Efficacy Study for Use of Dutasteride (Avodart) With Testosterone Replacement

Termination criteria

• Serum AST or ALT > 3 times ULN
• Total serum bilirubin > 1.5 times ULN

• no study termination of a patient with documented Gilberts disease for an isolated bilirubin elevation unless it exceeds 2.5x the upper limit of normal.
• Hematocrit > 55%
• Subject experiences any unacceptable or intolerable adverse effect.
• Subject is non-compliant with the study protocol.
• Subject needs to take any medication that would interfere with study measurements
• Subject develops prostate or breast cancer

Inclusion criteria

• Subjects currently on stable testosterone replacement therapy for 3 months' duration using either the approved transdermal products Androgel® or Testim®, or injections of testosterone enanthate or cypionate with a morning serum testosterone concentration within the normal range (300 - 1000 ng/dl). These will dispensed either by prescription or for injections by the PI or co-PI in the office.
• Total Serum PSA >1.5 - 10 ng/mL

• If the total serum PSA is >4ng/mL, the investigator, or a qualified urologist, will perform a 12-core prostate biopsy prior to entry unless such a biopsy has already been performed within the past 6 months.
• If the PSA rises above 4 during any time of the study, the patient will be referred to urology for biopsy.
• Patients with any suspicious rise in PSA of >1.0 ng/ml/yr will have a repeat PSA performed within one month of the original value. If the rise in PSA remains >1.0 ng/ml/yr, the patient will undergo a prostate biopsy.
• b. If the individual has had a negative biopsy more than 6 months previously, with documentation of stable PSA since that time, ie, no sustained increase >1.0ng/ml.
• Subject is able to read and comprehend the informed consent document.
• If the subject is on current replacement therapy for hypopituitarism or other multiple endocrine abnormalities, the subject must be on stable doses of thyroid hormone and/or adrenal replacement hormones for at least 14 days prior to enrollment.

Exclusion criteria

• Use of medications including those interactive with dutasteride from prior studies
• Hematocrit greater than 51%
• Prostate cancer in men found to have a prostate nodule on initial exam and subsequent positive biopsy
• No prostate surgery within 2 months of entry
• No prior use of finasteride, dutasteride within 6 months prior
• A history of hepatic impairment or abnormal liver function tests (defined as ALT, AST, alkaline phosphatase or bilirubin >1.5 times the upper limit of normal) with the exception that bilirubin elevations up to 2.0 times the upper limit of normal in the presence of normal liver enzymes will be permitted in patients with documented Gilbert's Disease. Subjects with Gilbert's disease not to be excluded.
• No serum creatinine greater than 2.0 times upper limit of normal
• No history of alcohol abuse with last 12 months
• Has received any medication in a clinical trial within 2 months of enrollment
• Use of anti-androgens, estrogens or coumadin
• A history or evidence of newly discovered prostate cancer (e.g. positive biopsy or ultrasound, suspicious DRE). In patients with suspicious ultrasound or DRE, including patients with a focal nodule, biopsy shall be performed by a qualified urologist upon study entry unless one was performed and found to be negative within the preceding 6 months.
• History of or current prostate or breast cancer
• Baseline EKG with clinically significant abnormal rhythm or abnormal QT interval
• Systolic blood pressure above 170mmHg or diastolic blood pressure above 90 mm Hg on baseline physical exam
• Clinically significant peripheral edema on baseline physical exam
• History of sleep apnea
• History of psychiatric disorders or major depression
• Consumption of grapefruit juice within 7 days of enrollment or is unwilling to eliminate use of grapefruit juice during the study period
• History of allergy to study medication
• Hemoglobin A1c > 9% in a non-insulin dependent diabetic
• Subjects with abnormal thyroid function
• Subjects with significantly elevated triglycerides