Oral T7 Oral Testosterone in Man

NCT00842751 | Completed Phase 2 Results DMC

• 3 other identifiers: 35724-W1K23HD0453865U54HD042454
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Males; Male Contraceptive

Keywords

5α-reductase; androgen; dihydrotestosterone (DHT); drug delivery; oestradiol

Outcome Measures

Primary Outcomes (3)

• 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

• Serum Dihydrotestosterone Concentration

  Area under the curve of serum dihydrotestosterone

  0,1,2,4,8,and 12-hour post dose

• Serum Estradiol Concentration

  Area under the curve of serum estradiol

  0,1,2,4,8,and 12-hour post dose

Study Arms (3)

Testosterone Undecanoate + placebo finasteride

PLACEBO COMPARATOR

Acyline 300mcg/kg subcutaneous on days 1, 15 and 29 + Testosterone Undecanoate (TU)200mg twice daily, orally for 7 days + placebo finasteride twice daily, orally for 7 days during one of the three intervention periods (First Intervention, Second Intervention or Third Intervention)

Drug: First Intervention (7 days); Other: First Washout (7 days)

Testosterone Undecanoate + Finasteride 0.5mg

EXPERIMENTAL

Acyline 300mcg/kg subcutaneous on days 1, 15 \& 29 + testosterone undecanoate 200mg, twice daily orally for 7 days + finasteride 0.5mg twice daily, orally for 7 days during one of the three intervention periods (First Intervention, Second Intervention or Third Intervention)

Drug: Second Intervention (7 days); Other: Second wash-out period

Testosterone Undecanoate + Finasteride 1mg

EXPERIMENTAL

Acyline 300mcg/kg subcutaneous on days 1, 15 \& 29 + testosterone undecanoate 200mg, twice daily orally for 7 days + finasteride 1mg twice daily, orally for 7 days during one of the three intervention periods ((First Intervention, Second Intervention or Third Intervention)

Drug: Third Intervention (7 days)

Interventions

First Intervention (7 days) DRUG

Acyline 300mcg/kg subcutaneous (days 1, 15 \& 29) + testosterone undecanoate 200 mg, twice daily orally + finasteride placebo

Also known as: propecia

Testosterone Undecanoate + placebo finasteride

First Washout (7 days) OTHER

Washout of 7 days between each of the 3 treatment arms

Also known as: no active drugs

Testosterone Undecanoate + placebo finasteride

Second Intervention (7 days) DRUG

Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 0.5mg twice daily, orally

Also known as: propecia

Testosterone Undecanoate + Finasteride 0.5mg

Third Intervention (7 days) DRUG

Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 1mg twice daily, orally

Also known as: propecia

Testosterone Undecanoate + Finasteride 1mg

Second wash-out period OTHER

Washout of 7 days between each of the 3 treatment arms

Also known as: no active drug

Testosterone Undecanoate + Finasteride 0.5mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (20)

• 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. doi: 10.1210/jcem.81.12.8954042.

  PMID: 8954042 BACKGROUND

• 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. doi: 10.1210/jcem.82.8.4163.

  PMID: 9253305 BACKGROUND

• Bhasin S, Bremner WJ. Clinical review 85: Emerging issues in androgen replacement therapy. J Clin Endocrinol Metab. 1997 Jan;82(1):3-8. doi: 10.1210/jcem.82.1.3640. No abstract available.

  PMID: 8989221 BACKGROUND

• 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. doi: 10.1210/jcem.81.10.8855804.

  PMID: 8855804 BACKGROUND

• 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. doi: 10.1210/jcem.85.8.6731.

  PMID: 10946864 BACKGROUND

• 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. doi: 10.1172/JCI106877.

  PMID: 4259253 BACKGROUND

• 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. doi: 10.1172/JCI107526.

  PMID: 4271572 BACKGROUND

• Bagatell CJ, Bremner WJ. Androgens in men--uses and abuses. N Engl J Med. 1996 Mar 14;334(11):707-14. doi: 10.1056/NEJM199603143341107. No abstract available.

  PMID: 8594431 BACKGROUND

• Fossa 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. doi: 10.1016/s0959-8049(99)00123-9.

  PMID: 10615233 BACKGROUND

• Amory JK, Matsumoto AM. The therapeutic potential of testosterone patches. Expert Opin Investig Drugs. 1998 Dec;7(12):1977-85. doi: 10.1517/13543784.7.12.1977.

  PMID: 15991940 BACKGROUND

• 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. doi: 10.1210/jcem.85.12.7045.

  PMID: 11134099 BACKGROUND

• 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. doi: 10.1530/acta.0.0790366.

  PMID: 1173495 BACKGROUND

• Johnsen SG, Bennett EP, Jensen VG. Therapeutic effectiveness of oral testosterone. Lancet. 1974 Dec 21;2(7895):1473-5. doi: 10.1016/s0140-6736(74)90216-5. No abstract available.

  PMID: 4140393 BACKGROUND

• Daggett PR, Wheeler MJ, Nabarro JD. Oral testosterone, a reappraisal. Horm Res. 1978;9(3):121-9. doi: 10.1159/000178904.

  PMID: 640576 BACKGROUND

• 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. doi: 10.1210/jc.2004-1221. Epub 2005 Feb 15.

  PMID: 15713724 BACKGROUND

• 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. doi: 10.2164/jandrol.05058.

  PMID: 16400081 BACKGROUND

• 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. doi: 10.1210/jc.2003-031110.

  PMID: 14764753 BACKGROUND

• 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. doi: 10.1210/jc.2003-032123.

  PMID: 15579744 BACKGROUND

• 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. doi: 10.1210/jc.2006-2203. Epub 2007 Feb 13.

  PMID: 17299062 BACKGROUND

• 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 5alpha-reductase by finasteride. Int J Androl. 2011 Dec;34(6 Pt 1):541-7. doi: 10.1111/j.1365-2605.2010.01120.x. Epub 2010 Oct 24.

  PMID: 20969601 RESULT

MeSH Terms

Interventions

Finasteride

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Azasteroids; Steroids, Heterocyclic

Results Point of Contact

• Title: John Amory, MD
• Organization: University of Washington, Dept. of Medicine

jamory@u.washington.edu

(206) 616-1727

Study Officials

• John K Amory, MD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2009
• First Posted: February 12, 2009
• Study Start: July 1, 2009
• Primary Completion: November 1, 2009
• Study Completion: December 1, 2009
• Last Updated: January 13, 2014
• Results First Posted: January 13, 2014

Record last verified: 2013-12

Locations

US (1)