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

Phase 1

Completed

Conditions: Healthy Males

Interventions: Drug: Acyline
Other: placebo hCG (no active ingredient)
Drug: hCG (human chorionic gonadotropin)
Drug: Testosterone gel

Registration Number: NCT00839319

Lead Sponsor: University of Washington

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 59

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acyline plus Placebo	Acyline	Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days
Acyline plus Placebo	placebo hCG (no active ingredient)	Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days
Acyline plus 15 IU hCG	hCG (human chorionic gonadotropin)	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
Acyline plus 125 IU hCG	Acyline	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
Acyline plus Testosterone gel	Acyline	Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days
Acyline plus Testosterone gel	Testosterone gel	Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days
Acyline plus 60 IU hCG	hCG (human chorionic gonadotropin)	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
Acyline plus 125 IU hCG	hCG (human chorionic gonadotropin)	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
Acyline plus 60 IU hCG	Acyline	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
Acyline plus 15 IU hCG	Acyline	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

Primary Outcome Measures

Name	Time	Method
Serum Testosterone (T)	10 days
Serum Luteinizing Hormone (LH)	10 days
Serum Follicle Stimulating Hormone (FSH)	10 days
Intratesticular Testosterone (ITT-T)	10 days

Secondary Outcome Measures