A Study to Evaluate the Effect of a Contraceptive Vaginal... | NCT02451826

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1.5 mg tablet LNG after 12 weeks	Active Comparator	CVR delivering 2,500 µg of Ulipristal acetate per day and a single dose of levonorgestrel delivered in a 1.5 mg tablet after 12 weeks of CVR use	Drug: Ulipristal acetate
1.5 mg tablet LNG every 4 weeks	Active Comparator	CVR delivering 2,500 µg of Ulipristal acetate per day and one 1.5 mg tablet levonorgestrel every 4 weeks of CVR use (three times).	Drug: Ulipristal acetate

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ulipristal acetate	Drug	CVR delivering Ulipristal acetate and one tablet levonorgestrel.	1.5 mg tablet LNG after 12 weeks 1.5 mg tablet LNG every 4 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pharmacodynamic efficacy as measured by the effects of a vaginal ring delivering Ulipristal acetate consistently combined with levonorgestrel administration on the endometrium	Endometrial biopsies (EB) will be taken as follows, a.During the follicular phase (between Day 9 and Day 12) of the baseline/control cycle, b. At the end of the 14th week of treatment (14 days after the 12 week LNG administration and end of CVR use), c. During the follicular phase (between Day 9 and Day 12 of the second menstrual cycle after ring removal). Also, endometrial changes will be measured by histological examination, immunohistochemistry, and assessment of proliferation markers (Ki67, Phospho H3 and bcl2).	3 months

Secondary Outcomes

Measure	Description	Time Frame
Safety as measured by number of participants with occurrence of adverse events (AEs) and concomitant medication use	Safety as measured by the assessment of a vaginal ring delivering Ulipristal acetate consistently combined with levonorgestrel administration	3 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Not at risk for pregnancy based on one of the following: a. subject has undergone sterilization; b. subject is monogamous and her male partner has undergone sterilization
Have regular menstrual cycles of 25-35 days duration
Have an intact uterus and both ovaries
Will be able to comply with the protocol
Capable of giving informed consent

Exclusion Criteria:

Women participating in another clinical trial
Women not living in the catchment area of the clinic
Known hypersensitivity to progestins or antiprogestins
Known hypersensitivity to silicone rubber
Any chronic disease
All contraindications to oral contraceptive use, including: a. Thrombophlebitis or thromboembolic disorders; b. Past history of deep vein thrombophlebitis or thromboembolic disorders; c. Past or current cerebrovascular or coronary artery disease; d. Migraine with focal aura; e. Known or suspected carcinoma of the breast; f. Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia; g. Undiagnosed abnormal genital bleeding; h. Cholestatic jaundice of pregnancy or jaundice with prior pill use; i. Hepatic adenomas or carcinomas; j. Known or suspected pregnancy
Desire to get pregnant during the study (through the use of reproductive technology for sterilized women or vasectomy reversal for sterilized partners)
Breastfeeding
Undiagnosed vaginal discharge or vaginal lesions or abnormalities
Women with a current abnormal Pap: In accordance with the Bethesda system of classification: 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 it treatment is indicated.
Known benign or malignant liver tumors; known active liver disease
Cancer (past history of any carcinoma or sarcoma)
Medically diagnosed severe depression currently or in the past
Known or suspected alcoholism or drug abuse
Abnormal serum fasting clinical chemistry values
Women with known abnormal thyroid status
Women with known impaired hypothalamic-pituitary-adrenal reserve
Average diastolic BP > 85 mm or systolic BP >135 mm Hg after 5-10 minutes rest
Body mass index (BMI) > 30.0 (or ≤18)
Smoking in women who will be 35 years during the course of the trial; women < 35 years who smoke greater than 15 cigarettes per day must be evaluated by the PI for inclusion based on risk factors that would increase their risk for CVD and thromboembolism, e.g. lipid levels, glucose level, BP, BMI, family history of CVD at a young age.
Women with severe cystoceles or rectoceles
Use within the past 2 months of any implanted hormonal contraceptives including Mirena [progestin containing intrauterine system (IUS)] or Norplant (subdermal implant delivering LNG). NOTE: Removal of implanted hormonal contraceptives must have been for personal reasons unrelated to the purpose of enrollment in this study.
Current use of a non-hormone containing IUD. NOTE: Removal of an IUD must have been for personal reasons unrelated to the purpose of enrollment in this study.
Use of injectable contraceptives during the previous 3 months (e.g. Cyclofem) or 6 months (e.g. DMPA).
Women who do not have at least two progesterone measurements during the control cycle of ≥10nmol/L will be excluded from further participation in the study (See Section 13.4.1)