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HealthyPhase 2NCT03452111

Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception

A Phase 2 study testing Nestorone + Testosterone Combination Gel in people with Healthy and Men, run by Premier Research at 17 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The long term objective is to develop a gel to be used as a male contraceptive. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Healthy, Men, Male Contraception
What is being tested?
Nestorone + Testosterone Combination Gel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
420 participants
Where
17 sitesin 7 countries
Study dates
25 Oct 2018to 6 Sep 2024
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 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Men who meet all the following criteria will be eligible for enrollment in the trial:
  • Good health as confirmed by medical history, physical examination, and clinical laboratory tests of blood and urine at the time of screening;
  • 18 to 50 years of age, at the enrollment visit;
  • BMI < 33 kg/m2;
  • No history of androgen use in the six months prior to the first screening visit;
  • Agreement to use an effective method of contraception with his female partner (refer to Appendix 11 for acceptable forms of contraception) during the suppression and the first 7 days of the recovery phase and then only use the experimental method during the efficacy phase of the study;
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  • In the opinion of the investigator, the male subject is willing and able to comply with the protocol, understand and sign an informed consent and HIPAA form;
  • The subject is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions and has duly signed the informed consent form (ICF);
  • Sexually active with a female partner (as specified below) with whom he has been in a stable, mutually monogamous relationship for at least 1 year prior to screening and with whom he intends to remain in a relationship for the duration of the study;
  • No known infertility;
  • Normal reproductive state as demonstrated by:
  • Sperm concentration ≥15 million/mL in two semen samples and with no gross abnormalities of sperm motility and morphology on at least one semen sample assessment;
  • Screening Testosterone within the study site's local lab normal reference range for adult men;
  • Willingness to accept a low but unknown risk of conceiving a pregnancy for the duration of the trial.
  • Female participant - Inclusion Criteria
  • Women who meet all the following criteria will be eligible for enrollment in the trial:
  • Good general health with no chronic medical conditions that result in periodic exacerbations which require significant medical care or are known to affect fertility;
  • Aged between 18 and 34 years, inclusive, at the enrollment visit;
  • Have regular menstrual cycles of 21-35 days in duration, per patient report, when not using hormonal contraception. If hormonal contraception has been used, the following applies:
  • If recently used intramuscular Depo-Provera must have had last injection at least 3 months prior enrollment;
  • If using an IUD or an implant, she is planning to have this removed for purposes unrelated to enrollment in the study prior to entering the efficacy phase;
  • Completion of her last pack of oral contraceptives or completion of effectiveness period for a monthly injection, patch or ring if any has been used prior to entering the efficacy phase;
  • Have intact uterus and at least one ovary;
  • The subject is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions and has duly signed the informed consent form (ICF);
  • Consistent use of effective contraception during the preceding cycle prior to enrolling;
  • No known infertility;
  • Intends to remain in a monogamous relationship with male study partner (as specified above). (Note: this study will not provide her contraception for intercourse with any other male partners);
  • Be at risk for pregnancy with participating male partner (heterosexual vaginal intercourse at least once per cycle and not sterilized);
  • Have a negative pregnancy test at enrollment;
  • Willingness to accept a low but unknown risk of pregnancy and able to understand the need for follow-up in case of pregnancy;
  • No medical contraindication to pregnancy;

Who cannot join

  • Men who meet any of the following criteria are not eligible for enrollment in the trial:
  • Men participating in another clinical trial involving an investigational drug within the last 30 days (or within five half-lives of the investigational drug, whichever is longer) prior to the first screening visit.
  • Men not living in the catchment's area of the study site or within a reasonable distance from the site.
  • Clinically significant abnormal findings at screening per the Investigator's medical judgment.
  • Elevated PSA levels ≥ 4 ng/mL.
  • Abnormal serum chemistry values that may indicate clinically significant liver or kidney dysfunction.
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  • Use of androgens or other anabolic steroids that may suppress gonadotropins within 6 months prior to the first screening visit.
  • Diastolic blood pressure (DBP) ≥ 85 and Systolic blood pressure (SBP) ≥ 135 mm Hg; (BP will be taken three times at approximately 5 minute intervals and the mean of the 2 measurements will be used to determine eligibility).
  • History of hypertension, including hypertension controlled with treatment.
  • Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis.
  • Known hypersensitivity to progestins or testosterone or any excipient of the investigational product.
  • History of prostate, testicular or breast carcinoma.
  • Significant prostatic symptoms (IPSS > 15).
  • Known history of reproductive dysfunction including vasectomy or infertility.
  • Known history of significant cardiac, renal, hepatic or prostatic disease.
  • History of thromboembolic disease.
  • A serious systemic disease such as diabetes mellitus (including diabetes controlled with treatment), HIV/AIDS;
  • Current active or ongoing Hepatitis infection.
  • History of untreated sleep apnea.
  • Known or suspected current alcohol dependence syndrome, chronic marijuana use, or any illicit drug use that may affect metabolism/transformation of steroid hormones and study treatment compliance.
  • Any skin condition that might interfere with absorption of gel.
  • Couples desiring fertility within the study participation period (approximately 104 weeks from screening to end of recovery).
  • PHQ9 score ≥10, a score ≥1 on Question #9 on the PHQ9, or history of severe depression or other serious mental health disorder, including ongoing use of an anti-depressant.
  • Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine. Exclusion is due to the potential of testing positive for androgens that may occur from their study participation coupled with the unknown efficacy (i.e. duration of positive testing) of a single application.
  • Use of sex steroids or medications which might interfere with steroid metabolism (i.e., ketoconazole, finasteride, oral corticosteroids, dutasteride, and statins).
  • Use of anticoagulants.
  • Use of medications that will interfere or interact with Nestorone or Testosterone.
  • Use of oily cosmetic skin gels/products that would prevent absorption of steroids.
  • Previous participation in this clinical trial.
  • Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.
  • 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.
  • Female participant - Exclusion Criteria
  • Desire to become pregnant during the study.
  • Breastfeeding.
  • Known or suspected current alcoholism or drug abuse.
  • Participation in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit.
  • Currently pregnant.
  • Known hypersensitivity to progestins or testosterone.
  • Previous participation in this clinical trial.
  • Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.
  • 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.

Trial locations and contacts

17 sites in 7 countries.

17 sites in 7 countries

United States9 sites

  • Comprehensive Women's Health Center

    Denver, Colorado, 80230

  • University of Kansas

    Kansas City, Kansas, 66160

  • Eastern Virginia Medical School-EVMS Obstetrics & Gynecology

    Norfolk, Virginia, 23507

  • University of Pennsylvania Medical Center

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • UC Davis Health

    Sacramento, California, 95817

  • University of Utah

    Salt Lake City, Utah, 84132

  • University of Washington Medical Center & Health Sciences

    Seattle, Washington, 98195

  • The Lunquist Institute at Harbor-UCLA Medical Center

    Torrance, California, 90509

Other trials in United States

Chile2 sites

  • Centro de Medicina Reproductiva Shady Grove Chile

    Santiago, Vitacura, 7650672

  • Chilean Institute of Reproductive Medicine

    Santiago, 8320000

Other trials in Chile

United Kingdom2 sites

  • University of Edinburgh

    Edinburgh, EH 16 4SA

  • University of Manchester, UK

    Manchester, M13 9WL

Other trials in United Kingdom

Italy1 site

  • University of Bologna, Italy

    Bologna, 40138

Other trials in Italy

Kenya1 site

  • Kenyatta National Hospital

    Nairobi, 00202

Other trials in Kenya

Sweden1 site

  • Karolinska Institutet

    Stockholm

Other trials in Sweden

Zimbabwe1 site

  • Spilhaus Clinical Research Site

    Harare, 00000

Other trials in Zimbabwe

About this study

Official title: Clinical Evaluation of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception

The long term objective is to develop a gel to be used as a male contraceptive.

Read the detailed description

This is a prospective, phase IIb, open label, single arm, multicenter study. The study protocol consists of a screening phase lasting 4 to 8 weeks, a suppression phase estimated up to 20 weeks, a 52-week maintenance/efficacy phase, and a 24-week (estimated) recovery phase.

The study will involve approximately 420 couples recruited throughout the CCTN that meet eligibility criteria. Approximately fifteen sites propose to enroll up to 420 couples (about 30 to 60 couples per site) with a goal of obtaining 200 couples completing the contraceptive efficacy phase of the study. The study has four phases (screening phase, suppression phase, efficacy phase and recovery phase) with monthly visits to provide the male participants with the NES/T gel, to encourage adherence, to monitor for possible side effects, and to quantify semen parameters. The female partner will be contacted monthly and come in for a visit every three months. Male subjects will be treated and followed as outpatients, along with their participating female partner.

Being tested
Nestorone + Testosterone Combination Gel
Keywords
Healthy Men, Couple, Gel, Male Contraception, Nestorone, Testosterone
Medical subject headings
Multiple Endocrine Neoplasia Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nestorone + Testosterone Combination GelDrug

    Also called NES/T gel

    The combined gel is a transdermal treatment that will be applied daily for 52 weeks to a male subject's arms and shoulders. The formulation will be a hydro alcoholic gel. About 9 to 14% of the steroid (T or NES) in the gel applied is available to the body. The amount of gel to be applied each application will be approximately 5 mL in volume.

Study groups in NCT03452111
Study groupRoleWhat they receive
Nestorone (NES) + testosterone (T) combined gelExperimentalA combination Gel with Nestorone® (NES) and Testosterone (T) applied transdermally (NES/T gel). The amount of gel to be applied daily will be approximately 5 mL in volume (2.5 mL to each shoulder and upper arm per day). This daily gel volume will contain approximately 62 mg or 74 mg of T of which 6.2 mg of T with the original dose (Cohort A) and about 7.4mg of T with the second dose (Cohort B) will be absorbed per day (10% skin absorption)
Receives: Drug: Nestorone + Testosterone Combination Gel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Contraceptive efficacy provided by daily application of NES/T gel for 52 wks during the efficacy phase of the study determined using Kaplan-Meier methods to estimate the 12-mth cumulative pregnancy probability in the efficacy(evaluable cycles)population.

    Measured: 12 months

Secondary outcomes (26)

  1. Suppression of spermatogenesis induced by daily use of the NES/T gel as assessed by semen analyses using number of subjects with sperm concentration <1 million (M)/mL during the suppression phase of the study.

    Measured: 20 weeks

  2. Maintenance of suppression of spermatogensis induced by daily use of the NES/T gel as assessed by semen analyses using number of subjects with sperm concentration <1 million (M)/mL during the 52 week efficacy phase of the study.

    Measured: 52 weeks

  3. Changes from baseline in Follicle Stimulating Hormone (FSH) with daily use of the NES/T gel.

    Measured: 24 months

  4. Changes from baseline in Luteinizing Hormone (LH) with daily use of the NES/T gel.

    Measured: 24 months

  5. Changes from baseline in Sex Hormone Binding Globulin (SHBG) with daily use of the NES/T gel.

    Measured: 24 months

  6. Changes from baseline in Testosterone with daily use of the NES/T gel.

    Measured: 24 months

  7. Changes from baseline in Nestorone with daily use of the NES/T gel.

    Measured: 24 months

  8. Incidence of treatment emergent adverse events with daily use of the NES/T gel.

    Measured: 24 months

  9. Changes from baseline in sodium with daily use of the NES/T gel.

    Measured: 24 months

  10. Changes from baseline in potassium with daily use of the NES/T gel.

    Measured: 24 months

  11. Changes from baseline in chloride with daily use of the NES/T gel.

    Measured: 24 months

  12. Changes from baseline in bicarbonate with daily use of the NES/T gel.

    Measured: 24 months

  13. Changes from baseline in fasting glucose with daily use of the NES/T gel.

    Measured: 24 months

  14. Changes from baseline in blood urea nitrogen with daily use of the NES/T gel.

    Measured: 24 months

  15. Changes from baseline in creatinine with daily use of the NES/T gel.

    Measured: 24 months

  16. Changes from baseline in calcium with daily use of the NES/T gel.

    Measured: 24 months

  17. Changes from baseline in total bilirubin with daily use of the NES/T gel.

    Measured: 24 months

  18. Changes from baseline in alkaline phosphatase with daily use of the NES/T gel.

    Measured: 24 months

  19. Changes from baseline in alanine aminotransferase with daily use of the NES/T gel.

    Measured: 24 months

  20. Changes from baseline in aspartate transaminase with daily use of the NES/T gel.

    Measured: 24 months

  21. Changes from baseline in albumin with daily use of the NES/T gel.

    Measured: 24 months

  22. Changes from baseline in mood with daily use of the NES/T gel using the Patient Health Questionnaire-9.

    Measured: 24 months

  23. Changes from baseline in sexual function with daily use of the NES/T gel using the psychosexual daily questionnaire.

    Measured: 24 months

  24. Changes from baseline in prostate function with daily use of NES/T gel using the International Prostate Symptom Score.

    Measured: 24 months

  25. Acceptability of NES/T gel as a contraceptive among male and female participants using the acceptability questionnaires.

    Measured: 24 months

  26. Length of time to recovery of spermatogenesis after daily use of NES/T gel as assessed by sperm concentration > 15 million (M)/mL during the recovery phase.

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2018
  2. Study start25 Oct 2018
  3. Primary completion6 Sep 2024
  4. Study completion6 Sep 2024

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
420 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03452111
Sponsor's protocol ID
CCN017
Status last verified
Feb 2025
First submitted
23 Feb 2018
Last updated
18 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lue Y, Swerdloff R, Pak Y, Nguyen BT, Yuen F, Liu PY, Blithe DL, Wang C. Male contraception development: monitoring effective spermatogenesis suppression utilizing a user-controlled sperm concentration test compared with standard semen analysis. Fertil Steril. 2023 Feb;119(2):208-217. doi: 10.1016/j.fertnstert.2022.11.002. Epub 2022 Nov 5.

    PubMed 36347310

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nestorone + Testosterone Combination Gel in people with Healthy and Men, run by Premier Research at 17 sites in 7 countries.

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 31 inclusion and 41 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 18 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Chile, United Kingdom, Italy, Kenya and 2 more countries. 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?

Contraceptive efficacy provided by daily application of NES/T gel for 52 wks during the efficacy phase of the study determined using Kaplan-Meier methods to estimate the 12-mth cumulative pregnancy probability in the efficacy(evaluable cycles)population. (time frame: 12 months). 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 NCT03452111, which also lists 1 linked publication.

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 18 Feb 2025.

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