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

Contraception Clinical Trial

— NES-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00229593
• Other study ID #: 26852-D
• Secondary ID: HHSN27500002;04-
• Status: Completed
• Phase: Phase 1
• First received: September 27, 2005
• Last updated: December 3, 2014
• Start date: September 2005
• Est. completion date: January 2007

Study information

• Verified date: December 2014
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: January 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Contraception

Intervention

Drug:
• Nestorone gel
2 to 8 mg Nestorone gel daily for 3 weeks depending on treatment group assignment
• Testosterone Gel
100 mg Testosterone gel daily for 3 weeks

Locations

Country	Name	City	State
United States	University of Washington Medical Center	Seattle	Washington
United States	Harbor-UCLA Medical Center	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- 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.		3 weeks	No
Secondary	To determine the effects on serum levels of total and free testosterone and SHBG and measure serum levels of NES gel.		3 weeks	No
Secondary	Safety measured laboratory evaluations, vitals, pre- and post treatment physical exam results and PSA levels		3 weeks	Yes

External Links

•   http://depts.washington.edu/popctr/
•   http://www.labiomed.org