focal neurological symptoms
* Known or suspected pregnancy
* Aged \>35 and smoker
* BMI \>29
* Positive urine pregnancy test at the screening or baseline visit
* Desired pregnancy within the duration of the study
* Known hypersensitivity to progestins
* Known hypersensitivity to estrogen
* Undiagnosed vaginal discharge or vaginal lesions or abnormalities
* In accordance with the Bethesda system of classification Women with a current abnormal Pap smear suggestive of high-grade pre cancerous lesion(s), including HGSIL, are excluded
* Women with LGSIL or ASCUS/high-risk HPV positive may participate if further evaluated with colposcopy and biopsy and no evidence of a lesion with a severity \>CIN I is present and/or endocervical curettage is negative
* Women with a biopsy finding of CIN I should have follow up for this finding per standard of care; women are excluded if treatment is indicated In accordance with other Pap class systems
* Women with high grade dysplasia are excluded
* Women with low grade dysplasia or CIN I interpretation on Pap smear may participate based on investigator discretion in accordance with local standard of care
* Breastfeeding
* Cancer (past history of any carcinoma or sarcoma)
* History of a significant psychiatric disorder, including severe depression.
* Chronic or acute liver or renal disease
* Hypertension-- controlled by medication or defined by diastolic BP 85 mm Hg or systolic BP 135mm Hg after 15 minutes rest
* Dermatitis, psoriasis or other severe skin disorder
* Known or suspected alcoholism or drug abuse
* Clinically significant abnormalities of laboratory safety tests
* Chronic disease or history of illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject
* Woman is participating or has participated in another clinical study (involving an investigational drug) within one month prior to enrollment.
* Use of injectable contraceptives during the previous 3 months (e.g. cyclofem) or 9 months (e.g. DMPA)
* Use of oral contraceptives within the past 1 month
* Use of concomitant drugs that may interact with the study drugs