NES Gel-1, To Evaluate Nestorone Gel in Combination With Testosterone Gel

Study Overview
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Brief Summary
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The purpose of this study is to determine the usefulness of two transdermal gels to be used in the future development for a male contraceptive.

Detailed Description
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The success of hormonal male contraception depends on the near complete suppression of spermatogenesis without producing any untoward effects on libido or other androgen-dependent functions or any other adverse events. The treatment with androgen alone has geen shown to be highly effective in Asian men but less effective in non-Asian men in clinical trials. To increase the efficacy of androgen alone treatment on spermatogenesis, combined regimens of a progestin and an androgen have shown promising results. The steady-state delivery of a progestin and an androgen by transdermal gel application would be a user-friendly delivery method as compared to injectable or implant approaches. Nestorone (NES) is a synthetic progestin that does not have any androgenic and estrogenic activity and is not expected to have some of the undesirable side effects of other drugs. We propose to evaluate whether NES gel alone or in combination with T gel applied transdermally will result in more effective suppression of gonadotropins than NES or T gel applied alone in healthy men. Fifty healthy male subjects, age 18-50 will be enrolled at each center (2 sites).

Official Title
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A Randomized, Open Label Clinical Trial to Evaluate if Nestorone Gel Has Gonadotropin Suppressive Activity and if Nestorone in Combination With Testosterone Will Have an Additive Effect on Gonadotropin Suppression When Applied Transdermally in Healthy Men

Conditions
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Contraception

Intervention / Treatment
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* Drug: Nestorone gel
* Drug: Testosterone Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men Aged 18-50 years With normal clinical chemistry, serum levels of testosterone, PSA, gonadotropins within normal limits, and sperm concentration greater than 20 million/mL Subject or his partner willing to use a recognized effective method of contraception Exclusion Criteria: Men not living in area of clinics Clinically significant abnormal findings at screening Elevated PSA greater than 4 Partners who are pregnant Abnormal laboratory values, liver or kidney dysfunction Sperm counts below 20 million/mL. Use of androgens or body building substances within 6 months of enrollment, Blood pressure greater than 140/90, history of hypertension, including hypertension controlled with treatment History of primary testicular disease or disorder of the hypothalamic-pituitary axis Hypersensitivity of progestins History of venous thromboembolism Benign or malignant liver tumors Active liver disease, history of reproductive dysfunction including vasectomy or infertility History of active or chronic cardiac, renal, hepatic or prostatic disease Diabetes mellitus or morbid obesity (body weight greater than 120% of ideal body weight) Known or suspected alcoholism or drug abuse Known dermatitis or severe skin disorder Men desiring fertility within 6 months or participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine will be advised of the relative and temporary hazards that participating in this study may have for their fertility or sporting status.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>100 mg Testosterone gel daily for 3 weeks | Drug: Testosterone Gel<br>* 100 mg Testosterone gel daily for 3 weeks<br>* Other names: Testim;|
| Active Comparator: 2<br>2 mg Nestorone gel daily for 3 weeks | Drug: Nestorone gel<br>* 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment<br>|
| Active Comparator: 3<br>4 mg Nestorone gel daily for 3 weeks | Drug: Nestorone gel<br>* 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment<br>|
| Active Comparator: 4<br>100 mg Testosterone gel + 2 mg Nestorone gel | Drug: Nestorone gel<br>* 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment<br>Drug: Testosterone Gel<br>* 100 mg Testosterone gel daily for 3 weeks<br>* Other names: Testim;|
| Active Comparator: 5<br>100 mg Testosterone gel + 4 mg Nestorone gel | Drug: Nestorone gel<br>* 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment<br>Drug: Testosterone Gel<br>* 100 mg Testosterone gel daily for 3 weeks<br>* Other names: Testim;|
| Active Comparator: 6<br>100 mg Testosterone Gel + 6 mg Nestorone Gel daily for 3 weeks | Drug: Nestorone gel<br>* 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment<br>Drug: Testosterone Gel<br>* 100 mg Testosterone gel daily for 3 weeks<br>* Other names: Testim;|
| Active Comparator: 7<br>100 mg Testosterone Gel + 8 mg Nestorone gel daily for 3 weeks | Drug: Nestorone gel<br>* 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment<br>Drug: Testosterone Gel<br>* 100 mg Testosterone gel daily for 3 weeks<br>* Other names: Testim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - To determine the gonadotropin suppressive activity of Nestorone (NES) Gel at two doses and T gel at one dose alone or in combination over a 3-week period. Serum levels of gonadotropins will be assessed in all subjects. |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel. |  | 3 weeks | 
| Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels |  | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Male contraception, Androgen, Progestin, Spermatogenesis, Gonadotropin suppression, Testosterone, Nestorone