Oral T7 Oral Testosterone in Man

Healthy Males Clinical Trial

— Oral T7  

Official title:

Pharmacokinetics of a Novel Oral Testosterone Undecanoate Formulation With Concomitant Inhibition of 5alpha-Reductase by Finasteride

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00842751
• Other study ID #: 35724-W
• Secondary ID: 1K23HD0453865U54
• Status: Completed
• Phase: Phase 2
• First received: February 10, 2009
• Last updated: December 10, 2013
• Start date: July 2009
• Est. completion date: December 2009

Study information

• Verified date: December 2013
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Males
• Male Contraceptive

Intervention

Drug:
• First Intervention (7 days)
Acyline 300mcg/kg subcutaneous (days 1, 15 & 29) + testosterone undecanoate 200 mg, twice daily orally + finasteride placebo

Other:
• First Washout (7 days)
Washout of 7 days between each of the 3 treatment arms

Drug:
• Second Intervention (7 days)
Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 0.5mg twice daily, orally
• Third Intervention (7 days)
Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 1mg twice daily, orally

Other:
• Second wash-out period
Washout of 7 days between each of the 3 treatment arms

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (3)

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

Country where clinical trial is conducted

United States, 

References & Publications (20)

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

Bagatell CJ, Bremner WJ. Androgens in men--uses and abuses. N Engl J Med. 1996 Mar 14;334(11):707-14. Review. — View Citation

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. — View Citation

Bhasin S, Bremner WJ. Clinical review 85: Emerging issues in androgen replacement therapy. J Clin Endocrinol Metab. 1997 Jan;82(1):3-8. Review. — View Citation

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

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. — View Citation

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. — View Citation

Johnsen SG, Bennett EP, Jensen VG. Therapeutic effectiveness of oral testosterone. Lancet. 1974 Dec 21;2(7895):1473-5. — View Citation

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. — View Citation

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. — View Citation

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

Roth MY, Dudley RE, Hull L, Leung A, Christenson P, Wang C, Swerdloff R, Amory JK. Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5a-reductase by finasteride. Int J Androl. 2011 Dec;34(6 Pt 1):541-7. doi: 10. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Testosterone Concentration	Area under the curve of serum testosterone Pharmacokinetic measures time-weighted mean concentration calculated as area under the concentration curve (AUC) divided by time from initiation of dosing for the morning dose and corrected for differences in baseline hormone concentration.	0,1,2,4,8,and 12-hour post dose	No
Primary	Serum Dihydrotestosterone Concentration	Area under the curve of serum dihydrotestosterone	0,1,2,4,8,and 12-hour post dose	No
Primary	Serum Estradiol Concentration	Area under the curve of serum estradiol	0,1,2,4,8,and 12-hour post dose	No

External Links

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