A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Dutasteride in Extending the Time to Progression of Low-Risk, Localized Prostate Cancer in Men Who Are Candidates for or Undergoing Expectant Management

Inclusion Criteria

Inclusion criteria:

- Must be male ≥48 and ≤82 years of age

- Have biopsy proven, low-risk, localized prostate cancer and active in expectant
management not more than 14 months. [For the purposes of assessing subject
eligibility a diagnostic biopsy must have included at least 10 cores, (< 4 cores
positive and <50% of any one core positive) and must have been obtained within 8
months of screening]. If a saturation biopsy was performed (20 or more cores
obtained) 2-3 cores are to be positive for prostate cancer and with <50% of any one
core positive. Initial diagnosis of T1a/T1b obtained during a Transrectal ultrasound
(TURP) is not allowed.

- Gleason score ≤6 [Gleason pattern 4 or above must not be present on any biopsy
(initial or entry)]

- Clinical stage T1c-T2a

- Serum Prostate Specific Antigen (PSA) ≤11ng/mL. If the screening PSA value from the
central laboratory is greater than 11ng/ml, one PSA retest is allowed through the
central laboratory

- A life expectancy greater than five years.

- Able to swallow and retain oral medication

- Able and willing to participate in the full 3 years of the study

- Able to read and write (health outcomes questionnaires are self-administered),
understand instructions related to study procedures and give written informed
consent.

Exclusion criteria:

- Subject has ever been treated for prostate cancer with any of the following:

- Radiotherapy (external beam or brachytherapy)

- Chemotherapy

- Hormonal therapy (e.g., megestrol, medroxyprogesterone, cyproterone,
diethylstilbestrol (DES)

- Oral glucocorticoids

- Gonadotropin-releasing hormone (GnRH) analogues (e.g., leuprolide, goserelin)

- Glucocorticoids, except inhaled or topical, are not permitted within 3 months prior
to visit one

- Current and/or previous use of the following medications:

- Finasteride (Proscar, Propecia), or Dutasteride (GI198745, AVODART) exposure within 6
months prior to study entry are excluded.

- Any other investigational 5α-reductase inhibitors within the past 12 months.

- Anabolic steroids (subject must discontinued for 6 months prior to study entry to be
eligible)

- Drugs with antiandrogenic properties within the past 6 months (e.g,. spironolactone,
flutamide, bicalutamide, *cimetidine, *ketoconazole, metronidazole, progestational
agents) NOTE: Use of dietary and herbal supplements (e.g., selenium, Vitamin E, saw
palmetto) during the study is discouraged but not prohibited. All dietary and herbal
supplement usage will be recorded in the case report form (CRF).

*The use of cimetidine is permitted prior to study entry. The use of topical
ketoconazole is permitted prior to and during the study.

- Prostate volume >80 cc

- Subject has had prior prostatic surgery including Transurethral needle ablation of
the prostate (TUNA), TURP, Transurethral incision of the prostate (TUIP), laser
treatment, thermotherapy, balloon dilatation, prosthesis, and ultrasound ablation
within 3 months of enrolment

- Severe Benign Prostatic Hyperplasia (BPH) symptoms as manifested by International
Prostate Symptom Score (IPSS) symptom score (calculated using the first 7 questions
only) of ≥25 or >20 if already on alpha blocker therapy.

- Participation in any investigational or marketed drug trial within the 30 days prior
to the first dose of study drug or anytime during the study period.

- Any unstable serious co-existing medical condition(s) including but not limited to
myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias,
clinically evident congestive heart failure, or cerebrovascular accident within 6
months prior to Screening visit; uncontrolled diabetes or peptic ulcer disease which
is uncontrolled by medical management.

- Abnormal liver function test (greater than 2 times the upper limit of normal for
alanine aminotransferase [ALT], aspartate aminotransferase [AST], or alkaline
phosphatase [ALP]); or bilirubin >1.5 times the upper limit of normal.

- Serum creatinine >1.5 times the upper limit of normal.

- History of another malignancy within five years that could affect the diagnosis of
prostate cancer.

- History or current evidence of drug or alcohol abuse within the last 12 months.

- History of any illness (including psychiatric) that, in the opinion of the
investigator, might confound the results of the study or pose additional risk to the
subject.

- Known hypersensitivity to any 5α-reductase inhibitor or to any drug chemically
related to dutasteride.