Oral T-7 Oral Androgens in Man-7

Condition(s) targeted: Healthy Males

Intervention: Acyline (Drug); Testosterone Undecanoate (Drug); Finasteride 0.5 mg (Drug); Finasteride 1 mg (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
John K Amory, MD, MPH, Principal Investigator, Affiliation: University of Washington

Overall contact:
Robert Bale, Phone: 206-221-0521, Email: rfbalejr@u.washington.edu

The purpose of this study is to test how the body absorbs and processes new forms of oral testosterone. Information gained during the study may help develop better forms of testosterone therapy in the future.

Official title: Oral Androgens in Man-7: Pharmacokinetics of a Novel Oral Testosterone Undecanoate Formulation With Concomitant Inhibition of 5alpha-Reductase by Finasteride

Study design: Treatment, Non-Randomized, Open Label, Crossover Assignment, Pharmacokinetics Study

Primary outcome: To determine what dose of Finasteride, when combined with Oral TU, will yield an average serum testosterone over 24 hours in the eugonadal range while at the same time maintaining serum DHT concentrations within the normal range.

Detailed description: We will be using three drugs: The first, acyline, temporarily turns off the body's production of testosterone for about two weeks. Subjects will receive acyline as shots three times over a six-week drug administration period. During the time when the body's production of testosterone is turned off, we will give testosterone either by itself or with a medication called finasteride by mouth twice daily for one week to see how much is absorbed and present in the bloodstream after administration. Subjects will go through three one-week study drug exposure periods. During two of the three one-week study drug administration periods subjects will also take a second medication, finasteride, by mouth twice daily. On the last day of each one-week drug administration period, subjects will be admitted to the University of Washington General Clinical Research Center overnight for monitoring of your blood testosterone levels. There will be 3 overnight visits for this study. This study will allow us to determine the absorption of testosterone taken by mouth, and the relative impact of two different doses of oral finasteride on testosterone absorption.

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

Criteria:

Inclusion Criteria:

- Males between 18 and 50 years of age

- In good health based on normal screening evaluation (consisting of a medical history,

physical exam normal serum chemistry, hematology, and baseline hormone levels.

- Must agree to not participate in another research drug study

- Must agree to not donate blood

- Must be willing to comply with the study protocol and procedures

Exclusion Criteria:

- Men in poor general health, with abnormal blood results (clinical laboratory tests or

hormone values)

- A known history of alcohol or drug abuse

- Participation in a long-term male contraceptive study within the past month

- History of bleeding disorders or current use of anti-coagulants

- History of sleep apnea

- History of major psychiatric disorder

- Body mass index > 37

- Infertility

- Hematocrit > 55 or < 30

- PSA >4

Robert Bale, Phone: 206-221-0521, Email: rfbalejr@u.washington.edu

University of Washington, Seattle, Washington 98195, United States; Recruiting
Robert Bale, Jr., Phone: 206-221-0521, Email: rfbalejr@u.washington.edu
Kathryn Duncan, Phone: 206-616-0482, Email: kymmkatt@u.washington.edu
Mara Y Roth, MD, Sub-Investigator
Christin N Snyder, MD, Sub-Investigator
Stephanie T Page, MD, PhD, Sub-Investigator
Robert E Dudley, PhD, Sub-Investigator
Peter Christiansen, PhD, Sub-Investigator
William J Bremner, MD. PhD, Sub-Investigator

Dedicated to basic and clinical research focused primarily on the male reproduction system.

Related publications:

Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996 Dec;81(12):4358-65.

Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 1997 Aug;82(8):2386-90.

Bhasin S, Bremner WJ. Clinical review 85: Emerging issues in androgen replacement therapy. J Clin Endocrinol Metab. 1997 Jan;82(1):3-8. Review. No abstract available.

Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3578-83.

Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, Santanna J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000 Aug;85(8):2670-7.

Kelch RP, Jenner MR, Weinstein R, Kaplan SL, Grumbach MM. Estradiol and testosterone secretion by human, simian, and canine testes, in males with hypogonadism and in male pseudohermaphrodites with the feminizing testes syndrome. J Clin Invest. 1972 Apr;51(4):824-30.

Weinstein RL, Kelch RP, Jenner MR, Kaplan SL, Grumbach MM. Secretion of unconjugated androgens and estrogens by the normal and abnormal human testis before and after human chorionic gonadotropin. J Clin Invest. 1974 Jan;53(1):1-6.

Bagatell CJ, Bremner WJ. Androgens in men--uses and abuses. N Engl J Med. 1996 Mar 14;334(11):707-14. Review. No abstract available.

Bhasin S, Bremner WJ. Clinical review 85: Emerging issues in androgen replacement therapy. J Clin Endocrinol Metab. 1997 Jan;82(1):3-8. Review. No abstract available.

Fosså SD, Opjordsmoen S, Haug E. Androgen replacement and quality of life in patients treated for bilateral testicular cancer. Eur J Cancer. 1999 Aug;35(8):1220-5.

Amory JK, Matsumoto AM. The therapeutic potential of testosterone patches. Expert Opin Investig Drugs. 1998 Dec;7(12):1977-85.

Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab. 2000 Dec;85(12):4500-10.

Nieschlag E, Mauss J, Coert A, Ki?ovi? P. Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Acta Endocrinol (Copenh). 1975 Jun;79(2):366-74.

Johnsen SG, Bennett EP, Jensen VG. Therapeutic effectiveness of oral testosterone. Lancet. 1974 Dec 21;2(7895):1473-5. No abstract available.

Daggett PR, Wheeler MJ, Nabarro JD. Oral testosterone, a reappraisal. Horm Res. 1978;9(3):121-9.

Amory JK, Bremner WJ. Oral testosterone in oil plus dutasteride in men: a pharmacokinetic study. J Clin Endocrinol Metab. 2005 May;90(5):2610-7. Epub 2005 Feb 15.

Amory JK, Page ST, Bremner WJ. Oral testosterone in oil: pharmacokinetic effects of 5alpha reduction by finasteride or dutasteride and food intake in men. J Androl. 2006 Jan-Feb;27(1):72-8.

Amory JK, Watts NB, Easley KA, Sutton PR, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab. 2004 Feb;89(2):503-10.

Herbst KL, Coviello AD, Page S, Amory JK, Anawalt BD, Bremner WJ. A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men. J Clin Endocrinol Metab. 2004 Dec;89(12):5959-65.

Amory JK, Wang C, Swerdloff RS, Anawalt BD, Matsumoto AM, Bremner WJ, Walker SE, Haberer LJ, Clark RV. The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J Clin Endocrinol Metab. 2007 May;92(5):1659-65. Epub 2007 Feb 13. Erratum in: J Clin Endocrinol Metab. 2007 Nov;92(11):4379.

Starting date: July 2009
Ending date: July 2010
Last updated: August 20, 2009