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

Sponsors and Collaborators:	University of Washington Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	University of Washington
ClinicalTrials.gov Identifier:	NCT00229593

Purpose

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.

Condition	Intervention	Phase
Contraception	Drug: Nestorone gel Drug: Testosterone Gel	Phase I

Study Type:	Interventional
Study Design:	Diagnostic, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Birth Control

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

- 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Enrollment:	140
Study Start Date:	September 2005
Study Completion Date:	January 2007
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 100 mg Testosterone gel daily for 3 weeks	Drug: Testosterone Gel 100 mg Testosterone gel daily for 3 weeks
2: Active Comparator 2 mg Nestorone gel daily for 3 weeks	Drug: Nestorone gel 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment
3: Active Comparator 4 mg Nestorone gel daily for 3 weeks	Drug: Nestorone gel 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment
4: Active Comparator 100 mg Testosterone gel + 2 mg Nestorone gel	Drug: Nestorone gel 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment Drug: Testosterone Gel 100 mg Testosterone gel daily for 3 weeks
5: Active Comparator 100 mg Testosterone gel + 4 mg Nestorone gel	Drug: Nestorone gel 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment Drug: Testosterone Gel 100 mg Testosterone gel daily for 3 weeks
6: Active Comparator 100 mg Testosterone Gel + 6 mg Nestorone Gel daily for 3 weeks	Drug: Nestorone gel 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment Drug: Testosterone Gel 100 mg Testosterone gel daily for 3 weeks
7: Active Comparator 100 mg Testosterone Gel + 8 mg Nestorone gel daily for 3 weeks	Drug: Nestorone gel 2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment Drug: Testosterone Gel 100 mg Testosterone gel daily for 3 weeks

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

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00229593

Locations

United States, California
Harbor-UCLA Medical Center
Torrance, California, United States, 90509
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195

Sponsors and Collaborators

University of Washington

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:	William J Bremner, MD, PhD	University of Washington
Principal Investigator:	Christina Wang, MD	University of California, Los Angeles

More Information

Additional Information:

http://depts.washington.edu/popctr/ This link exits the ClinicalTrials.gov site

http://gcrc.labiomed.org/endocrinology This link exits the ClinicalTrials.gov site

http://www.labiomed.org This link exits the ClinicalTrials.gov site

Publications:

Mahabadi V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, Christensen PD, Kumar N, Tsong YY, Blithe D, Wang C. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab. 2009 Jul;94(7):2313-20. Epub 2009 Apr 14.

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.

Diaz S, Schiappacasse V, Pavez M, Zepeda A, Moo-Young AJ, Brandeis A, Lahteenmaki 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, Kruger K, von Eckardstein S, Schellschmidt I, Rubig 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, Ploger 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.

Responsible Party:	University of Washington ( William J Bremner, MD, PhD )
Study ID Numbers:	26852-D, HHSN27500002;, 04-3792-D 02
Study First Received:	September 27, 2005
Last Updated:	August 20, 2009
ClinicalTrials.gov Identifier:	NCT00229593 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by University of Washington:

Male contraception
Androgen
Progestin
Spermatogenesis

Gonadotropin suppression
Testosterone
Nestorone

Study placed in the following topic categories:

Antineoplastic Agents, Hormonal
Contraceptive Agents
ST 1435
Hormone Antagonists
Contraceptive Agents, Female
Hormones, Hormone Substitutes, and Hormone Antagonists
Healthy

Methyltestosterone
Hormones
Testosterone 17 beta-cypionate
Testosterone
Anabolic Agents
Progestins
Androgens

Additional relevant MeSH terms:

Antineoplastic Agents, Hormonal
Contraceptive Agents
Antineoplastic Agents
ST 1435
Physiological Effects of Drugs
Contraceptive Agents, Female
Hormones, Hormone Substitutes, and Hormone Antagonists
Reproductive Control Agents

Methyltestosterone
Hormones
Pharmacologic Actions
Testosterone 17 beta-cypionate
Testosterone
Anabolic Agents
Therapeutic Uses
Androgens

ClinicalTrials.gov processed this record on September 03, 2009