HOP-3 Manipulation of the Intratesticular Hormonal Milieu With Exogenous Testosterone

Study Overview
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Brief Summary
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The purpose of this investigational study is to determine how much male hormone, testosterone, is necessary to maintain sperm production in the testis. This knowledge will be used to help in the development of a safe male hormonal contraception.

Detailed Description
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Three study drugs will be used in this study: Testim (testosterone gel), Human Chorionic Gonadotropin (hCG) and acyline. Testosterone is a naturally occurring hormone in men. When given to normal men, testosterone gel will temporarily lower the amount of testosterone in the testes and lower sperm counts. hCG is a female hormone produced during pregnancy that is similar to and has the same actions as a male hormone, luteinizing hormone (LH). Like LH, hCG stimulates the testis to produce testosterone and sperm, and is used in the treatment of men who are deficient in LH. When hCG is given together with testosterone to normal men, the amount of testosterone in the testes will change, dependent on the amount of hCG received. Some participants will receive placebo hCG injections (no active medication). Acyline suppresses LH (luteinizing hormone) and FSH (follicle stimulating hormone), which are hormones made by the pituitary gland in the brain, thus blocking the signal from the brain that causes the testes to make testosterone. Therefore, acyline blocks testosterone production. Men may experience some side effects from the low levels of testosterone caused by acyline. Acyline is an experimental drug. Testosterone gel and hCG are approved for use in men with low testosterone levels. The U.S. Food and Drug Administration (FDA) allows testosterone gel, hCG and acyline to be given in combination for research to a small number of volunteers. Over 125 men have received acyline. Both Acyline and hCG will be given by injection. Acyline injections are formulated by subjects weight and may be given in multiple injections. Participation will last approximately 2 months. The study involves a minimum of 9 visits in Seattle, WA. Clinic visits at Screening, Day 1 and Day 10 will take about 1-1.5 hours each. On Day 1 & 10 a fine needle aspiration of one testis will be performed. The Day 7, Day 17, and Day 40 visits will take approximately 30 minutes. The other visits will take about 15 minutes each time. Over the course of the study, which includes 5 separate blood draws, approximately 12 ounces (one and a half cups) of blood will be drawn. Some of the study drugs will be given by injection. One drug is a topical gel. This is NOT a trial of a male contraceptive, and the study medications will not prevent pregnancy. Subjects must use an acceptable form of birth control.

Official Title
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Manipulation of the Intratesticular Hormonal Milieu With Exogenous Testosterone (Short Title (HOP-3)

Conditions
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Healthy Males

Intervention / Treatment
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* Drug: Acyline
* Other: placebo hCG (no active ingredient)
* Drug: hCG (human chorionic gonadotropin)
* Drug: hCG (human chorionic gonadotropin)
* Drug: hCG (human chorionic gonadotropin)
* Drug: Testosterone gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males age 18-50 Normal serum testosterone, LH and FSH PSA < 4.0 Agrees not to donate blood or participate in another research study during the study Informed consent In general good health based on normal screening evaluation (consisting of a medical history, physical exam, normal sperm count, normal serum chemistry and hematology) Must be willing to use a reliable form of contraception during the study Exclusion Criteria: Oligospermia (sperm count < 15 million/mL after 48 hours of abstinence) and/or abnormal motility or morphology. Participation in a long-term male contraceptive study within the past three months History of testosterone or anabolic steroid abuse in the past Poor general health with significantly abnormal blood results History of or current testicular disease History of a bleeding disorder or need for anticoagulation History of sleep apnea and/or major psychiatric problems BMI > 32 Subjects with a skin condition that might interfere or be exacerbated by testosterone gel use Subject's with alcohol or drug use

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acyline plus Placebo<br>Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days | Drug: Acyline<br>* 300 ug/kg subcutaneous injections on Day 1.<br>* Other names: Acyline GhRH antagonist;Other: placebo hCG (no active ingredient)<br>* placebo hCG<br>* Other names: placebo drug;|
| Experimental: Acyline plus 15 IU hCG<br>Acyline 300 ug/kg (SQ) inj(s) on Day 1 plus subcutaneous 15 IU hCG injection (inj) every other day (5 doses) for 10 days | Drug: Acyline<br>* 300 ug/kg subcutaneous injections on Day 1.<br>* Other names: Acyline GhRH antagonist;Drug: hCG (human chorionic gonadotropin)<br>* 15 IU subcutaneous injection every other day for 10 days (5 doses)<br>* Other names: Pregnyl;|
| Experimental: Acyline plus 60 IU hCG<br>Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous 60 IU hCG injection (inj) every other day (5 doses) for 10 days | Drug: Acyline<br>* 300 ug/kg subcutaneous injections on Day 1.<br>* Other names: Acyline GhRH antagonist;Drug: hCG (human chorionic gonadotropin)<br>* 60 IU subcutaneous injection<br>* Other names: Pregnyl;|
| Experimental: Acyline plus 125 IU hCG<br>Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous 125 IU hCG injection (inj) every other day (5 doses) for 10 days | Drug: Acyline<br>* 300 ug/kg subcutaneous injections on Day 1.<br>* Other names: Acyline GhRH antagonist;Drug: hCG (human chorionic gonadotropin)<br>* 125 IU subcutaneous injection<br>* Other names: Pregnyl;|
| Experimental: Acyline plus Testosterone gel<br>Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days | Drug: Acyline<br>* 300 ug/kg subcutaneous injections on Day 1.<br>* Other names: Acyline GhRH antagonist;Drug: Testosterone gel<br>* 75 mg testosterone gel applied transdermally for 10 days<br>* Other names: Testim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Testosterone (T) |  | 10 days | 
| Serum Luteinizing Hormone (LH) |  | 10 days | 
| Serum Follicle Stimulating Hormone (FSH) |  | 10 days | 
| Intratesticular Testosterone (ITT-T) |  | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hCG, testosterone, Acyline, Intratesticular hormone