Healthy WomenPhase 2NCT03432416
Study of Efficacy, Cycle Control, and Safety of a NES-E2 Contraceptive Vaginal Ring
A Phase 2 study testing NES-E2 CVR in people with Healthy Women and Female Contraception, run by Premier Research at 11 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Women, Female Contraception
- What is being tested?
- NES-E2 CVR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 385 participants
- Where
- 11 sitesUnited States
- Study dates
- 12 Feb 2018to 14 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Good general overall health with no chronic medical conditions that result in periodic exacerbations requiring significant medical care.
- Age 18-35 years, inclusive, at the enrollment visit. (Note: subjects must be at least 18 years of age to provide consent.)
- Have a regular menstrual cycle 21-35 days in duration when not using hormonal contraception
- Have an intact uterus and at least one ovary.
- 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.)
- 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.
Show all 12Show fewer
- Have a negative pregnancy test at the enrollment visit.
- 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.)
- 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.
- Understand and sign an IRB-approved informed consent form prior to screening activities (including fasting blood draws).
- BMI ≤ 35 kg/m2 and not having previously undergone bariatric surgery.
- 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.
Who cannot join
- Planning pregnancy during study participation through the end of treatment visit.
- Within 30 days post-partum, currently breast-feeding, or has not had a spontaneous menses.
- Post-abortal and has not had a spontaneous menses.
- Abnormal genital bleeding.
- 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.
- Not living in the catchment area of the study site.
Show all 43Show fewer
- Known hypersensitivity to progestins or estrogens.
- Contraindications to combined estrogen-progestin contraceptive use including:
- Thrombophlebitis or thromboembolic disorders.
- Personal history of deep vein 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.
- History of thrombosis or embolism OR any other personal or family history which in the opinion of the investigator suggests increased risk.
- History of stroke.
- Known history of any of the following genetic mutations: Factor V Leiden mutation, prothrombin mutation, antithrombin deficiency, or other clinically significant thrombophilia.
- Known or suspected carcinoma of the breast.
- Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasm.
- History of cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use.
- History of hepatic adenomas or carcinomas.
- Known or suspected pregnancy.
- 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.
- History of retinal vascular lesions, unexplained partial or complete loss of vision.
- History of headaches with focal neurological symptoms (e.g., migraines with auras).
- Impaired mobility (e.g. wheelchair bound, bed-ridden) that, in the opinion of the investigator, places the woman at increased risk of thrombosis.
- 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.
- 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.
- Known benign or malignant liver tumors, renal disease or active liver disease.
- Invasive cancer (past history of any carcinoma or sarcoma, except non-melanoma skin cancer).
- Current or past medically diagnosed severe depression, which, in the opinion of the investigator, could be exacerbated by use of a hormonal contraceptive.
- 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.
- Elevated fasting clinical chemistry values or complete blood count (CBC) values designated clinically significant by the investigator or medically qualified sub-investigator.
- Uncontrolled thyroid disease.
- Known impaired hypothalamic-pituitary-adrenal axis.
- Known hypersensitivity to silicone rubber.
- History of toxic shock syndrome.
- Vaginal anatomic abnormality such as cystocele or rectocele that would preclude correct use of a vaginal ring.
- Planning major surgery during study participation.
- Severe current constipation.
- Use of liver enzyme inducers or inhibitors on a regular basis.
- Known HIV infection.
- Use of any medications, including antibiotics that can significantly interfere with the metabolism of hormonal contraceptives.
- Have an anticipated need for regular condom use, defined as use of at least one condom per month after enrollment.
- 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.
- Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of Colorado Denver
Aurora, Colorado, 80045
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
University of Cincinnati
Cincinnati, Ohio, 45267
Essential Access Health
Los Angeles, California, 30010
Bellevue Hospital Center
New York, New York, 10016
Columbia University
New York, New York, 10032
Eastern Virginia Medical School
Norfolk, Virginia, 23507
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, 19104
Oregon Health Science University
Portland, Oregon, 97239
University of California, Davis
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84132
About this study
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).
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).
Read the 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.
- Conditions
- Healthy Women, Female Contraception
- Being tested
- NES-E2 CVR
- Keywords
- Healthy Women, Female Contraception, Vaginal Ring, Contraceptive Vaginal Ring
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NES-E2 CVRDrug
NES-E2 CVR
| Study group | Role | What they receive |
|---|---|---|
| Regimen 1: Continuous Usage | Experimental | Contraceptive vaginal ring delivering a daily dose of Nestorone® and estradiol (NES-E2 CVR) worn continuously for 91 days. Receives: Drug: NES-E2 CVR |
| Regimen 2: Cyclical Usage | Experimental | 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). Receives: Drug: NES-E2 CVR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pregnancy Rate
Measured: 1 year
Secondary outcomes (27)
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.
Measured: 1 year
Difference in bleeding patterns for continuous vs cyclic use using a bleeding diary.
Measured: 1 year
Incidence of adverse events, including serious adverse events
Measured: 1 year
Summary of number of bleeding and spotting days per 30- and 90- day intervals using a bleeding diary.
Measured: Every 30 and 90 days up to a total of 1 year
Summary of cyclic versus continuous use adverse events.
Measured: 1 year
Summary of acceptability questionnaires.
Measured: 1 year
Changes in complete blood count (CBC) labs from study entry (baseline)
Measured: 1 year
Changes in fasting sodium from study entry (baseline)
Measured: 1 year
Changes in fasting potassium from study entry (baseline)
Measured: 1 year
Changes in fasting chloride from study entry (baseline)
Measured: 1 year
Changes in fasting HCO3/CO2 from study entry (baseline)
Measured: 1 year
Changes in fasting glucose from study entry (baseline)
Measured: 1 year
Changes in fasting creatinine from study entry (baseline)
Measured: 1 year
Changes in fasting blood urea nitrogen (BUN) from study entry (baseline)
Measured: 1 year
Changes in fasting calcium from study entry (baseline)
Measured: 1 year
Changes in fasting Gamma-glutamyl transferase or Gamma-glutamyl transpeptidase (GGTP) from study entry (baseline)
Measured: 1 year
Changes in fasting protein from study entry (baseline)
Measured: 1 year
Changes in fasting albumin from study entry (baseline)
Measured: 1 year
Changes in fasting total bilirubin from study entry (baseline)
Measured: 1 year
Changes in fasting direct bilirubin from study entry (baseline)
Measured: 1 year
Changes in fasting alkaline phosphatase (ALPH) from study entry (baseline)
Measured: 1 year
Changes in fasting Alanine Aminotransferase (ALT) from study entry (baseline)
Measured: 1 year
Changes in fasting Aspartate Aminotransferase (AST) from study entry (baseline)
Measured: 1 year
Changes in total cholesterol from study entry (baseline)
Measured: 1 year
Changes in triglycerides from study entry (baseline)
Measured: 1 year
Changes in high-density lipoprotein (HDL) from study entry (baseline)
Measured: 1 year
Changes in low-density lipoprotein (LDL) from study entry (baseline)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2018
- Study start12 Feb 2018
- Primary completion28 Aug 2021
- Study completion14 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Healthy WomenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 385 participants (actual)
Sponsor and investigators
- Lead sponsor
- Premier Research
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Population Council
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03432416
- Sponsor's protocol ID
- CCN012B
- Status last verified
- Oct 2025
- First submitted
- 22 Jan 2018
- Last updated
- 31 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
Speidel JJ, Harper CC, Shields WC. The potential of long-acting reversible contraception to decrease unintended pregnancy. Contraception. 2008 Sep;78(3):197-200. doi: 10.1016/j.contraception.2008.06.001. Epub 2008 Jul 9. No abstract available.
PubMed 18692608Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health. 2006 Jun;38(2):90-6. doi: 10.1363/psrh.38.090.06.
PubMed 16772190Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. doi: 10.1093/humupd/dmi046. Epub 2005 Nov 16.
PubMed 16291771Sitruk-Ware R. Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7. doi: 10.1016/j.maturitas.2008.11.011.
PubMed 19434887Heikinheimo O, Ranta S, Moo-Young A, Lahteenmaki P, Gordon K. Parenteral administration of progestin Nestorone to lactating cynomolgus monkeys: an ideal hormonal contraceptive at lactation? Hum Reprod. 1999 Aug;14(8):1993-7. doi: 10.1093/humrep/14.8.1993.
PubMed 10438416Heikinheimo O, Noe G, Haukkamaa M, Lahteenmaki P. The progestin ST 1435--rapid metabolism in man. Contraception. 1994 Sep;50(3):275-89. doi: 10.1016/0010-7824(94)90073-6.
PubMed 7805378Kumar N, Koide SS, Tsong Y, Sundaram K. Nestorone: a progestin with a unique pharmacological profile. Steroids. 2000 Oct-Nov;65(10-11):629-36. doi: 10.1016/s0039-128x(00)00119-7.
PubMed 11108869Kumar N, Fagart J, Liere P, Mitchell SJ, Knibb AR, Petit-Topin I, Rame M, El-Etr M, Schumacher M, Lambert JJ, Rafestin-Oblin ME, Sitruk-Ware R. Nestorone(R) as a Novel Progestin for Nonoral Contraception: Structure-Activity Relationships and Brain Metabolism Studies. Endocrinology. 2017 Jan 1;158(1):170-182. doi: 10.1210/en.2016-1426.
PubMed 27824503Haukkamaa M, Laurikka-Routti M, Heikinheimo O, Moo-Young A. Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study. Contraception. 1992 Jan;45(1):49-55. doi: 10.1016/0010-7824(92)90140-o.
PubMed 1591921Fraser IS, Weisberg E, Brache V, Alvarez F, Massai R, Mishell DR Jr, Apter D, Gale J, Tsong YY, Sivin I. Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen. Contraception. 2005 Jul;72(1):40-5. doi: 10.1016/j.contraception.2004.12.015.
PubMed 15964291Sivin I, Mishell DR Jr, Alvarez F, Brache V, Elomaa K, Lahteenmaki P, Massai R, Miranda P, Croxatto H, Dean C, Small M, Nash H, Jackanicz TM. Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial. Contraception. 2005 Feb;71(2):122-9. doi: 10.1016/j.contraception.2004.08.010.
PubMed 15707562Weisberg E, Brache V, Alvarez F, Massai R, Mishell DR Jr, Apter D, Gale J, Sivin I, Tsong YY, Fraser IS. Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen. Contraception. 2005 Jul;72(1):46-52. doi: 10.1016/j.contraception.2004.12.014.
PubMed 15964292Rad M, Kluft C, Menard J, Burggraaf J, de Kam ML, Meijer P, Sivin I, Sitruk-Ware RL. Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables. Am J Obstet Gynecol. 2006 Jul;195(1):72-7. doi: 10.1016/j.ajog.2005.12.007. Epub 2006 Mar 20.
PubMed 16545330Kluft C, Meijer P, LaGuardia KD, Fisher AC. Comparison of a transdermal contraceptive patch vs. oral contraceptives on hemostasis variables. Contraception. 2008 Feb;77(2):77-83. doi: 10.1016/j.contraception.2007.10.004. Epub 2008 Jan 11.
PubMed 18226669
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT03432416
- Acronym / sponsor ID
- CCN012B
- Conditions
- Healthy Women, Female Contraception
- Keywords
- Healthy Women, Female Contraception, Vaginal Ring, Contraceptive Vaginal Ring
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 385 participants (actual)
- Lead sponsor
- Premier ResearchUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Population Council
- Study start
- 12 Feb 2018 (actual)
- Primary completion
- 28 Aug 2021 (actual)
- Study completion
- 14 Dec 2021 (actual)
- First posted
- 14 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regimen 1: Continuous Usage | Experimental | Drug: NES-E2 CVRContraceptive vaginal ring delivering a daily dose of Nestorone® and estradiol (NES-E2 CVR) worn continuously for 91 days. |
| Regimen 2: Cyclical Usage | Experimental | Drug: NES-E2 CVRContraceptive 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). |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Good general overall health with no chronic medical conditions that result in periodic exacerbations requiring significant medical care.
- Age 18-35 years, inclusive, at the enrollment visit. (Note: subjects must be at least 18 years of age to provide consent.)
- Have a regular menstrual cycle 21-35 days in duration when not using hormonal contraception
- Have an intact uterus and at least one ovary.
- 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.)
Key exclusion criteria (43 listed)
- Planning pregnancy during study participation through the end of treatment visit.
- Within 30 days post-partum, currently breast-feeding, or has not had a spontaneous menses.
- Post-abortal and has not had a spontaneous menses.
- Abnormal genital bleeding.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NES-E2 CVRNES-E2 CVR | Drug | Regimen 1: Continuous Usage, Regimen 2: Cyclical Usage |
Primary outcome
Pregnancy Rate
Time frame: 1 year
27 secondary outcomes
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
Difference in bleeding patterns for continuous vs cyclic use using a bleeding diary.
Time frame: 1 year
Incidence of adverse events, including serious adverse events
Time frame: 1 year
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
Summary of cyclic versus continuous use adverse events.
Time frame: 1 year
Summary of acceptability questionnaires.
Time frame: 1 year
Changes in complete blood count (CBC) labs from study entry (baseline)
Time frame: 1 year
Changes in fasting sodium from study entry (baseline)
Time frame: 1 year
Changes in fasting potassium from study entry (baseline)
Time frame: 1 year
Changes in fasting chloride from study entry (baseline)
Time frame: 1 year
Changes in fasting HCO3/CO2 from study entry (baseline)
Time frame: 1 year
Changes in fasting glucose from study entry (baseline)
Time frame: 1 year
Changes in fasting creatinine from study entry (baseline)
Time frame: 1 year
Changes in fasting blood urea nitrogen (BUN) from study entry (baseline)
Time frame: 1 year
Changes in fasting calcium from study entry (baseline)
Time frame: 1 year
Changes in fasting Gamma-glutamyl transferase or Gamma-glutamyl transpeptidase (GGTP) from study entry (baseline)
Time frame: 1 year
Changes in fasting protein from study entry (baseline)
Time frame: 1 year
Changes in fasting albumin from study entry (baseline)
Time frame: 1 year
Changes in fasting total bilirubin from study entry (baseline)
Time frame: 1 year
Changes in fasting direct bilirubin from study entry (baseline)
Time frame: 1 year
Changes in fasting alkaline phosphatase (ALPH) from study entry (baseline)
Time frame: 1 year
Changes in fasting Alanine Aminotransferase (ALT) from study entry (baseline)
Time frame: 1 year
Changes in fasting Aspartate Aminotransferase (AST) from study entry (baseline)
Time frame: 1 year
Changes in total cholesterol from study entry (baseline)
Time frame: 1 year
Changes in triglycerides from study entry (baseline)
Time frame: 1 year
Changes in high-density lipoprotein (HDL) from study entry (baseline)
Time frame: 1 year
Changes in low-density lipoprotein (LDL) from study entry (baseline)
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2025.
- BackgroundDaulaire 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.
- Background: PubMed 18692608Speidel JJ, Harper CC, Shields WC. The potential of long-acting reversible contraception to decrease unintended pregnancy. Contraception. 2008 Sep;78(3):197-200. doi: 10.1016/j.contraception.2008.06.001. Epub 2008 Jul 9. No abstract available.
- Background: PubMed 16772190Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health. 2006 Jun;38(2):90-6. doi: 10.1363/psrh.38.090.06.
- Background: PubMed 16291771Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. doi: 10.1093/humupd/dmi046. Epub 2005 Nov 16.
- Background: PubMed 19434887Sitruk-Ware R. Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7. doi: 10.1016/j.maturitas.2008.11.011.
- Background: PubMed 10438416Heikinheimo O, Ranta S, Moo-Young A, Lahteenmaki P, Gordon K. Parenteral administration of progestin Nestorone to lactating cynomolgus monkeys: an ideal hormonal contraceptive at lactation? Hum Reprod. 1999 Aug;14(8):1993-7. doi: 10.1093/humrep/14.8.1993.
- Background: PubMed 7805378Heikinheimo O, Noe G, Haukkamaa M, Lahteenmaki P. The progestin ST 1435--rapid metabolism in man. Contraception. 1994 Sep;50(3):275-89. doi: 10.1016/0010-7824(94)90073-6.
- Background: PubMed 11108869Kumar N, Koide SS, Tsong Y, Sundaram K. Nestorone: a progestin with a unique pharmacological profile. Steroids. 2000 Oct-Nov;65(10-11):629-36. doi: 10.1016/s0039-128x(00)00119-7.
- Background: PubMed 27824503Kumar N, Fagart J, Liere P, Mitchell SJ, Knibb AR, Petit-Topin I, Rame M, El-Etr M, Schumacher M, Lambert JJ, Rafestin-Oblin ME, Sitruk-Ware R. Nestorone(R) as a Novel Progestin for Nonoral Contraception: Structure-Activity Relationships and Brain Metabolism Studies. Endocrinology. 2017 Jan 1;158(1):170-182. doi: 10.1210/en.2016-1426.
- Background: PubMed 1591921Haukkamaa M, Laurikka-Routti M, Heikinheimo O, Moo-Young A. Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study. Contraception. 1992 Jan;45(1):49-55. doi: 10.1016/0010-7824(92)90140-o.
- Background: PubMed 15964291Fraser IS, Weisberg E, Brache V, Alvarez F, Massai R, Mishell DR Jr, Apter D, Gale J, Tsong YY, Sivin I. Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen. Contraception. 2005 Jul;72(1):40-5. doi: 10.1016/j.contraception.2004.12.015.
- Background: PubMed 15707562Sivin I, Mishell DR Jr, Alvarez F, Brache V, Elomaa K, Lahteenmaki P, Massai R, Miranda P, Croxatto H, Dean C, Small M, Nash H, Jackanicz TM. Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial. Contraception. 2005 Feb;71(2):122-9. doi: 10.1016/j.contraception.2004.08.010.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NES-E2 CVR in people with Healthy Women and Female Contraception, run by Premier Research at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pregnancy Rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03432416, which also lists 32 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2025.