Dutasteride and Flex Dose of Tamsulosin on as Needed Basis, to Treat Benign Prostatic Hyperplasia

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 52 Weeks. (Including Screening, (up to 7 clinic visits)

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.

A recently published, landmark study (MTOPS - Medical Therapy of Prostatic Symptoms), co-sponsored by the National Institute of Health and the National Institute of Diabetes, Digestive and Kidney Diseases (NIH-NIDDK), demonstrated that, in selected patients, combination therapy with Doxazosin and Finasteride provided additive symptomatic improvements, reduced the risk of acute urinary retention (AUR) and surgical intervention, and was a more effective treatment for reduction in the overall risk of BPH clinical progression.

The aim of this proposed combination study, in a population of patients at high risk of BPH clinical progression, is to investigate whether combination therapy with Dutasteride and Tamsulosin with the subsequent withdrawal of Tamsulosin can maintain superior symptom improvement. At each scheduled visit (3, 6, and 9 months), the subject will be counseled on withdrawal of Tamsulosin. We hypothesize that patients may start with a combination of Dutasteride and Tamsulosin and eventually may be able to eliminate the use of Tamsulosin and maintain acceptable urinary symptoms on Dutasteride alone.

Eligibility Criteria:
Inclusion Criteria:

1. Male ≥50 yrs
2. Diagnosed BPH by medical history and physical examination, including a digital rectal examination
3. International Prostate Symptom Score ≥12 points at Screening
4. Prostate volume ≥30cc (by transrectal ultrasonography; TRUS)
5. Total serum Prostate Specific Antigen ≥1.5 ng/mL at Screening
6. Maximum flow rate ≥5 mL/sec and ≤15 mL/sec and minimum voided volume of ≥125 mL at Screening (based on two voids)
7. Able to give written informed consent and comply with study procedures
8. 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. Able to participate for study duration

Exclusion Criteria:

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
3. Previous prostatic surgery 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 restriction.
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
8. History of breast cancer or clinical breast examination finding of unclear origin or suggestive of malignancy
9. Use of 5 alpha-reductase inhibitor, any drugs with antiandrogenic properties, or drugs noted for gynecomastia effects, within past 6 months and throughout the study. Previous use of AVODART 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
12. Use of any alpha-adrenoreceptor blockers within 2 weeks of Screening
13. Use of any alpha-adrenoreceptor agonists, anticholinergics or cholinergics 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 interaction with Tamsulosin.
16. History of hepatic impairment, abnormal liver function at Screening, History of renal insufficiency, serum creatinine \>1.5 times the upper limit

18. 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 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) 21. History of postural hypotension, dizziness, vertigo, or any other signs and symptoms of orthostasis.

22. History of 'first dose' hypotensive episode on initiation of alpha-l-adrenoreceptor antagonist therapy.

23. History of unsuccessful treatment with finasteride or Dutasteride 24. History or current 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 this study.