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Study of Efficacy, Cycle Control, and Safety of a NES-E2 Contraceptive Vaginal Ring

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03432416
Recruitment Status : Recruiting
First Posted : February 14, 2018
Last Update Posted : May 20, 2019
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Population Council
Information provided by (Responsible Party):
Health Decisions

Brief Summary:
This will be a multi-site, open-label, randomized clinical trial. The investigators will randomize 300 eligible participants in a 1:1 ratio to two different treatment regimens that are to be followed when using a contraceptive vaginal ring delivering a daily dose of Nestorone® and estradiol (NES-E2 CVR).

Condition or disease Intervention/treatment Phase
Healthy Women Female Contraception Drug: NES-E2 CVR Phase 2

Detailed Description:

The total duration of the study for each participant is expected to be approximately 13.5-15.5 months: including screening and enrollment (up to 8 weeks), 12 months of participation, and a post-removal follow up period removal of at least 17 days. After enrollment, subject visits occur at day 31, 92, 183, 274, and 364 with telephone calls at day 60, 120, 150, 210, 240, 300, and 330. Subjects will use a home pregnancy test 17 days post-removal of the ring and will call the site report the result and for safety follow-up. Another phone call will be required after that if the subject chooses not to being a hormonal contraceptive; this call will occur at the time of the subject's first spontaneous menses.

Subject recruitment is expected to begin Q1 (in the first quarter of) 2018 and is planned to continue through Q1 2019. However, if the enrollment rate declines, the enrollment period may be extended beyond this date. If this enrollment timeline is met, all subjects should finish active treatment by approximately the end of Q1 2020. The end of the study will occur when the last subject to be enrolled has completed her post-removal telephone call(s).

Preliminary results of the study are expected to be available Q3 of 2020 based on the current study plan.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Multicenter, Open-label Randomized Study on the Efficacy, Cycle Control and Safety of a Contraceptive Vaginal Ring Delivering a Daily Dose of Nestorone® and Estradiol (NES-E2 CVR).
Actual Study Start Date : February 12, 2018
Estimated Primary Completion Date : March 20, 2020
Estimated Study Completion Date : June 20, 2020

Arm Intervention/treatment
Experimental: Regimen 1: Continuous Usage
Contraceptive vaginal ring delivering a daily dose of Nestorone® and estradiol (NES-E2 CVR) worn continuously for 91 days.
Drug: NES-E2 CVR
NES-E2 CVR

Experimental: Regimen 2: Cyclical Usage
Contraceptive vaginal ring delivering a daily dose of Nestorone® and estradiol (NES-E2 CVR) worn for 91 days, but is removed for 2 days each month (days 29-30, 59-60, and 90-91).
Drug: NES-E2 CVR
NES-E2 CVR




Primary Outcome Measures :
  1. Pregnancy Rate [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Change in subjects' bleeding patterns for continuous vs cyclic use as compared to reported baseline bleeding patterns when the subjects were not on hormonal contraception using a bleeding questionnaire. [ Time Frame: 1 year ]
  2. Difference in bleeding patterns for continuous vs cyclic use using a bleeding diary. [ Time Frame: 1 year ]
  3. Incidence of adverse events, including serious adverse events [ Time Frame: 1 year ]
  4. Summary of number of bleeding and spotting days per 30- and 90- day intervals using a bleeding diary. [ Time Frame: Every 30 and 90 days up to a total of 1 year ]
  5. Summary of cyclic versus continuous use adverse events. [ Time Frame: 1 year ]
  6. Summary of acceptability questionnaires. [ Time Frame: 1 year ]
  7. Changes in complete blood count (CBC) labs from study entry (baseline) [ Time Frame: 1 year ]
  8. Changes in fasting sodium from study entry (baseline) [ Time Frame: 1 year ]
  9. Changes in fasting potassium from study entry (baseline) [ Time Frame: 1 year ]
  10. Changes in fasting chloride from study entry (baseline) [ Time Frame: 1 year ]
  11. Changes in fasting HCO3/CO2 from study entry (baseline) [ Time Frame: 1 year ]
  12. Changes in fasting glucose from study entry (baseline) [ Time Frame: 1 year ]
  13. Changes in fasting creatinine from study entry (baseline) [ Time Frame: 1 year ]
  14. Changes in fasting blood urea nitrogen (BUN) from study entry (baseline) [ Time Frame: 1 year ]
  15. Changes in fasting calcium from study entry (baseline) [ Time Frame: 1 year ]
  16. Changes in fasting Gamma-glutamyl transferase or Gamma-glutamyl transpeptidase (GGTP) from study entry (baseline) [ Time Frame: 1 year ]
  17. Changes in fasting protein from study entry (baseline) [ Time Frame: 1 year ]
  18. Changes in fasting albumin from study entry (baseline) [ Time Frame: 1 year ]
  19. Changes in fasting total bilirubin from study entry (baseline) [ Time Frame: 1 year ]
  20. Changes in fasting direct bilirubin from study entry (baseline) [ Time Frame: 1 year ]
  21. Changes in fasting alkaline phosphatase (ALPH) from study entry (baseline) [ Time Frame: 1 year ]
  22. Changes in fasting Alanine Aminotransferase (ALT) from study entry (baseline) [ Time Frame: 1 year ]
  23. Changes in fasting Aspartate Aminotransferase (AST) from study entry (baseline) [ Time Frame: 1 year ]
  24. Changes in total cholesterol from study entry (baseline) [ Time Frame: 1 year ]
  25. Changes in triglycerides from study entry (baseline) [ Time Frame: 1 year ]
  26. Changes in high-density lipoprotein (HDL) from study entry (baseline) [ Time Frame: 1 year ]
  27. Changes in low-density lipoprotein (LDL) from study entry (baseline) [ Time Frame: 1 year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Good general overall health with no chronic medical conditions that result in periodic exacerbations requiring significant medical care.
  2. Age 18-35 years, inclusive, at the enrollment visit. (Note: subjects must be at least 18 years of age to provide consent.)
  3. Have a regular menstrual cycle 21-35 days in duration when not using hormonal contraception
  4. Have an intact uterus and at least one ovary.
  5. Consistent use of effective contraception during the preceding cycle with no unprotected intercourse since last use (NOTE: women who use oral, transdermal, vaginal, or implantable hormonal contraceptives in the preceding cycle must have discontinued hormone use at least 4 days prior to start of treatment and must not have had unprotected intercourse since discontinuing the method. Copper IUD or Levonorgestrel releasing IUD users must have discontinued IUD use at least 4 days prior to start of treatment and have experienced a spontaneous menses following IUD removal.)
  6. No use of injectable contraceptives (e.g. depomedroxyprogesterone acetate) during the 10 months prior to screening unless the subject has returned to normal menses (two consecutive menses) since last injection.
  7. Have a negative pregnancy test at the enrollment visit.
  8. Have a diastolic blood pressure (BP) <90 mm Hg and systolic BP <140 mm Hg after 5 minutes rest in sitting position at the admission visit (below hypertension stage 2). (Note: History of hypertension stage 2 or higher, even if controlled with treatment, is exclusionary.)
  9. Willing to abstain from use of non-water based (including silicone based) vaginal lubricants during the study that could adversely affect the ring, causing it to expand.
  10. Understand and sign an IRB-approved informed consent form prior to screening activities (including fasting blood draws).
  11. BMI ≤ 35 kg/m2 and not having previously undergone bariatric surgery.
  12. Planning to have at least one act of heterosexual intercourse without the use of another contraceptive method each month during study participation until end of treatment and at risk for pregnancy.

Exclusion Criteria:

  1. Planning pregnancy during study participation through the end of treatment visit.
  2. Within 30 days post-partum, currently breast-feeding, or has not had a spontaneous menses.
  3. Post-abortal and has not had a spontaneous menses.
  4. Abnormal genital bleeding.
  5. Participating in another clinical trial involving an investigational product within the last 30 days (prior to screening) or planning to participate in another clinical trial during this study.
  6. Not living in the catchment area of the study site.
  7. Known hypersensitivity to progestins or estrogens.
  8. Contraindications to combined estrogen-progestin contraceptive use including:

    1. Thrombophlebitis or thromboembolic disorders.
    2. Personal history of deep vein thrombophlebitis or thromboembolic disorders.
    3. History of venous thrombosis or embolism in a first-degree relative <55 years of age suggesting a familial defect in the blood coagulation system.
    4. History of thrombosis or embolism OR any other personal or family history which in the opinion of the investigator suggests increased risk.
    5. History of stroke.
    6. Known history of any of the following genetic mutations: Factor V Leiden mutation, prothrombin mutation, antithrombin deficiency, or other clinically significant thrombophilia.
    7. Known or suspected carcinoma of the breast.
    8. Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasm.
    9. History of cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use.
    10. History of hepatic adenomas or carcinomas.
    11. Known or suspected pregnancy.
    12. Smoking in women who are or will be 35 years during the course of the trial; women <35 years who smoke 15 cigarettes or more per day must be evaluated by the investigator for inclusion based on risk factors that would increase their risk for cardiovascular disease (CVD) and thromboembolism, e.g. lipid levels, glucose level, BP, BMI, family history of CVD at a young age. Individuals who use other forms of tobacco should be evaluated similarly by the investigator for inclusion based on the amount of tobacco use and their risk factors.
    13. History of retinal vascular lesions, unexplained partial or complete loss of vision.
    14. History of headaches with focal neurological symptoms (e.g., migraines with auras).
    15. Impaired mobility (e.g. wheelchair bound, bed-ridden) that, in the opinion of the investigator, places the woman at increased risk of thrombosis.
  9. Unevaluated vaginal discharge or vaginal lesions. Subjects diagnosed at screening with a chlamydia or gonococcal infection may be included in the trial following treatment completion; partner treatment is also recommended. Subjects with yeast, trichomoniasis, or bacterial vaginosis infection requiring treatment may be enrolled after treatment completion. Investigators should determine if subjects are at an elevated risk for reinfection, e.g. multiple sex partners, untreated partner, and whether such subjects can be included. Women with a history of genital herpes can be included if outbreaks are infrequent.
  10. Have a known clinically significant Pap test abnormality, as managed by normal standard of care guidelines, that would require repeat evaluation or treatment during study participation based on the initial Pap findings.
  11. Known benign or malignant liver tumors, renal disease or active liver disease.
  12. Invasive cancer (past history of any carcinoma or sarcoma, except non-melanoma skin cancer).
  13. Current or past medically diagnosed severe depression, which, in the opinion of the investigator, could be exacerbated by use of a hormonal contraceptive.
  14. Known or suspected current alcohol dependence, chronic marijuana use, or any illicit drug use that may affect metabolism/transformation of study product and/or study treatment compliance. A chronic marijuana user is defined as someone who uses marijuana 4 or more times per week for study purposes.
  15. Elevated fasting clinical chemistry values or complete blood count (CBC) values designated clinically significant by the investigator or medically qualified sub-investigator.
  16. Uncontrolled thyroid disease.
  17. Known impaired hypothalamic-pituitary-adrenal axis.
  18. Known hypersensitivity to silicone rubber.
  19. History of toxic shock syndrome.
  20. Vaginal anatomic abnormality such as cystocele or rectocele that would preclude correct use of a vaginal ring.
  21. Planning major surgery during study participation.
  22. Severe current constipation.
  23. Use of liver enzyme inducers or inhibitors on a regular basis.
  24. Known HIV infection.
  25. Use of any medications, including antibiotics that can significantly interfere with the metabolism of hormonal contraceptives.
  26. Have an anticipated need for regular condom use, defined as use of at least one condom per month after enrollment.
  27. Have issues or concerns (in the judgment of the investigator) that may compromise the safety of the subject or confound the reliability of compliance and information acquired in this study.
  28. Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03432416


Contacts
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Contact: Emily Korhonen 919-967-1111 ext 107 ekorhonen@healthdec.com
Contact: Abbey Townsend 919-967-1111 ext 308 atownsend@healthdec.com

Locations
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United States, California
Essential Access Health Recruiting
Los Angeles, California, United States, 30010
Contact: Kieumai Vo    213-386-5614 ext 4592    KVo@essentialaccess.org   
Contact: Seline Guidotti    213-386-5614 ext 4500    SGuidotti@essentialaccess.org   
Principal Investigator: Anita Nelson         
University of California, Davis Recruiting
Sacramento, California, United States, 95817
Contact: Courtney Overstreet    916-734-6846    cboverstreet@ucdavis.edu   
Contact: Aubrey Blanton    916-734-6846    akblanton@ucdavis.edu   
Principal Investigator: Mitchell Creinin         
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Lisa Powers    303-724-2013    LISA.POWERS@UCDENVER.EDU   
Contact: Rebecca Seale    303-724-2013    REBECCA.SEALE@UCDENVER.EDU   
Principal Investigator: Stephanie Teal         
United States, Maryland
Johns Hopkins Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224
Contact: Katrina Thaler    410-550-8506    kstouff3@jhmi.edu   
Contact: Lauren Beal    410-550-4825    lbeal2@jhu.edu   
Principal Investigator: Anne Burke         
United States, New York
Bellevue Hospital Center Recruiting
New York, New York, United States, 10016
Contact: Anna Davis    212-263-6253    anna.davis@nyulangone.org   
Principal Investigator: Treasure Walker         
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Molly Morgan    212-305-0947    mjm2331@cumc.columbia.edu   
Contact: Yessica Vanterpool    212-305-8031    mjm2331@cumc.columbia.edu   
Principal Investigator: Carolyn Westhoff         
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Deborah Boerschig    513-584-4100    BOERSCDA@UCMAIL.UC.EDU   
Contact: Tiffany Rupert    513-584-4100    rupertts@ucmail.uc.edu   
Principal Investigator: Michael Thomas         
United States, Oregon
Oregon Health Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Ariela Schnyer    503-494-3173    schnyer@ohsu.edu   
Contact: Alison Edelman    503-494-5949    edelmana@ohsu.edu   
Principal Investigator: Jeffrey Jensen         
United States, Pennsylvania
University of Pennsylvania School of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Andrea Morley    215-615-4202    Andrea.morley@uphs.upenn.edu   
Contact: Kieran Alessi    215-615-3664    Kieran.Alessi@uphs.upenn.edu   
Principal Investigator: Kurt Barnhart         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Jasmin Alcantra    801-213-3796    jasmin.alcantara@hsc.utah.edu   
Contact: Amy Orr    801-213-2774    amy.orr@hsc.utah.edu   
Principal Investigator: David Turok         
United States, Virginia
Eastern Virginia Medical School Recruiting
Norfolk, Virginia, United States, 23507
Contact: Jackie Rocccazella    757-446-7161    roccazj@evms.edu   
Principal Investigator: David Archer         
Sponsors and Collaborators
Health Decisions
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Population Council
Publications:
Daulaire N, Leidl P, Mackin L et al., Promises to Keep: The Toll of Unintended Pregnancies on Women's Lives in the Developing World. Washington, DC: Global Health Council; 2002; 11.
Marty JP, James M, Hajo N, Wepierre J Percutaneous absorption of oestradiol and progesterone: Pharmacokinetic studies. In P Mauvais-Jarvis, CFH Vickers, J Wepierre (Eds), Percutaneous absorption of steroids. London: Academic Press Inc. (London) Ltd. 1980.
Protocol 330. Clinical Study Report on File. Population Council, New York, NY.

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Responsible Party: Health Decisions
ClinicalTrials.gov Identifier: NCT03432416    
Other Study ID Numbers: CCN012B
First Posted: February 14, 2018    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Health Decisions:
Healthy Women
Female Contraception
Vaginal Ring
Contraceptive Vaginal Ring