Clinical trial NCT00229593: NES Gel-1, To Evaluate Nestorone Gel in Combination With Testosterone Gel
Official title: A Randomized, Open Label Clinical Trial to Evaluate if Nestorone Gel Has Gonadotropin Suppressive Activity and if Nestorone in Combination With Testosterone Will Have an Additive Effect on Gonadotropin Suppression When Applied Transdermally in Healthy Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Contraception
Keywords: Male contraception
Androgen
Progestin
Spermatogenesis
Gonadotropin suppression
Testosterone
Nestorone
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2005-09-29
Enrollment: 140
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine the usefulness of two transdermal gels to be used in the future development for a male contraceptive.

Detailed description: The success of hormonal male contraception depends on the near complete suppression of spermatogenesis without producing any untoward effects on libido or other androgen-dependent functions or any other adverse events. The treatment with androgen alone has geen shown to be highly effective in Asian men but less effective in non-Asian men in clinical trials. To increase the efficacy of androgen alone treatment on spermatogenesis, combined regimens of a progestin and an androgen have shown promising results. The steady-state delivery of a progestin and an androgen by transdermal gel application would be a user-friendly delivery method as compared to injectable or implant approaches. Nestorone (NES) is a synthetic progestin that does not have any androgenic and estrogenic activity and is not expected to have some of the undesirable side effects of other drugs.

We propose to evaluate whether NES gel alone or in combination with T gel applied transdermally will result in more effective suppression of gonadotropins than NES or T gel applied alone in healthy men. Fifty healthy male subjects, age 18-50 will be enrolled at each center (2 sites).

Eligibility criteria: Inclusion Criteria:

* Healthy men
* Aged 18-50 years
* With normal clinical chemistry, serum levels of testosterone, PSA, gonadotropins within normal limits, and sperm concentration greater than 20 million/mL
* Subject or his partner willing to use a recognized effective method of contraception

Exclusion Criteria:

* Men not living in area of clinics
* Clinically significant abnormal findings at screening
* Elevated PSA greater than 4
* Partners who are pregnant
* Abnormal laboratory values, liver or kidney dysfunction
* Sperm counts below 20 million/mL.
* Use of androgens or body building substances within 6 months of enrollment,
* Blood pressure greater than 140/90, history of hypertension, including hypertension controlled with treatment
* History of primary testicular disease or disorder of the hypothalamic-pituitary axis
* Hypersensitivity of progestins
* History of venous thromboembolism
* Benign or malignant liver tumors
* Active liver disease, history of reproductive dysfunction including vasectomy or infertility
* History of active or chronic cardiac, renal, hepatic or prostatic disease
* Diabetes mellitus or morbid obesity (body weight greater than 120% of ideal body weight)
* Known or suspected alcoholism or drug abuse
* Known dermatitis or severe skin disorder

Men desiring fertility within 6 months or 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.

Primary outcomes:
measure: - To determine the gonadotropin suppressive activity of Nestorone (NES) Gel at two doses and T gel at one dose alone or in combination over a 3-week period. Serum levels of gonadotropins will be assessed in all subjects.
timeFrame: 3 weeks
Secondary outcomes:
measure: To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel.
timeFrame: 3 weeks
measure: Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: William J Bremner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Christina Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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