ORAL T-6: Oral Androgens in Man-6 - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Pharmacokinetics Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Contraception Hypogonadism
Interventions:	Drug: Acyline Drug: Testosterone Drug: Finasteride

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were recruited through news media (newspaper, website) and college campus bulletin boards in Seattle WA, between April 2008-March 2009.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
19 participants recruited; 19 screened, 2 excluded.

Reporting Groups

Description

Testosterone Only

(Day 1) Acyline 300 mcg/kg once, followed 24 hours later (Day 2) by "immediate release" T 300 mg po once (as a control), followed 24 hours later (Day 3) by "external matrix fast release" T 300 mg once, followed 24 hours later (Day 4) by "external matrix slow release" T 300 mg once, followed 96 hours later (Day 8) by "immediate release" T 600 mg, followed 24 hours later (Day 9) by "external matrix fast release" T 600 mg po once, followed 48 hours later (Day 11) by "external matrix slow release" T 600 mg once.

Testosterone Plus Finasteride

(Day -2 to Day 12) 1 mg Finasteride PO once daily for 14 days total. (Day 1) Acyline 300 mcg/kg once, followed 24 hours later (Day 2) by "immediate release" T 300 mg po once (as a control), followed 24 hours later (Day 3) by "external matrix fast release" T 300 mg once, followed 24 hours later (Day 4) by "external matrix slow release" T 300 mg once, followed 96 hours later (Day 8) by "immediate release" T 600 mg, followed 24 hours later (Day 9) by "external matrix fast release" T 600 mg po once, followed 48 hours later (Day 11) by "external matrix slow release" T 600 mg once.

Participant Flow: Overall Study

	Testosterone Only	Testosterone Plus Finasteride
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

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Reporting Groups

	Description
Testosterone Only	(Day 1) Acyline 300 mcg/kg once, followed 24 hours later (Day 2) by "immediate release" T 300 mg po once (as a control), followed 24 hours later (Day 3) by "external matrix fast release" T 300 mg once, followed 24 hours later (Day 4) by "external matrix slow release" T 300 mg once, followed 96 hours later (Day 8) by "immediate release" T 600 mg, followed 24 hours later (Day 9) by "external matrix fast release" T 600 mg po once, followed 48 hours later (Day 11) by "external matrix slow release" T 600 mg once.
Testosterone Plus Finasteride	(Day -2 to Day 12) 1 mg Finasteride PO once daily for 14 days total. (Day 1) Acyline 300 mcg/kg once, followed 24 hours later (Day 2) by "immediate release" T 300 mg po once (as a control), followed 24 hours later (Day 3) by "external matrix fast release" T 300 mg once, followed 24 hours later (Day 4) by "external matrix slow release" T 300 mg once, followed 96 hours later (Day 8) by "immediate release" T 600 mg, followed 24 hours later (Day 9) by "external matrix fast release" T 600 mg po once, followed 48 hours later (Day 11) by "external matrix slow release" T 600 mg once.
Total	Total of all reporting groups

Baseline Measures

	Testosterone Only	Testosterone Plus Finasteride	Total
Number of Participants [units: participants]	8	8	16
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	8	8	16
>=65 years	0	0	0
Gender [units: participants]
Female	0	0	0
Male	8	8	16
Region of Enrollment [units: participants]
United States	8	8	16
Body Mass Index (BMI) [units: kg/m^2] Mean ± Standard Deviation	26 ± 4	28 ± 8	27 ± 4
Estradiol [units: pmol/L] Mean ± Standard Deviation	70.1 ± 16.1	114 ± 54	92.0 ± 35.0
Height [units: centimeters] Mean ± Standard Deviation	178 ± 5	179 ± 7	178.5 ± 6
Sex Hormone Binding Globulin (SHBG) [units: nmol/L] Mean ± Standard Deviation	35.5 ± 12.8	32.5 ± 19.6	34 ± 16.2
Testosterone (T) [units: nmol/L] Mean ± Standard Deviation	14.5 ± 2.5	16.8 ± 8.9	15.65 ± 5.7
Weight [units: kilogram] Mean ± Standard Deviation	83 ± 18	89 ± 22	86 ± 20

Outcome Measures

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1. Primary:

Area Under the Curve-Serum T [ Time Frame: 14 days ]

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Measure Type	Primary
Measure Title	Area Under the Curve-Serum T
Measure Description	No text entered.
Time Frame	14 days
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

Description

Testosterone Only

(Day 1) Acyline 300 mcg/kg once, followed 24 hours later (Day 2) by "immediate release" T 300 mg po once (as a control), followed 24 hours later (Day 3) by "external matrix fast release" T 300 mg once, followed 24 hours later (Day 4) by "external matrix slow release" T 300 mg once, followed 96 hours later (Day 8) by "immediate release" T 600 mg, followed 24 hours later (Day 9) by "external matrix fast release" T 600 mg po once, followed 48 hours later (Day 11) by "external matrix slow release" T 600 mg once.

Testosterone Plus Finasteride

(Day -2 to Day 12) 1 mg Finasteride PO once daily for 14 days total. (Day 1) Acyline 300 mcg/kg once, followed 24 hours later (Day 2) by "immediate release" T 300 mg po once (as a control), followed 24 hours later (Day 3) by "external matrix fast release" T 300 mg once, followed 24 hours later (Day 4) by "external matrix slow release" T 300 mg once, followed 96 hours later (Day 8) by "immediate release" T 600 mg, followed 24 hours later (Day 9) by "external matrix fast release" T 600 mg po once, followed 48 hours later (Day 11) by "external matrix slow release" T 600 mg once.

Measured Values

	Testosterone Only	Testosterone Plus Finasteride
Number of Participants Analyzed [units: participants]	8	8
Area Under the Curve-Serum T [units: nmol*h/L] Mean ± Standard Error
external matrix 'immediate' release	143 ± 47	198 ± 86
external matrix 'fast' release	144 ± 44	384 ± 273
external matrix 'slow' release	162 ± 60	237 ± 141

Statistical Analysis 1 for Area Under the Curve-Serum T

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Wilcoxon sign-rank
P Value ^[4]	<0.05

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	A sample size of 8 per group was estimated to confer an 80% power to detect a 40% difference in testosterone AUC with a standard deviation of 20% at an alpha of 0.05
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

2. Secondary:

Area Under the Curve-serum DHT [ Time Frame: 14-days ]

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3. Secondary:

Area Under the Curve-E2 [ Time Frame: 14 Days ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: John K Amory, MD, MPH
Organization: University of Washington
phone: 206-616-1727
e-mail: jamory@u.washington.edu

Publications of Results:

Snyder CN, Clark RV, Caricofe RB, Bush MA, Roth MY, Page ST, Bremner WJ, Amory JK. Pharmacokinetics of Two Novel Formulations of Modified Release Oral Testosterone Alone and with Finasteride in Normal Men with Experimental Hypogonadism. J Androl. 2010 May 13; [Epub ahead of print]

Other Publications:

Plymate SR "Male Hypogonadism" in Principles and Practice of Endocrinology and Metabolism (3rd. Ed). Ed. Kenneth Becker, pp:1125-1150

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.

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.

Responsible Party:	John K Amory, MD, MPH, University of Washington
ClinicalTrials.gov Identifier:	NCT00663793 History of Changes
Other Study ID Numbers:	33738-B, U54HD42456-06, K23 HD045386
Study First Received:	April 18, 2008
Results First Received:	June 25, 2010
Last Updated:	December 27, 2010
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

ORAL T-6: Oral Androgens in Man-6 (ORAL-T-6)