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

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.

Study Type: Interventional

Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Study Primary Completion Date: November 2010

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.

Intervention(s) in this Clinical Trial

• Drug: Acyline
  • 300 ug/kg subcutaneous injections on Day 1.
• Other: placebo hCG (no active ingredient)
  • placebo hCG
• Drug: hCG (human chorionic gonadotropin)
  • 15 IU subcutaneous injection every other day for 10 days (5 doses)
• Drug: hCG (human chorionic gonadotropin)
  • 60 IU subcutaneous injection
• Drug: hCG (human chorionic gonadotropin)
  • 125 IU subcutaneous injection
• Drug: Testosterone gel
  • 75 mg testosterone gel applied transdermally for 10 days

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Group 1
  • Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days
• Experimental: Group 2
  • 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
• Experimental: Group 3
  • 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
• Experimental: Group 4
  • 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
• Experimental: Group 5
  • Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days

Primary Measures

• To clarify the dose-response relationship between low does of hCG and intratesticular testosterone
  • Time Frame: 10-days
    Safety Issue?: No

Secondary Measures

• To determine whether physiologic does of exogenous testosterone contributes to intratesticular testosterone concentrations.
  • Time Frame: 10-days
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Washington

Overall Clinical Trial Officials and Contacts

William Bremner, MD, PhD Principal Investigator University of Washington  

Information obtained from ClinicalTrials.gov on September 02, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00839319

Study ID Number: 27158-D

ClinicalTrials.gov Identifier: NCT00839319

Health Authority: United States: Food and Drug Administration

Dedicated to basic and clinical research focused primarily on the male reproductive system