Clinical trial: A Dose-finding Study to Evaluate the Effect of a Contraceptive Vaginal Ring, Releasing Nestorone® and Estradiol, on Cycle Control, Ovulation Inhibition, and Pharmacokinetics in Normal Cycling Women (NCT01586000)

Eligibility criteria:
Inclusion Criteria:

        Women who meet all the following criteria are eligible for enrollment in the trial:

          1. Healthy women of reproductive age (18-39 years, inclusive, at the enrollment visit).

          2. Have a regular menstrual cycle that is 21-35 days in duration.

          3. Have intact uterus and both ovaries.

          4. Will be able and willing to comply with the protocol and sign an informed consent.

          5. Will not be at risk for pregnancy. They will be consistently using a non-hormonal
             method, have a surgically sterile male partner with a vasectomy, be abstinent, or be
             in a same-sex relationship from the control period through study exit (including
             recovery period).

          6. Will have diastolic blood pressure (BP) ≤85 mm Hg and systolic BP ≤135 mm Hg after 5
             minutes in sitting position.

          7. Willing to abstain from use of non-water based vaginal lubricant during the study.

        Exclusion Criteria:

        Women who meet any of the following criteria are not eligible for enrollment in the trial:

          1. Participating in another clinical trial involving an investigational product within
             the last 30 days (prior to screening) or planning to participate in another clinical
             trial during this study.

          2. Not living in the catchment area of the clinic.

          3. Known hypersensitivity to progestins or estrogen.

          4. All contraindications to combined estrogen-progestin contraceptive use including:

               -  Thrombophlebitis or thromboembolic disorders.

               -  Past personal history of deep vein thrombophlebitis or thromboembolic disorders.

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

               -  History of stroke.

               -  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 oral contraceptive use.

               -  Hepatic adenomas or carcinomas.

               -  Known or suspected pregnancy.

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

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

               -  Headaches with focal neurological symptoms (e.g., migraines with auras).

          5. Desire to become pregnant during the study.

          6. Breastfeeding.

          7. 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. Subjects with vaginitis
             (yeast, trichomonas, or bacterial vaginitis) may be enrolled after treatment.
             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. 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.

          8. A clinically significant Pap test abnormality, as managed by current local or national
             guidelines. Women with a current abnormal Pap (within the last nine months):

               -  In accordance with the Bethesda system of classification: smear suggestive of
                  high-grade pre-cancerous lesion(s), including high grade squamous intraepithelial
                  lesions (HGSILs), are excluded;

                    -  Women with low grade squamous intraepithelial lesion (LGSIL) or atypical
                       squamous cells of undetermined significance (ASCUS)/high-risk human
                       papillomavirus (HPV) positive, or Atypical squamous cells, cannot rule out a
                       high grade lesion (ASC-H) may participate if further evaluated with
                       colposcopy and biopsy determines no evidence of a lesion with a severity
                       greater than cervical intraepithelial neoplasia (CIN) I.

                    -  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 test may
                       participate following exclusion of a high grade lesion by colposcopic
                       evaluation based on Investigator discretion and provided there is
                       appropriate follow up in accordance with local standards.

          9. Known benign or malignant liver tumors; known active liver disease.

         10. Invasive cancer (past history of any carcinoma or sarcoma, except non-melanoma skin
             cancer).

         11. Current or past medically diagnosed severe depression, which, in the opinion of the
             investigator, could be exacerbated by use of a hormonal contraceptive.

         12. Known or suspected current alcoholism or drug abuse.

         13. Elevated serum fasting clinical chemistry values or complete blood count (CBC) values
             designated clinically significant by the investigator or medically qualified
             sub-investigator.

         14. Uncontrolled thyroid disease.

         15. Known impaired hypothalamic-pituitary-adrenal reserve.

         16. Body mass index (BMI) >35.

         17. Use of injectable contraceptives (e.g. cyclofem or depo-medroxyprogesterone acetate)
             during the 6 months prior to enrollment or no spontaneous menses since last injection.

         18. Use of oral contraceptives within one month prior to start of control cycle (subjects
             must undergo informed consent process and screening procedures before stopping oral
             contraceptives to participate in the study).

         19. Use of hormonal contraceptives. NOTE: Removal of implanted hormonal contraceptives
             must have been for personal reasons unrelated to the purpose of enrollment in this
             study.

         20. Current use of an intrauterine device (IUD). NOTE: Removal of an IUD must have been
             for personal reasons unrelated to the purpose of enrollment in this study.

         21. Known hypersensitivity to silicone rubber.

         22. History of toxic shock syndrome.

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

         24. Planning to undergo major surgery during the study.

         25. Severe constipation.

         26. Use of liver enzyme inducers or inhibitors on a regular basis.

         27. Known HIV infection.

         28. Bariatric surgery within the past year prior to enrollment.

         29. Any abnormalities found during the transvaginal ultrasound (TVUS) that the PI or
             medically qualified sub-investigator deems to put the subject at risk.

         30. Have issues or concerns (in the judgment of the investigator) that may compromise the
             safety of the subject or confound the reliability of compliance and information
             acquired in this study.
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 39 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