Evaluate the Pharmacokinetics and Gonadotropin Suppression of Nestorone®-Testosterone (NES/T) Combination Gel in Men

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blinded, two-center trial to evaluate the gonadotropin suppressive activity of transdermal treatment with a combined NES/T gel, or T gel alone, for 28 days.

Detailed Description
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A total of 45 subjects will be enrolled and randomized in a 2:1 ratio to one of two treatment groups. A description of each group is as follows: Group 1 (30 subjects): 5.0 mL of the 1.62% combined gel (containing 8.3 mg NES + 62.5 mg T) applied each day on the arms and shoulders Group 2 (15 subjects): 4.4 mL of the 1.62% AndrogelTM (containing 62.7 mg T) applied each day to the arms and shoulders The total duration of treatment will be 28 days followed by a 72 hour sampling period to assess half-life and a recovery period of at least 28 days, at which point the subjects will return to the clinic for an end of study visit.

Official Title
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A Randomized, Two Center, Double-Blind Trial to Evaluate the Pharmacokinetics and Gonadotropin Suppression of Nestorone®-Testosterone (NES/T) Combination Gel in Healthy Men

Conditions
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Healthy

Intervention / Treatment
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* Drug: Nestorone® /testosterone gel
* Drug: Testosterone only gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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, condom for the male partner and an effective contraception for the female partner) 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. Sperm concentration ≥ 15 million sperm per milliliter ejaculate. Exclusion Criteria: 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 physical 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; Use of androgens or body building substances within 6 months before first screening visit; Diastolic blood pressure (DBP) > 80 and/or Systolic (SBP) > 130 mm Hg; EKG abnormal and clinically significant and QTC level longer than 450msec; 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 androgen; Family or personal history of venous thromboembolism; Benign or malignant liver tumors; active liver disease; Known history of reproductive dysfunction including vasectomy or infertility; Known history of cardiovascular, 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); 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; Moderate or severe depression as determined by PHQ-9 score >15; Partner is known to be pregnant; Known or suspected breast or prostate cancer; Allergic to any ingredient in testosterone/nestorone gel, including alcohol; Known history of untreated sleep apnea; International Prostate Symptom Score (IPSS) greater than or equal to 15.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>5.0 mL of the 1.62% Nestorone® /testosterone gel (containing 8.3 mg NES + 62.5 mg T) applied each day on the arms and shoulders | Drug: Nestorone® /testosterone gel<br>* Nestorone® /testosterone combined gel<br>|
| Experimental: Group 2<br>4.4 mL of the 1.62% Testosterone only gel (AndrogelTM) (containing 62.7 mg T) applied each day to the arms and shoulders | Drug: Testosterone only gel<br>* Testosterone only gel<br>* Other names: Androgel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gonadotropin Suppression | To quantify the gonadotropin suppressive activity of 4 weeks daily therapy of a combination transdermal gel containing 8.3 mg Nestorone® (NES) gel and 62.5 mg (1.62%) testosterone (T) gel, and of T gel (1.62%) alone. Specifically, the proportion (and 95% CI) of men who suppress both gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) to ≤ 1 IU/L in each group, will be quantified. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gonadotropin and follicle-stimulating hormone suppression | • To quantify the proportion (and 95% CI) of men who suppress both gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) to the detection limit of the assay in each group. | 4 weeks | 
| Change in LH and FSH concentrations | • To quantify the median percent change from baseline to week 4 and interquartile range for serum gonadotropins (LH and FSH) concentrations for each treatment group. | 4 weeks | 
| Acceptability and Satisfaction as measured by the Contraceptive Gel Acceptability and Satisfaction Questionnaire by comparing T and NES serum concentrations. | Serum hormone samples for Nes and T will be drawn before gel application on days 1, 7, 11, 14, 21, 25 and 28. | Multiple times on Day 1 | 
| Acceptability and Satisfaction as measured by the Contraceptive Gel Acceptability and Satisfaction Questionnaire by comparing T and NES serum concentrations. | • To compare T and NES concentrations at week 3 and at week 4 using the combined NES/T gel to prior serum concentrations obtained with individual T and NES gel applications at week 3 (CCN005), and week 4 (CCN007), respectively (historical comparison). | 4 weeks | 
| A composite safety of the combined gel determined by outcomes of CBC, chemistry, AEs, vitals, physical changes, and Psychosexual & Patient Health Questionnaires which will all be measured at multiple time points throughout the study. | General composite safety as measured various times during the study by CBC, chemistry, AEs, vital signs, general pre- and post-treatment physical exams and PSA levels. In addition to the above composite measures, another safety outcomes to be included in the overall composite safety review will include changes in mood based on Patient Health Questionnaire and changes in sexual function based on Psychosexual Safety outcomes, both measured by a questionnaire. | 4 weeks | 
| Assessing sexual function by compare gonadotropin suppressive activity of T and NES against T alone through the Psychosexual Daily questionnaire. | LH, FSH, T levels in serum will be assayed at screening plus treatment days 1, 7, 11, 14, 21, 25, 28, 30, 31 and at study exit. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spermatogenesis, androgen, male contraception