Clinical trial: Safety and Efficacy of a Contraceptive Vaginal Ring Delivering Nestorone® and Ethinyl Estradiol (NCT00263341)

Eligibility criteria:
Inclusion Criteria:

        Healthy women who meet the following criteria:

          -  Aged 18-<40 years who wish to use a combined hormonal contraceptive.

          -  Women not intending to become pregnant for 13 months.

          -  Intact uterus and both ovaries.

          -  Prior history of regular menstrual cycles of 28 ± 7 days when not using hormonal
             contraception; if postpartum or postabortal, history of regular menstrual cycles of
             21-35 days in length and at least one cycle (2 menses) with a cycle length consistent
             with her past cycles.

          -  Sexually active (currently) and willing to discontinue current contraceptive method to
             participate in the study.

          -  In the opinion of the investigator, able to comply with the protocol, e.g. live within
             the clinic catchment area or within a reasonable distance from the clinic.

          -  Do not meet any of the exclusion criteria.

          -  Signed informed consent prior to entry into the trial.

        [For pharmacokinetics study only; 39 subjects already recruited]

        - Willing to undergo frequent blooding sampling

        Exclusion Criteria:

        Contraindications for enrollment will be the same as those for use with combined hormonal
        contraceptives in addition to contraindications specific to this clinical trial including:

          -  Known hypersensitivity to estrogens or progestins.

          -  Known hypersensitivity to silicone rubber.

          -  Known or suspected pregnancy.

          -  History of infertility of >1.0 year in woman or her male partner.

          -  History of vasectomy or sterility in male partner; tubal ligation (sterilization) in
             women.

          -  Undiagnosed abnormal genital bleeding.

          -  Undiagnosed vaginal discharge or vaginal lesions or abnormalities. (Subjects diagnosed
             at screening with a chlamydia or gonococcus infection may be included in the trial
             following treatment; partner treatment is also recommended. Investigators should make
             a determination if subjects are at high risk for reinfection, e.g. multiple sex
             partners, untreated partner, and whether such subjects can be included.)

          -  History of pelvic inflammatory disease since last pregnancy episode.

          -  History of toxic shock syndrome.

          -  Current abnormal Pap smear (women who have abnormal Paps but are ASCUS HPV negative
             may participate provided there is follow up for this finding per standard of care).

          -  Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a
             vaginal ring.

          -  Women planning to undergo major surgery.

          -  Smoking in women who are 35 years and over or will be 35 years during the course of
             the trial; women < 35yrs who smoke 15 cigarettes or more must be evaluated by the PI
             for inclusion based on risk factors that would increase their risk for CVD, e.g. lipid
             levels, glucose level, BP, BMI, family history of CVD at a young age.

          -  Breastfeeding.

          -  Current or past thrombophlebitis or thromboembolic disorders.

          -  History of venous thrombosis or embolism in a first-degree relative, <55 years of age
             suggesting a familial defect in the blood coagulation system, which in the opinion of
             the PI, suggests use of a hormonal contraceptive could pose a significant risk.

          -  Cerebrovascular or cardiovascular disease.

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

          -  Known or suspected carcinoma of the breast.

          -  Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia.

          -  Past history of any other carcinoma unless in remission for more than 5 years.

          -  Current or history of medically diagnosed severe depression, which, in the opinions of
             the investigator, could be exacerbated by use of a hormonal contraceptive.

          -  Headaches with focal neurological symptoms.

          -  Severe constipation.

          -  History of cholestatic jaundice of pregnancy or jaundice with prior steroid use.

          -  Benign or malignant liver tumors; active liver disease.

          -  Diastolic blood pressure (BP) 85 mm Hg and/or systolic BP 135 mm Hg after 5-10 minutes
             rest.

          -  Known or suspected alcoholism or drug abuse.

          -  Abnormal serum chemistry values according to the physician's judgment.

          -  Participation in another clinical trial within last 30 days.

          -  Weight >95 kg or >209 lbs.

          -  Use of liver enzyme inducers on a regular basis.

          -  Use of monthly injectable contraceptives (e.g. cyclofem) unless suspended 2 months
             before initiation of treatment. Use of Depo-Provera [depo-medroxyprogesterone (DMPA)]
             unless suspended 6 months before treatment.

          -  Current use of implanted hormonal contraceptives, including Mirena® [progestin
             containing intrauterine system (IUS)], Jadelle®, Norplant® or Implanon® (subjects
             using any of these methods who request removal for reasons unrelated to the purpose of
             enrollment in this study may be considered for participation).

          -  Current use of a non-hormonal IUD. Subjects with IUDs who request removal for reasons
             unrelated to the purpose of enrollment in this study may be considered for
             participation.

          -  Known HIV infection.

          -  Women at high risk of contracting HIV, e.g. women with multiple sex partners who need
             to use condoms consistently, injection drug users. If women enrolled in the study do
             use condoms to protect against STIs, they should be instructed that this occasional
             use should be with non-N-9 containing condoms and they should record condom use in
             their diaries. Women found to have an STI at screening will be treated prior to
             inclusion in the study (with the exception of those infected with HIV).
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? 0