Clinical trial: 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 (NCT00796133)

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
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 40 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction