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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00263341




Registration number
NCT00263341
Ethics application status
Date submitted
6/12/2005
Date registered
8/12/2005
Date last updated
6/10/2017

Titles & IDs
Public title
Safety and Efficacy of a Contraceptive Vaginal Ring Delivering Nestorone® and Ethinyl Estradiol
Scientific title
A Multicenter, Open-label Study on the Efficacy, Cycle Control and Safety of a Contraceptive Vaginal Ring Delivering a Daily Dose of 150 ug of Nestorone® and 15 ug of Ethinyl Estradiol
Secondary ID [1] 0 0
Protocol 300
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Contraception 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - NES/EE CVR

Other interventions: NES/EE CVR
This is a Phase 3, multicenter, open-label study of a 21/7-day regimen of the 150/15 NES/EE CVR, in healthy women followed on an outpatient basis up to one year (13 cycles) of treatment over one year. Because of the stop treatment date of December 31, 2008 for all participants, women enrolling or re-enrolling in 2008 may not complete a full 13 cycles of treatment. Subjects may also participate in a 6 month follow-up period after the 300B study. The ring is designed to last for 12 months.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Efficacy
Timepoint [1] 0 0
At all visits
Primary outcome [2] 0 0
Safety
Timepoint [2] 0 0
At all visits

Eligibility
Key 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
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key 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).

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2014
Sample size
Target
Accrual to date
Final
1135
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
FPA Health - Ashfield
Recruitment postcode(s) [1] 0 0
- Ashfield
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Chile
State/province [6] 0 0
Santiago
Country [7] 0 0
Dominican Republic
State/province [7] 0 0
Santo Domingo
Country [8] 0 0
Finland
State/province [8] 0 0
Helsinki
Country [9] 0 0
Hungary
State/province [9] 0 0
Szeged
Country [10] 0 0
Sweden
State/province [10] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Other
Name
Population Council
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
United States Agency for International Development (USAID)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
World Health Organization
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this 1-year study is to evaluate the efficacy and safety of a new contraceptive vaginal ring (CVR) delivering low doses of Nestorone (NES), a new, nonandrogenic progestin, and ethinyl estradiol (EE), an estrogen used in oral contraceptives. The CVR, which is made of silicone rubber, is designed to be used for 1 year (13 menstrual cycles) before replacement is required.
Trial website
https://clinicaltrials.gov/study/NCT00263341
Trial related presentations / publications
Vieira CS, Fraser IS, Plagianos MG, Burke AE, Westhoff CL, Jensen J, Brache V, Bahamondes L, Merkatz R, Sitruk-Ware R, Blithe DL. Bleeding profile associated with 1-year use of the segesterone acetate/ethinyl estradiol contraceptive vaginal system: pooled analysis from Phase 3 trials. Contraception. 2019 Dec;100(6):438-444. doi: 10.1016/j.contraception.2019.07.145. Epub 2019 Aug 6.
Archer DF, Merkatz RB, Bahamondes L, Westhoff CL, Darney P, Apter D, Jensen JT, Brache V, Nelson AL, Banks E, Bartfai G, Portman DJ, Plagianos M, Dart C, Kumar N, Creasy GW, Sitruk-Ware R, Blithe DL. Efficacy of the 1-year (13-cycle) segesterone acetate and ethinylestradiol contraceptive vaginal system: results of two multicentre, open-label, single-arm, phase 3 trials. Lancet Glob Health. 2019 Aug;7(8):e1054-e1064. doi: 10.1016/S2214-109X(19)30265-7. Epub 2019 Jun 20.
Stifani BM, Plagianos M, Vieira CS, Merkatz RB. Factors associated with nonadherence to instructions for using the Nestorone(R)/ethinyl estradiol contraceptive vaginal ring. Contraception. 2018 May;97(5):415-421. doi: 10.1016/j.contraception.2017.12.011. Epub 2017 Dec 18.
Huang Y, Merkatz RB, Hillier SL, Roberts K, Blithe DL, Sitruk-Ware R, Creinin MD. Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation. PLoS One. 2015 Aug 12;10(8):e0134460. doi: 10.1371/journal.pone.0134460. eCollection 2015.
Merkatz RB, Plagianos M, Hoskin E, Cooney M, Hewett PC, Mensch BS. Acceptability of the Nestorone(R)/ethinyl estradiol contraceptive vaginal ring: development of a model; implications for introduction. Contraception. 2014 Nov;90(5):514-21. doi: 10.1016/j.contraception.2014.05.015. Epub 2014 Jun 2.
Public notes

Contacts
Principal investigator
Name 0 0
Ruth Merkatz, Ph.D.
Address 0 0
Population Council
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00263341