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Key inclusion & exclusion criteria
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Inclusion Male participant - Inclusion Criteria
Men who meet all the following criteria will be eligible for enrollment in the trial:
1. Good health as confirmed by medical history, physical examination, and clinical
laboratory tests of blood and urine at the time of screening;
2. 18 to 50 years of age, at the enrollment visit;
3. BMI < 33 kg/m2;
4. No history of androgen use in the six months prior to the first screening visit;
5. 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;
6. 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;
7. 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);
8. 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;
9. No known infertility;
10. 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;
11. 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:
1. Good general health with no chronic medical conditions that result in periodic
exacerbations which require significant medical care or are known to affect fertility;
2. Aged between 18 and 34 years, inclusive, at the enrollment visit;
3. 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:
1. If recently used intramuscular Depo-Provera must have had last injection at least
3 months prior enrollment;
2. 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;
3. 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;
4. Have intact uterus and at least one ovary;
5. 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);
6. Consistent use of effective contraception during the preceding cycle prior to
enrolling;
7. No known infertility;
8. 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);
9. Be at risk for pregnancy with participating male partner (heterosexual vaginal
intercourse at least once per cycle and not sterilized);
10. Have a negative pregnancy test at enrollment;
11. Willingness to accept a low but unknown risk of pregnancy and able to understand the
need for follow-up in case of pregnancy;
12. No medical contraindication to pregnancy;
Exclusion Male participant - Exclusion Criteria
Men who meet any of the following criteria are not eligible for enrollment in the trial:
1. 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.
2. Men not living in the catchment's area of the study site or within a reasonable
distance from the site.
3. Clinically significant abnormal findings at screening per the Investigator's medical
judgment.
4. Elevated PSA levels = 4 ng/mL.
5. Abnormal serum chemistry values that may indicate clinically significant liver or
kidney dysfunction.
6. Use of androgens or other anabolic steroids that may suppress gonadotropins within 6
months prior to the first screening visit.
7. 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).
8. History of hypertension, including hypertension controlled with treatment.
9. Known history of primary testicular disease or disorders of the hypothalamic-pituitary
axis.
10. Known hypersensitivity to progestins or testosterone or any excipient of the
investigational product.
11. History of prostate, testicular or breast carcinoma.
12. Significant prostatic symptoms (IPSS > 15).
13. Known history of reproductive dysfunction including vasectomy or infertility.
14. Known history of significant cardiac, renal, hepatic or prostatic disease.
15. History of thromboembolic disease.
16. A serious systemic disease such as diabetes mellitus (including diabetes controlled
with treatment), HIV/AIDS;
17. Current active or ongoing Hepatitis infection.
18. History of untreated sleep apnea.
19. 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.
20. Any skin condition that might interfere with absorption of gel.
21. Couples desiring fertility within the study participation period (approximately 104
weeks from screening to end of recovery).
22. 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.
Age minimum:
18 Years
Age maximum:
50 Years
Gender:
All
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Secondary Outcome(s)
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Changes from baseline in aspartate transaminase with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in chloride with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in Luteinizing Hormone (LH) with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in Testosterone with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in total bilirubin with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in calcium with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in fasting glucose with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in mood with daily use of the NES/T gel using the Patient Health Questionnaire-9.
[Time Frame: 24 months]
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Changes from baseline in Nestorone with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in sodium with daily use of the NES/T gel.
[Time Frame: 24 months]
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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.
[Time Frame: 24 weeks]
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Acceptability of NES/T gel as a contraceptive among male and female participants using the acceptability questionnaires.
[Time Frame: 24 months]
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Changes from baseline in Follicle Stimulating Hormone (FSH) with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in prostate function with daily use of NES/T gel using the International Prostate Symptom Score.
[Time Frame: 24 months]
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Changes from baseline in Sex Hormone Binding Globulin (SHBG) with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in alanine aminotransferase with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in creatinine with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in sexual function with daily use of the NES/T gel using the psychosexual daily questionnaire.
[Time Frame: 24 months]
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Changes from baseline in albumin with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in bicarbonate with daily use of the NES/T gel.
[Time Frame: 24 months]
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Incidence of treatment emergent adverse events with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in alkaline phosphatase with daily use of the NES/T gel.
[Time Frame: 24 months]
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Changes from baseline in blood urea nitrogen with daily use of the NES/T gel.
[Time Frame: 24 months]
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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.
[Time Frame: 52 weeks]
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Changes from baseline in potassium with daily use of the NES/T gel.
[Time Frame: 24 months]
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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.
[Time Frame: 20 weeks]
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