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
Overview
- Phase
- Phase 1
- Intervention
- Testosterone Gel
- Conditions
- Contraception
- Sponsor
- University of Washington
- Enrollment
- 140
- Locations
- 2
- Primary Endpoint
- - 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.
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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).
Investigators
William Bremner
Study Principal Investigator
University of Washington
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
Arms & Interventions
1
100 mg Testosterone gel daily for 3 weeks
Intervention: Testosterone Gel
2
2 mg Nestorone gel daily for 3 weeks
Intervention: Nestorone gel
3
4 mg Nestorone gel daily for 3 weeks
Intervention: Nestorone gel
4
100 mg Testosterone gel + 2 mg Nestorone gel
Intervention: Nestorone gel
4
100 mg Testosterone gel + 2 mg Nestorone gel
Intervention: Testosterone Gel
5
100 mg Testosterone gel + 4 mg Nestorone gel
Intervention: Nestorone gel
5
100 mg Testosterone gel + 4 mg Nestorone gel
Intervention: Testosterone Gel
6
100 mg Testosterone Gel + 6 mg Nestorone Gel daily for 3 weeks
Intervention: Nestorone gel
6
100 mg Testosterone Gel + 6 mg Nestorone Gel daily for 3 weeks
Intervention: Testosterone Gel
7
100 mg Testosterone Gel + 8 mg Nestorone gel daily for 3 weeks
Intervention: Nestorone gel
7
100 mg Testosterone Gel + 8 mg Nestorone gel daily for 3 weeks
Intervention: Testosterone Gel
Outcomes
Primary Outcomes
- 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.
Time Frame: 3 weeks
Secondary Outcomes
- To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel.(3 weeks)
- Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels(3 weeks)