Official Title: “An Open Label Study to Investigate the Efficacy and Safety of Treatment With Dutasteride (0.5mg) Once Daily for One Year and 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)”

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 visits)

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2008

Intervention(s) in this Clinical Trial

• Drug: tamsulosin used with dutasteride
  • Dutasteride 0.5mg once daily for one year and tamsulosin 0.4mg administered once daily for 3 months, followed by counseling on flexible dosing of tamsulosin on an as needed basis.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Dutasteride 0.5mg once daily for one year and tamsulosin 0.4mg administered once daily for 3 months, followed by counseling on flexible dosing of tamsulosin on an as needed basis.

Primary Measures

• Symptom Improvement
  • Time Frame: 13 months
    Safety Issue?: No

Secondary Measures

• Health Outcome Measures
  • Time Frame: 13 months
    Safety Issue?: No
• Safety and Tolerability
  • Time Frame: 13 months
    Safety Issue?: Yes
• Economic Impact
  • Time Frame: 13 months
    Safety Issue?: No
• Reduction of AUR and BPH-related Surgery
  • Time Frame: 13 months
    Safety Issue?: No

Inclusion Criteria:

• 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 -

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 (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 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 (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 antagonist therapy.
• 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 this study.
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Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Siami, Paul F., M.D.

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00701779

Study ID Number: Siami104907

ClinicalTrials.gov Identifier: NCT00701779

Health Authority: United States: Institutional Review Board