NES Gel-1, To Evaluate Nestorone Gel in Combination With Testosterone Gel

Condition(s) targeted: Contraception

Intervention: Nestorone gel (Drug); Testosterone Gel (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
William J Bremner, MD, PhD, Principal Investigator, Affiliation: University of Washington
Christina Wang, MD, Principal Investigator, Affiliation: University of California, Los Angeles

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.

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

Primary outcome: - 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.

Secondary outcome:

To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel.

Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels

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).

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Male.

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.

Harbor-UCLA Medical Center, Torrance, California 90509, United States

University of Washington Medical Center, Seattle, Washington 98195, United States

http://depts.washington.edu/popctr/

http://www.labiomed.org

Related publications:

Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl. 1999 May-Jun;20(3):407-14.

Anderson RA, Kinniburgh D, Baird DT. Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception. J Clin Endocrinol Metab. 2002 Aug;87(8):3640-9.

Bebb RA, Anawalt BD, Christensen RB, Paulsen CA, Bremner WJ, Matsumoto AM. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach. J Clin Endocrinol Metab. 1996 Feb;81(2):757-62.

Brache V, Massai R, Mishell DR, Moo-Young AJ, Alvarez F, Salvatierra AM, Cochon L, Croxatto H, Robbins A, Faundes A. Ovarian function during use of Nestorone(R) subdermal implants. Contraception. 2000 Mar;61(3):199-204.

Cummings DE, Bremner WJ. Prospects for new hormonal male contraceptives. Endocrinol Metab Clin North Am. 1994 Dec;23(4):893-922. Review.

Díaz S, Schiappacasse V, Pavez M, Zepeda A, Moo-Young AJ, Brandeis A, Lähteenmäki P, Croxatto HB. Clinical trial with Nestorone subdermal contraceptive implants. Contraception. 1995 Jan;51(1):33-8.

Gonzalo IT, Swerdloff RS, Nelson AL, Clevenger B, Garcia R, Berman N, Wang C. Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J Clin Endocrinol Metab. 2002 Aug;87(8):3562-72.

Haukkamaa M, Laurikka-Routti M, Heikinheimo O, Moo-Young A. Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study. Contraception. 1992 Jan;45(1):49-55.

Handelsman DJ, Conway AJ, Howe CJ, Turner L, Mackey MA. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab. 1996 Nov;81(11):4113-21.

Kamischke A, Heuermann T, Krüger K, von Eckardstein S, Schellschmidt I, Rübig A, Nieschlag E. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. J Clin Endocrinol Metab. 2002 Feb;87(2):530-9.

Kamischke A, Venherm S, Plöger D, von Eckardstein S, Nieschlag E. Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab. 2001 Jan;86(1):303-9.

Starting date: September 2005
Last updated: December 3, 2014