Annovera™ Drug-Drug Interaction Study

Exclusion Criteria

• •Contraindications for enrollment will be the same as those for use of CHCs and additional criteria important to the objectives of this study and include:
• •a. Known hypersensitivity to estrogens or progestins.
• •b. Pregnant, trying to become pregnant, or breastfeeding.
• •c. Known hypersensitivity to silicone rubber.
• •d. Undiagnosed abnormal vaginal bleeding.
• •e. Undiagnosed vaginal discharge, vaginal lesions or abnormalities. Participants 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 participants are at high risk for reinfection, eg, multiple sex partners, untreated partner, and whether such participants can be included.
• •f. History of pelvic inflammatory disease since the participant's last pregnancy.
• •g. History of toxic shock syndrome.
• •h. In accordance with the Bethesda system of classification: Women with a current (within the last 20 months) abnormal Papanicolaou smear (Pap smear) suggestive of high-grade pre-cancerous lesion(s), including high grade squamous intraepithelial lesion.
• •i. Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a vaginal ring.
• •j. Women planning to undergo major surgery during the trial.
• •k. Current or past thrombophlebitis or thromboembolic disorders.
• •l. 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 Principal Investigator (PI), suggests that use of a hormonal contraceptive could pose a significant risk.
• •m. Cerebrovascular or cardiovascular disease.
• •n. History of retinal vascular lesions, unexplained partial or complete loss of vision.
• •o. Known or suspected carcinoma of the breast.
• •p. Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia.
• •q. Past history of any other carcinoma unless in remission for more than five years.
• •r. Current or history of medically diagnosed severe depression, which, in the opinion of the Investigator, could be exacerbated by the use of a hormonal contraceptive.
• •s. Has a Type D personality type as assessed by the DS14 test (Standard Assessment of Negative Affectivity, Social Inhibition and Type D Personality).
• •t. Headaches with focal neurological symptoms.
• •u. Severe constipation in the opinion of the Investigator.
• •v. History of cholestatic jaundice of pregnancy or jaundice with prior steroid use.
• •w. Benign or malignant liver tumors; active liver disease.
• •x. Diastolic blood pressure (BP) \> 85 mm Hg and/or systolic BP \> 135 mm Hg after 5 to 10 minutes rest (at Screening).
• •y. Known or suspected alcoholism or drug abuse within their lifetime, or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine, crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening.
• •z. Elevated serum fasting clinical chemistry values or complete blood count (CBC) values designated clinically significant by the Investigator and/or medically qualified Sub-Investigator.
• •aa. Screening hemoglobin levels less than 115 g/L or hematocrit less than 0.32 L/L.
• •bb. Participation in another clinical trial involving the administration of an investigational drug or marketed drug or device within the last 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
• •cc. Use of liver enzyme inducers on a regular basis and sex steroid hormone treatments (see Section 8.3 for list of exclusionary medications).
• •dd. Use of monthly injectable contraceptives, unless suspended 2 months before initiation of the treatment. Use of Depo-Provera® \[depot medroxyprogesterone acetate\] unless suspended 9 months before treatment.
• •ee. Current use of implanted hormonal contraceptives, including Mirena® \[progestin containing intrauterine system\], Jadelle®, Norplant®, Implanon® or Nexplanon (if now available in the USA).\*\*
• •ff. Known HIV, Hepatitis B or Hepatitis C infection.
• •gg. History of frequent vaginal infections in the opinion of the Investigator.
• •hh. Known hypersensitivity or prior adverse reaction to itraconazole, or to any of the other azoles or to rifampin, or to any of the rifamycins.
• •(\*Women using non-hormonal intrauterine devices are permitted to enroll in the study.) (\*\*Participants using any of the implanted hormonal methods who request removal for reasons unrelated to the purpose of enrollment in this study may be considered for participation.)