Study of the Safety, and Sperm and Gonadotropin Suppression of a Contraceptive Gel in Normal Men

Study Overview
=================
Brief Summary
-----------------
To determine the number of men who have suppression of sperm production when using a daily regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel applied transdermally.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind Comparator Trial of the Safety and Sperm and Gonadotropin Suppression Resulting From Combined Use of Nestorone® Gel (0, 8 or 12 mg NES) and Testosterone Gel (10 g) Compared With Testosterone Gel in Normal Men

Conditions
-----------------
Contraception

Intervention / Treatment
-----------------
* Drug: Testosterone
* Drug: Nestorone®
* Drug: Nestorone®
* Drug: Nestorone®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Men who meet all the following criteria are eligible for enrollment in the trial: Male volunteers in good health as confirmed by physical examination, medical history, and clinical laboratory tests of blood and urine at the time of screening 18 to 50 years of age BMI ≤ 33 calculated as weight in Kg/ (height in cm) 2 No history of hormonal therapy use in the last six months prior to the first screening visit Subject will agree to use a recognized effective method of contraception with his partner (i.e. at a minimum, use double-barrier contraception) during the course of the study treatment and recovery phase In the opinion of the investigator, subject is able to comply with the protocol, understand and sign an informed consent and HIPAA form Does not meet any of the exclusion criteria. Exclusion Criteria: 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 prior to the first screening visit Men not living in the catchment's area of the clinic or within a reasonable distance from the site Clinically significant abnormal findings at screening Elevated PSA (levels ≥ 4 ng/mL), according to local laboratory normal values Abnormal serum chemistry values, according to local laboratory normal values that indicate liver or kidney dysfunction or that may be considered clinically significant. Other abnormal lab values may also be exclusionary, at the discretion of the investigator Sperm concentration below 15 million/mL in more than one of three screening samples Use of androgens or body building substances within 6 months before first screening visit Diastolic (D) blood pressure (BP) ≥ 85 and Systolic (S) BP ≥ 135 mm Hg; (BP will be taken 3 times at 5 minute intervals and the mean of all measurements be considered) 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 Family or personal history of venous thromboembolism Benign or malignant liver tumors; active liver disease History of breast carcinoma Known history of reproductive dysfunction including vasectomy or infertility Known history of cardiac, renal, hepatic or prostatic disease A serious systemic disease such as diabetes mellitus or morbid obesity (body weight greater than 120% of ideal body weight or BMI limitation as above) History of sleep apnea Known or suspected alcoholism or drug abuse that may affect metabolism/transformation of steroid hormones and study treatment compliance Known dermatitis or severe skin disorder Partner is known to be pregnant Men desiring fertility within the first 24 weeks of study participation. Men 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
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Testosterone Gel 10 g and Nestorone® 0 mg per day<br>Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head. | Drug: Testosterone<br>* Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily.<br>Drug: Nestorone®<br>* Nestorone® Gel will be delivered by a pump configured to deliver 4 mL of gel containing 0 mg of Nestorone® by pressing two times with the 2 mL dispenser head.<br>|
| Experimental: Testosterone Gel 10 g and Nestorone® 8 mg per day<br>Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg NES mL gel) by pressing two times with 2 mL dispenser head. | Drug: Testosterone<br>* Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily.<br>Drug: Nestorone®<br>* Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 8 mg of Nestorone®. For 8 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (2 mg Nestorone® mL gel) by pressing two times with 2 mL dispenser head.<br>|
| Experimental: Testosterone Gel 10 g plus Nestorone® Gel 12 mg per day<br>Two individual packets of Testosterone Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of Testosterone on the skin. Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head. | Drug: Testosterone<br>* Two individual packets of T Gel, each with 5 g of gel applied to each arm delivering a total of 100 mg of T on the skin daily.<br>Drug: Nestorone®<br>* Nestorone® Gel will be delivered by a pump configured to deliver a metered volume of Nestorone® Gel containing 12 mg of Nestorone®. For 12 mg Nestorone® dose; Nestorone® Gel will be delivered in 4 mL volume (3 mg Nestorone®/mL gel) by pressing two times with 2 mL dispenser head.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Men Who Have Suppression of Sperm Production ≤1Million/mL Million/mL When Using a Daily Regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel Applied Transdermally. |  | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Men Who Have Suppression of Sperm Production ≤3 Million/mL ≤ 3 Million/mL or Azoospermia When Using a Daily Regimen of Nestorone® Gel (0, 8 or 12 mg) and Testosterone Gel. |  | 24 Weeks | 
| The Number of Men Who Have Azoospermia |  | 24 Weeks | 
| The Impact on Sperm Motility in Men Who Are Not Azoospermic Azoospermic. |  | 24 Weeks | 
| The Impact on Sperm Morphology in Men Who Are Not Azoospermic |  | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Contraception, Male Contraception, Suppression of Sperm Production