This study will investigate the efficacy and safety of treatment with Dutasteride (0. 5mg),
administered once daily for one year in combination with Tamsulosin (0. 4mg), administered
once daily for 3 months, followed by counseling on flexible dosing of Tamsulosin on an as
needed basis, on the improvement of symptoms and clinical outcome in men with moderate to
severe symptomatic benign prostatic hyperplasia (BPH). At each scheduled visit (3, 6, and 9
months), the subject will be counseled on withdrawal of Tamsulosin. After randomization,
study visits are every 13 weeks for up to 53 Weeks. (Including Screening, (up to 7 clinic
Minimum age: 50 Years.
Maximum age: N/A.
1. Males, aged ≥50 years
2. Clinical diagnosis of BPH by medical history and physical examination, including a
digital rectal examination (DRE)
3. International Prostate Symptom Score (IPSS) ≥12 points at Screening
4. Prostate volume ≥30cc (by transrectal ultrasonography; TRUS)
5. Total serum Prostate Specific Antigen (PSA) ≥1. 5 ng/mL at Screening
6. Maximum flow rate (Qmax) ≥5 mL/sec and ≤15 mL/sec and minimum voided volume of ≥125 mL
at Screening (based on two voids)
7. Willing and able to give written informed consent and comply with study procedures
8. Fluent and literate in English language with the ability to read, comprehend, and
record information on the IPSS, BII, and PPSM questionnaires
9. Able to swallow and retain oral medication
10. Willing and able to participate in the study for the full 1 year -
1. Total serum PSA >10. 0 ng/mL at Screening. Patients with total serum PSA >10. 0 ng/mL
may be acceptable for inclusion if the PSA elevation is thought to be due to BPH and
not prostate cancer (by TRUS and biopsies showing no evidence of prostate cancer).
2. History or evidence of prostate cancer (e. g. positive biopsy). Patients with
suspicious ultrasound or DRE who have had a negative biopsy within the preceding 1
year and stable PSA are eligible for the study. Note: If age-adjusted total serum PSA
is above normal upper limits, and unless PSA value has not been stable for at least
the past 2 years, the investigator should make every appropriate effort to exclude the
possibility of prostate cancer, e. g. further DRE, consider prostate biopsy in
accordance with routine clinical practice.
3. Previous prostatic surgery (including TURP, balloon dilatation, thermotherapy and
stent replacement) or other invasive procedures to treat BPH
4. History of flexible/rigid cystoscopy or other instrumentation of the urethra within 7
days prior to Screening. Catheterization (<10F) is acceptable with no time
5. History of AUR within 3 months prior to Screening
6. Post-void residual volume >250mL (suprapubic ultrasound) at Screening
7. Any causes other than BPH, which may in the judgment of the investigator, result in
urinary symptoms or changes in flow rate (e. g. neurogenic bladder, bladder neck
contracture, urethral stricture, bladder malignancy, acute or chronic prostatitis, or
acute or chronic urinary tract infections)
8. History of breast cancer or clinical breast examination finding of unclear origin or
suggestive of malignancy
9. Use of any 5 alpha-reductase inhibitor (e. g. Proscar, Propecia), any drugs with
antiandrogenic properties (e. g. spironolactone, flutamide, bicalutamide, cimetidine,
ketoconazole, progestational agents), or other drugs noted for gynecomastia effects,
or could affect prostate volume, within past 6 months of the historical TRUS or
Screening and throughout the study (other than as study medication). Previous use of
AVODART should not be within 12 months of the baseline or historical TRUS. Chronic use
of Metronidazole is prohibited.
10. Concurrent use of anabolic steroids
11. Use of phytotherapy for BPH within 2 weeks of Screening and/or predicted to need
phytotherapy during the study.
12. Use of any alpha-adrenoreceptor blockers (i. e. Indoramin, Prazosin, Terazosin,
Tamsulosin, Alfuzosin and Doxazosin) within 2 weeks of Screening and/or predicted to
need any alpha blockers other than Tamsulosin during the study. Note: the purpose of
these criteria is to be able to standardize baseline symptom severity for all enrolled
patients prior to randomization and not to specifically exclude current
alpha-adrenoreceptor blocker users from participation in the study.
13. Use of any alpha-adrenoreceptor agonists (e. g. pseudoephedrine, phenyl ephedrine,
ephedrine) or anticholinergics (e. g. oxybutynin, propantheline) or cholinergics (e. g.
bethanecol chloride) within 48 hours prior to all uroflowmetry assessments.
14. Hypersensitivity to any alpha-/beta- adrenoreceptor blocker or 5-alpha-reductase
inhibitor, or other chemically-related drugs.
15. Concurrent use of drugs known or thought to have an interaction with Tamsulosin, e. g.
Cimetidine and Warfarin.
16. History of hepatic impairment or abnormal liver function tests at Screening [defined
as ALT, AST, and/or alkaline phosphatase >2 times the upper limit of normal, or total
bilirubin >1. 5 times the upper limit of normal (unless associated with predominantly
indirect bilirubin elevation or Gilbert's syndrome)].
17. History of renal insufficiency, or serum creatinine >1. 5 times the upper limit of
normal at Screening.
18. Prior history of malignancies other than basal cell carcinoma or squamous cell
carcinoma of the skin within the past 2 years.
19. History of any illness that in the opinion of the investigator might confound the
results of the study or poses additional risk to the patient.
20. 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; uncontrolled diabetes or peptic ulcer disease which is
uncontrolled by medical management.
21. History of postural hypotension, dizziness, vertigo, or any other signs and symptoms
of orthostasis, which in the opinion of the investigator could be exacerbated by
Tamsulosin and result in putting the subject at risk of injury.
22. History of 'first dose' hypotensive episode on initiation of alpha-l-adrenoreceptor
23. History of unsuccessful treatment with finasteride or Dutasteride
24. History or current evidence of drug or alcohol abuse within the previous 12 months.
25. Participation in any investigational or marketed drug trial within 30 days (or 5
half-lives whichever is the longer) preceding Screening and/or during the course of