Safety and Efficacy of a Contraceptive Vaginal Ring Delivering Nestorone® and Ethinyl Estradiol

NCT00263341 | Completed Phase 3

• 1 other identifier: Protocol 300
• Study Type: interventional
• Target: 1,135
• Locations: 8 countries
• Sites: 12

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.

Conditions

Contraception

Keywords

Contraceptive agents; Female contraception; Progestins

Outcome Measures

Primary Outcomes (2)

• Efficacy

  Primary endpoint: The Pearl Index for women 35 years of age derived from using all cycles for which back up contraception is not used will be the primary efficacy endpoint. This index will be calculated for the women participating in Protocol 300 B and will then be pooled with data from women 35 years who participate in 300 A (CCN006).

  At all visits

• Safety

  Each subject's health status will be monitored carefully throughout the trial. Baseline data collected at the screening visit will consist of the medical and gynecologic history and physical examination findings including breast and pelvic exam (to include Pap test and STI screening for chlamydia and gonorrhea). These assessments will be repeated at the 6th cycle visit (with the exception of the Pap, and STI screening). Baseline data obtained from clinical chemistries and a CBC will be used to monitor liver and renal function, lipid levels and hematologic status.

  At all visits

Interventions

NES/EE CVR COMBINATION_PRODUCT

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.

Also known as: Nestorone (segesterone acetate) Ethinylestradiol Contraceptive Vaginal Ring

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Signed informed consent prior to entry into the trial.
• \[For pharmacokinetics study only; 39 subjects already recruited\]
• \- Willing to undergo frequent blooding sampling
• 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.

Sponsors & Collaborators

• Population Council: lead
• United States Agency for International Development (USAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• World Health Organization: collaborator

Study Sites (12)

Women and Children's Hospital, LAC/USC Medical Center

Los Angeles, California, 90033, United States

Location

University of California, San Francisco General Hospital, Department of Obstetrics & Gynecology

San Francisco, California, 94110, United States

Location

University of Chicago Hospitals

Chicago, Illinois, 60637, United States

Location

Montefiore Medical Center/Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Columbus Center for Women's Heatlh Research

Columbus, Ohio, 43213, United States

Location

FPA Health

Ashfield, Australia

Location

University of Campinas, Department of Obstetrics & Gynecology

São Paulo, Brazil

Location

Instituto Chileno de Medicina Reproductiva

Santiago, Chile

Location

Profamilia

Santo Domingo, Dominican Republic

Location

Family Federation of Finland

Helsinki, Finland

Location

University of Szeged, Department of Obstetrics & Gynecology

Szeged, Hungary

Location

Karolinska Institutet, Department of Woman and Child Health, Division of Obstetrics & Gynecology

Stockholm, SE 17176, Sweden

Location

Related Publications (7)

• Plagianos MG, Ramanadhan S, Merkatz RB, Brache V, Friedland BA, Haddad LB. Risk factors for and outcomes of ring expulsions with a 1-year contraceptive vaginal system. Am J Obstet Gynecol. 2024 May;230(5):548.e1-548.e8. doi: 10.1016/j.ajog.2024.01.020. Epub 2024 Jan 29.

  PMID: 38295968 DERIVED

• Jensen JT, Archer DF, Westhoff CL, Nelson AL, Graham S, Bernick B. Satisfaction with a Segesterone Acetate and Ethinyl Estradiol Contraceptive Vaginal System Among Recent Oral Contraceptive or Hormonal Contraceptive Vaginal Ring Users. J Womens Health (Larchmt). 2023 Jul;32(7):808-815. doi: 10.1089/jwh.2022.0264. Epub 2023 May 29.

  PMID: 37253139 DERIVED

• 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.

  PMID: 31398307 DERIVED

• 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.

  PMID: 31231065 DERIVED

• 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.

  PMID: 29269252 DERIVED

• 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.

  PMID: 26267119 DERIVED

• 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.

  PMID: 24993487 DERIVED

MeSH Terms

Interventions

ST 1435; segesterone acetate and ethinyl estradiol vaginal system

Study Officials

• Ruth Merkatz, Ph.D.

  Population Council

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2005
• First Posted: December 8, 2005
• Study Start: December 1, 2005
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 6, 2017

Record last verified: 2017-10

Locations

BR (1); CL (1); DO (1); HU (1); AU (1); FI (1); US (5); SE (1)