Clinical trial NCT00603187: ACY-7 Oral Administration of Acyline
Official title: Oral Administration of the GnRH Antagonist Acyline in Normal Men Part II: Multiple-dose Pharmacokinetics (Acyline-7/MER 104-02)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy
Keywords: Male Contraception
Acyline
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Merrion Pharmaceuticals, LLC
First posted: 2008-01-28
Enrollment: 4
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: We propose oral dosing of gastrointestinal permeation enhancement technology \[GIPET\] enhanced oral acyline at 20 mg everyday for one week to determine the steady-state (multiple-dose) pharmacokinetics of oral acyline in four normal, healthy young men.

Detailed description: The purpose of this study is to test how the body responds to a new oral form of acyline given for seven days and to also look at the safety of oral acyline.

Acyline temporarily blocks the production of the hormone testosterone in healthy men. It has been tested in over 100 men in an injection form. This study will be testing acyline in a pill form for seven days.

This study may help develop an oral form of testosterone-blocker which may be useful in the treatment of diseases such as prostate cancer, premature puberty and possibly in a male contraceptive.

This study will evaluate a single dose of oral acyline given once a day for seven days and subsequent effects on Testosterone, FSH and LH blood serum concentrations.

Eligibility criteria: Inclusion Criteria:

* Healthy male
* 18-50 years of age
* Non-smoker
* Not taking any medications other than the study drug for the duration of the study.
* Must be willing to use an accepted method of contraception during the study.

Exclusion Criteria:

* BMI \> 35
* Abnormal evaluation on screening exam and labs
* Known history of alcohol abuse, illicit drugs or steroids and/or use of more that 3 alcoholic beverages/day
* History of current testosterone use or infertility
* History of testicular disease or severe testicular trauma
* History of major psychiatric disorder or sleep apnea
* History of bleeding disorder or need for anticoagulation
* Current smoker or utilizing nicotine patches or gum
* Participation in a hormonal drug study within past month.

Primary outcomes:
measure: Testosterone Blood Serum Concentration
timeFrame: 7 days
Secondary outcomes:
measure: FSH Blood Serum Concentration
timeFrame: 7 days
measure: LH Blood Serum Concentration
timeFrame: 7 days
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: John K Amory, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1210/jc.2003-032123.
citation: Matthiesson KL, Amory JK, Berger R, Ugoni A, McLachlan RI, Bremner WJ. Novel male hormonal contraceptive combinations: the hormonal and spermatogenic effects of testosterone and levonorgestrel combined with a 5alpha-reductase inhibitor or gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab. 2005 Jan;90(1):91-7. doi: 10.1210/jc.2004-1228. Epub 2004 Oct 27.
citation: 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.
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. doi: 10.2164/jandrol.05058.
citation: Page ST, Lin DW, Mostaghel EA, Hess DL, True LD, Amory JK, Nelson PS, Matsumoto AM, Bremner WJ. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metab. 2006 Oct;91(10):3850-6. doi: 10.1210/jc.2006-0968. Epub 2006 Aug 1.
citation: Page ST, Amory JK, Anawalt BD, Irwig MS, Brockenbrough AT, Matsumoto AM, Bremner WJ. Testosterone gel combined with depomedroxyprogesterone acetate is an effective male hormonal contraceptive regimen and is not enhanced by the addition of a GnRH antagonist. J Clin Endocrinol Metab. 2006 Nov;91(11):4374-80. doi: 10.1210/jc.2006-1411. Epub 2006 Aug 29.