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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23HD045386 | U.S. NIH Grant/Contract | View source | |
| 5U54HD042454 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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) |
|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| First Intervention (7 days) | Drug | Acyline 300mcg/kg subcutaneous (days 1, 15 & 29) + testosterone undecanoate 200 mg, twice daily orally + finasteride placebo |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John K Amory, MD, MPH | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Washington | Seattle | Washington | 98195 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8954042 | Background | 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. | |
| 9253305 | 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. |
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12 subjects were screened; 11 enrolled (1 did not meet inclusion criteria-abnormal liver function test at baseline and excessive alcohol use). Each subject was administered each of the three treatments over a 6-week period with 1 week of no treatment (wash-out) between each of the treatment period.
Men age 18-52 in good health were recruited through local newspapers and college campus flyers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Acyline + Testosterone Undecanoate + Placebo Finasteride | Acyline 300 mcg/kg +Testosterone Undecanoate 200 mg, BID orally + placebo finasteride |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Each subject was administered each of the three treatments over a 6-week period with 1 week of no treatment (wash-out) between each of the treatment period.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participant received all treatments and is, therefore, included in the analysis population for all groups. | Posted | Dec 2010 | Geometric Mean | Inter-Quartile Range | ng*hr/dL | 0,1,2,4,8,and 12-hour post dose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | First Intervention | Acyline 300mcg/kg subcutaneous on days 1, 15 & 29 + Testosterone Undecanoate 200 mg, twice daily, orally + Finasteride placebo, twice daily, orally |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Depression | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Amory, MD | University of Washington, Dept. of Medicine | (206) 616-1727 | jamory@u.washington.edu |
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| ID | Term |
|---|---|
| D018120 | Finasteride |
| ID | Term |
|---|---|
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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|
| First Washout (7 days) | Other | Washout of 7 days between each of the 3 treatment arms |
|
|
| Second Intervention (7 days) | Drug | Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 0.5mg twice daily, orally |
|
|
| Third Intervention (7 days) | Drug | Acyline 300mcg/kg subcutaneous + testosterone undecanoate 200 mg, twice daily orally + finasteride 1mg twice daily, orally |
|
|
| Second wash-out period | Other | Washout of 7 days between each of the 3 treatment arms |
|
|
| 8989221 | 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. |
| 8855804 | 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. |
| 10946864 | 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. |
| 4259253 | 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. |
| 4271572 | 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. |
| 8594431 | 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. |
| 10615233 | 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. |
| 15991940 | 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. |
| 11134099 | 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. |
| 1173495 | 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. |
| 4140393 | 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. |
| 640576 | Background | Daggett PR, Wheeler MJ, Nabarro JD. Oral testosterone, a reappraisal. Horm Res. 1978;9(3):121-9. doi: 10.1159/000178904. |
| 15713724 | 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. |
| 16400081 | 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. |
| 14764753 | 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. |
| 15579744 | 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. |
| 17299062 | 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. |
| 20969601 | Result | 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. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Height | Mean | Standard Deviation | cm |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m2 |
|
| Serum testosterone concentration | Mean | Standard Deviation | ng/dL |
|
| Serum dihydrotestosterone concentration | Mean | Standard Deviation | ng/dL |
|
| Serum oestradiol concentration | Median | Standard Deviation | pg/mL |
|
Acyline 300 mcg/kg SC + Testosterone Undecanoate 200 mg, BID orally + Finasteride 0.5 mg, BID orally |
| OG002 | Acyline +Testosterone Undecanoate + 1mg Finasteride | Acyline 300 mcg/kg SC + Testosterone Undecanoate 200 mg, BID orally + Finasteride 1 mg, BID orally |
|
|
| Primary | Serum Dihydrotestosterone Concentration | Area under the curve of serum dihydrotestosterone | All participants received all treatment, and is therefore, included in the analysis population for all three treatment groups. | Posted | Dec 2010 | Geometric Mean | Inter-Quartile Range | ng*hr/dL | 0,1,2,4,8,and 12-hour post dose |
|
|
|
| Primary | Serum Estradiol Concentration | Area under the curve of serum estradiol | All participants received all treatment, and is therefore, included in the analysis population for all three treatment groups. | Posted | Dec 2010 | Geometric Mean | Inter-Quartile Range | ng*hr/dL | 0,1,2,4,8,and 12-hour post dose |
|
|
|
| 0 |
| 11 |
| 4 |
| 11 |
| EG001 | Second Intervention | Acyline 300mcg/kg subcutaneous on days 1, 15 & 29 + Testosterone Undecanoate 200 mg, BID orally + Finasteride 0.5mg, twice a day, orally | 0 | 11 | 2 | 11 |
| EG002 | Third Intervention | Acyline 300mcg/kg subcutaneous on days 1, 15 & 29 + Testosterone Undecanoate 200 mg, twice daily orally + Finasteride 1mg, twice a day, orally | 0 | 11 | 3 | 11 |
| Headache | Nervous system disorders | Systematic Assessment |
|
| Hot flashes | Reproductive system and breast disorders | Systematic Assessment |
|
| Testicular Pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Upset Stomach & Reflux | Gastrointestinal disorders | Systematic Assessment |
|
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| D011083 |
| Polycyclic Compounds |
| D001378 | Azasteroids |
| D013260 | Steroids, Heterocyclic |