Pharmacokinetic Study of Single Dose Dutasteride in Healthy Subjects - Full Text View

Sponsor:	University of Connecticut Health Center
Collaborators:	National Institutes of Health (NIH) National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by:	University of Connecticut Health Center
ClinicalTrials.gov Identifier:	NCT00802321

Purpose

To monitor the inhibition of 5a-reductase (5AR) enzyme activity at 1, 3, 7, 14, 21, 28 and 42 days following administration of a single dose of dutasteride (2, 3, or 4 mg) by measuring the change in blood levels of 3a-androstanediol glucuronide (3a-diolG) and the ratio of dihydrotestosterone (DHT) to testosterone. To accomplish this aim, an open-label, between-subjects dose comparison study design will be employed with subjects receiving a 2, 3, or 4 mg dosage. Subjects (up to n=40 enrolled to allow a minimum of 24 completers) will be randomly assigned to one of the 3 dose levels. Results of this study will inform the dose selection for a subsequent placebo-controlled, within-subject, crossover study of dutasteride on the effects of alcohol.

A secondary aim of this study is to examine the correlation of a genetic variation in the type I 5AR gene and baseline DHT/T ratio and effect of dutasteride at day 3. A variation in this gene which is one of the targets of dutasteride has been reported to be associated with higher baseline levels of DHT.

Condition	Intervention
Alcohol Related Disorders Alcoholism Alcohol Abuse	Drug: Dutasteride

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver)
Official Title:	Pharmacokinetic Study of Single Dose Dutasteride in Healthy Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Alcoholism

Drug Information available for: Dutasteride

U.S. FDA Resources

Further study details as provided by University of Connecticut Health Center:

Primary Outcome Measures:

Change in 5AR enzyme activity as measured by the DHT/testosterone ratio and levels of 3a-androstanediol glucuronide as a function of time after a single loading dose of dutasteride. [ Time Frame: 1-42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary outcomes include the moderating effect of genetic variation in type I 5AR enzyme on DHT levels and any effects of dutasteride on subjects self report of alcohol use in their everyday life. [ Time Frame: 1-42 days ] [ Designated as safety issue: No ]

Enrollment:	40
Study Start Date:	April 2006
Study Completion Date:	November 2006
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: dutasteride	Drug: Dutasteride Subjects will receive a single dose of 2, 3 or 4 mg of dutasteride based on random assignment. Other Name: Avodart

Detailed Description:

Alcohol abuse and dependence remain important public health problems. The chemical mechanisms by which alcohol affects the nervous system are not well understood. Recent theories suggest that alcohol stimulates release of "neuroactive" steroid hormones which are important mediators of alcohol effects. This proposal seeks to identify the most appropriate dosage of an FDA approved medication, dutasteride, which blocks the metabolism of steroid hormones, so that we can use dutasteride as a pharmacologic probe of the biochemistry of alcohol effects in human subjects in a subsequent study.

Eligibility

Ages Eligible for Study:	21 Years to 55 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Subjects will be healthy males volunteers who are 21-55 years old and have a BMI >18.5 and <32.5. All enrolled subjects will have signed IRB approved consent.

Exclusion Criteria:

Subjects cannot have a current or past DSM-IV diagnosis of alcohol or drug dependence, current or past 12-months diagnosis of alcohol or drug abuse or major psychiatric disorder, neurological illness, have had a hypersensitivity reaction to dutasteride, physical exam evidence of liver dysfunction, currently be using psychotropic medications or medications that are known to influence steroid hormone levels or metabolism. Nicotine-dependent subjects will be excluded to avoid the confounding effects of nicotine withdrawal during day-long laboratory sessions which are part of the planned alcohol administration study as well as effects of tobacco use on metabolism. Subjects who do not agree to use barrier contraception for 1 week after administration of dutasteride will be excluded

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00802321

Locations

United States, Connecticut
Unversity of Connecticut Health Center
Farmington, Connecticut, United States, 06030

Sponsors and Collaborators

University of Connecticut Health Center

National Institutes of Health (NIH)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

Principal Investigator:

Jonathan Covault, M.D, Ph.D

University of Connecticut Health Center

More Information

No publications provided

Responsible Party:	Jonathan Covault, M.D., Ph.D., University of Connecticut Health Center
ClinicalTrials.gov Identifier:	NCT00802321 History of Changes
Other Study ID Numbers:	06-217S-2, 620, 5R01AA015606-02
Study First Received:	December 2, 2008
Last Updated:	September 22, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Connecticut Health Center:

steroid 5AReductase
genetic polymorphism
GABA receptor

Additional relevant MeSH terms:

Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Dutasteride

5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012