A multicenter, open-label study on the efficacy, cycle control and safety of a contraceptivevaginal ring delivering a daily dose of 150 µg of Nestorone(R) and 15 µg of ethinyl estradiol (150/15 NES/EE CVR)

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 2200

Inclusion Criteria

a. Healthy women, aged 18-<40 years at the enrollment visit who wish to use a combined hormonal contraceptive
b. Women not intending to become pregnant before December 31, 2008
c. Intact uterus and both ovaries.
d. Prior history of regular menstrual cycles that usually occur every 28 ± 7 days when not using hormonal contraception; if postpartum or postabortal, history of regular menstrual cycles of 21-35 days in length and resumption of at least one cycle with a cycle length consistent with her past cycles.
e. Sexually active (currently) and willing to discontinue current contraceptive method to participate in the study.
f. 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.
g. Do not meet any of the exclusion criteria.
h. Signed informed consent prior to entry into the trial.
Amd9-EX: i. Completion of 13 cycles in Protocol 300B immediately prior to entry in the
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

a. Known hypersensitivity to estrogens or progestins
b. Known hypersensitivity to silicone rubber.
c. Known or suspected pregnancy.
d. History of infertility of >1.0 year in woman or her male partner.
e. History of vasectomy or sterility in male partner; tubal ligation (sterilization) in women.
f. Undiagnosed abnormal genital bleeding.
g. Undiagnosed vaginal discharge or vaginal lesions or abnormalities.
h. History of pelvic inflammatory disease since last pregnancy episode.
i. History of toxic shock syndrome.
j. 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 it 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 if further evaluated with colposcopy and, as needed, biopsy with endocervical curettage.
· Women may participate if colposcopy findings are negative provided there is appropriate follow up in accordance with local standards of care;
· Women whose colposcopy results indicate need for biopsy may participate as long as biopsy results indicate there is no lesion with a severity > CIN I and endocervical curettage results are negative.
k. Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a vaginal ring.
l. Women planning to undergo major surgery.
m. 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 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.
n. Breastfeeding.
o. Current or past thrombophlebitis or thromboembolic disorders.
p. 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.
q. Cerebrovascular or cardiovascular disease.
r. History of retinal vascular lesions, unexplained partial or complete loss of vision.
s. Known or suspected carcinoma of the breast.
t. Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia.
u. Past history of any other carcinoma unless in remission for more than 5 years.
v. Current or history of medically diagnosed severe depression, which, in the opinions of the investigator, could be exacerbated by use of a hormonal contraceptive.
w. Headaches with focal neurological symptoms.
x. Severe constipation.
y. History of cholestatic jaundice of pregnancy or jaundice with prior steroid use.
z. Benign or malignant liver tumors; active liver disease.
aa. Diastolic blood pressure (BP) >85 mm Hg and/or systolic BP >135 mm Hg after 5-10 minutes rest.
bb. Known or suspected alcoholism or drug abuse.
cc. Abnormal serum chemistry values according to the physician’s judgment.
dd.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To evaluate the cycle control, bleeding patterns, side effects, and acceptability of a 21-day continuous use regimen of the CVR, followed by one week off per cycle. ;Primary end point(s): The primary efficacy endpoint is the Pearl Index per 100 woman years for women <= 35 years. ;Main Objective: To evaluate one-year data on the contraceptive efficacy and safety of the 150/15 NES/EE CVR as the basis for regulatory approvals of this CVR as a new delivery system for contraception.

Secondary Outcome Measures

Name	Time	Method

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