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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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The purpose of this study is to test how the body absorbs a new form of oral testosterone (T). On Day 1 and Day 9 there are overnight stays in the General Clinical Research Center at the University of Washington to monitor blood testosterone levels over a 24-hour period.
We will administer two experimental drugs, acyline and oral testosterone. Acyline shots will be given on Day 0 to turn off the body's testosterone production for about 10-14 days.
The next day, Day 1, subjects begin taking 300 mg modified slow-release testosterone pill by mouth, three times a day, around 9 AM, 1 PM, and 7 PM for a total of 27 pills.
There are overnight stays on Day 1 and Day 9 to allow monitoring of blood testosterone levels over a 24 hour period, from @9 AM to 9 AM the next morning. At those visits, blood is drawn at baseline (before taking the pill) and at 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours after the morning dose.
Acyline is an experimental drug. The FDA allows its use only in research with a small number of volunteers. We have used acyline in over 125 men without serious side effects. The use of testosterone in this study is experimental and there may be unknown or unanticipated risks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acyline and oral testosterone | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Testosterone | Drug | Oral Testosterone: 300 mg, pills, three times daily Day 1 - 10 (total of 27 pills) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Testosterone Concentration | initial pharmacokinetics [PK] (day 1) of oral testosterone dosed 3 times daily and the PK after 9 days of treatment | baseline & day 9 |
| Mean Testosterone Concentration | initial 24-hour pharmacokinetics (PK) of oral testosterone dosed 3 times daily and post 24-hour PK after 9 days of treatment | baseline & day 9 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Dihydrotestosterone (DHT) Concentration | baseline & day 9 | |
| Mean Dihydrotestosterone (DHT) Concentration | baseline & day 9 | |
| Maximum Sex Hormone-Binding Globulin (SHGB)Concentration |
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INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| John K Amory, MD | 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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14 subjects were screened and 2 did not meet inclusion criteria for untreated high blood pressure and peripheral arterial disease.
Subjects were recruited through news media (website)and college campus bulletin boards in Seattle, WA. between July-September 2010. All visits were at the University of Washington, Seattle, WA.
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| ID | Title | Description |
|---|---|---|
| FG000 | Acyline and 0ral Testosterone | Acyline 300 mcg/kg subcutaneous + 300mg modified slow-release oral testosterone tid |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Acyline and Oral Testosterone | 300 mcg/kg acyline, and modified slow-release oral testosterone 300 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Median |
| 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 | initial pharmacokinetics [PK] (day 1) of oral testosterone dosed 3 times daily and the PK after 9 days of treatment | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
4 months, July - October 2010
The first subject was screened 7/13/2010; the last subject exited 10/25/2010. Subjects in the study are asked about adverse events and concomitant medications at every visit.
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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 | Acyline and Oral Testosterone | 300 mcg/kg acyline, and modified slow-release oral testosterone 300 mg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hypogonadal symptoms | Endocrine disorders | Systematic Assessment | low libido, irritability |
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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 |
|---|---|
| D013739 | Testosterone |
| C109238 | acyline |
| ID | Term |
|---|---|
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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| Acyline | Drug | 300 ug/kg injection on Day 0 |
|
| baseline & day 9 |
| Mean SHGB Concentration | baseline & day 9 |
| Maximum Estradiol Concentration | baseline & day 9 |
| Mean Estradiol Concentration | baseline & day 9 |
| Free T Maximum Concentration | Free T normal range 4.7-18 ng/dL | baseline & day 9 |
| Free Testosterone Mean Concentration | Free T normal range 4.7-18 ng/dL | baseline & day 9 |
| 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. |
| 12107227 | Background | Herbst KL, Anawalt BD, Amory JK, Bremner WJ. Acyline: the first study in humans of a potent, new gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab. 2002 Jul;87(7):3215-20. doi: 10.1210/jcem.87.7.8675. |
| 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. |
| 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. |
| 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. |
| 20378927 | Background | Snyder CN, Clark RV, Caricofe RB, Bush MA, Roth MY, Page ST, Bremner WJ, Amory JK. Pharmacokinetics of 2 novel formulations of modified-release oral testosterone alone and with finasteride in normal men with experimental hypogonadism. J Androl. 2010 Nov-Dec;31(6):527-35. doi: 10.2164/jandrol.109.009746. Epub 2010 Apr 8. |
| 18948313 | Background | de Ronde W. Hyperandrogenism after transfer of topical testosterone gel: case report and review of published and unpublished studies. Hum Reprod. 2009 Feb;24(2):425-8. doi: 10.1093/humrep/den372. Epub 2008 Oct 23. |
| 16025298 | Background | Brachet C, Vermeulen J, Heinrichs C. Children's virilization and the use of a testosterone gel by their fathers. Eur J Pediatr. 2005 Oct;164(10):646-7. doi: 10.1007/s00431-005-1714-z. Epub 2005 Jul 16. |
| 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. |
| Background | 1. Plymate SR "Male Hypogonadism" in Principles and Practice of Endocrinology and Metabolism (3rd. Ed). Ed. Kenneth Becker, pp:1125-1150 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Body Weight | Mean | Standard Deviation | kg |
|
| Follicle-stimulating hormone (FSH) | Mean | Standard Deviation | IU/L |
|
| Luteinizing hormone (LH) | Mean | Standard Deviation | IU/L |
|
| Testosterone | Mean | Standard Deviation | ng/dL |
|
| Prostate-specific antigen (PSA) | Mean | Standard Deviation | ng/mL |
|
|
|
| Primary | Mean Testosterone Concentration | initial 24-hour pharmacokinetics (PK) of oral testosterone dosed 3 times daily and post 24-hour PK after 9 days of treatment | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Maximum Dihydrotestosterone (DHT) Concentration | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Mean Dihydrotestosterone (DHT) Concentration | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Maximum Sex Hormone-Binding Globulin (SHGB)Concentration | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Mean SHGB Concentration | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Maximum Estradiol Concentration | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Mean Estradiol Concentration | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Free T Maximum Concentration | Free T normal range 4.7-18 ng/dL | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| Secondary | Free Testosterone Mean Concentration | Free T normal range 4.7-18 ng/dL | per protocol | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/dL | baseline & day 9 |
|
|
|
| 0 |
| 12 |
| 8 |
| 12 |
| Headache | General disorders | Systematic Assessment |
|
| upper respiratory infection | Infections and infestations | Systematic Assessment |
|
| confusion | General disorders | Systematic Assessment | transient episode likely due to heat exposure |
|
| musculoskeletal injury | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| elevated serum aspartate aminotrasferase | Investigations | Systematic Assessment | day 4 of treatment |
|
| elevated serum alanine aminotransferase | Investigations | Systematic Assessment | day 4 of treatment |
|
| elevated serum bilirubin | Investigations | Systematic Assessment | day 4 of treatment |
|
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| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |