Official Title: “See Detailed Description”

This study will investigate the efficacy and safety of treatment with dutasteride and tamsulosin, administered once daily for 4 years, alone and in combination, on the improvement of symptoms and clinical outcome in men with moderate to severe symptomatic Benign Prostatic Hyperplasia (BPH). Study visits are every 3 months for up to 4 years (18 clinic visits).

Transrectal ultrasound (TRUS) is done annually.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2009

A randomised, double-blind, parallel group study to investigate the efficacy and safety of treatment with Dutasteride (0.5mg) and Tamsulosin (0.4mg), administered once daily for 4 years, alone and in combination, on the improvement of symptoms and clinical outcome in men with moderate to severe symptomatic benign prostatic hyperplasia.

Intervention(s) in this Clinical Trial

• Drug: AVODART
• Drug: Tamsulosin

Primary Measures

• Efficacy of combination treatment in the symptomatic improvement of BPH after 2 years of treatment. Efficacy of combination treatment in the clinical outcomes of AUR or BPH-related surgery after 4 years.
  • Time Frame: 2 years
    

Secondary Measures

• Efficacy of combination treatment in the reduction of risk for BPH clinical progression after 4 years. Effects of combination therapy,on health outcome measures. Safety and tolerability.
  • Time Frame: 4 years
    

Inclusion criteria:

• A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:
• males, aged ≥50 years
• clinical diagnosis of BPH by medical history and physical examination, including a digital rectal examination (DRE)
• International Prostate Symptom Score (IPSS) ≥12 points at Screening
• prostate volume ≥30cc (by transrectal ultrasonography; TRUS)
• total serum Prostate Specific Antigen (PSA) ≥1.5ng/mL at Screening
• maximum flow rate (Qmax) >5mL/sec and ≤15mL/sec and minimum voided volume of ≥125mL at
• Screening (based on two voids)
• willing and able to give written informed consent and comply with study procedures
• fluent and literate in local language with the ability to read, comprehend and record information on the IPSS, BII and Patient Satisfaction questionnaire
• able to swallow and retain oral medication
• willing and able to participate in the study for the full 4 years. End of Required
• Standard Wording.

Insert Inclusion Criteria below:

Exclusion Criteria:

Required Standard Wording:

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:
• total serum PSA >10.0ng/mL at Screening
• history or evidence of prostate cancer (e.g. positive biopsy or ultrasound, suspicious
• DRE). Patients with suspicious ultrasound or DRE who have had a negative biopsy within the preceding 6 months and stable PSA are eligible for the study.
• Note: If total serum PSA is >4ng/mL and unless PSA value has 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, review TRUS taken within previous month, consider 8-12 core prostate biopsy in accordance with routine clinical practice.
• previous prostatic surgery (including TURP, balloon dilatation, thermotherapy and stent replacement) or other invasive procedures to treat BPH.
• history of flexible/rigid cystoscopy or other instrumentation of the urethra within 7 days prior to the Screening Visit. Routine catheterisation is acceptable with no time restriction.
• history of AUR within 3 months prior to Screening Visit.
• post-void residual volume >250mL (suprapubic ultrasound) at Screening.
• any causes other than BPH, which may in the judgement 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).
• history of breast cancer or clinical breast examination finding of unclear origin or suggestive of malignancy.
• use of any 5-alpha-reductase inhibitor (e.g. Proscar®, Propecia®, Avodart®), any drugs with antiandrogenic properties (e.g. spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, metronidazole, progestational agents), or other drugs which affect prostate volume, within past 6 months of the Screening Visit and throughout the study (other than as study medication).
• concurrent use of anabolic steroids
• use of phytotherapy for BPH within 2 weeks of Screening Visit and/or predicted to need phytotherapy during the study.
• use of any alpha-adrenoreceptor blockers (i.e. indoramin, prazosin, terazosin, tamsulosin, alfuzosin and doxazosin) within 2 weeks of Screening Visit and/or predicted to need any alpha blockers other than tamsulosin during the study.
• Note: the purpose of this criteria is to be able to standardise baseline symptom severity for all enrolled patients prior to randomisation and not to specifically exclude current alpha-adrenoreceptor blocker users from participation in the study.
• use of any alpha-adrenoreceptor agonists (e.g. pseudoephedrine, phenylephrine, ephedrine) or anticholinergics (e.g. oxybutynin, propantheline) or cholinergics (e.g.
• bethanecol chloride) within 48 hours prior to all uroflowmetry assessments.
• hypersensitivity to any alpha-/beta- adrenoreceptor blocker or 5-alpha-reductase inhibitor, or other chemically-related drugs.
• concurrent use of drugs known or thought to have an interaction with tamsulosin, e.g.
• cimetidine and warfarin.
• 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).
• history of renal insufficiency, or serum creatinine >1.5 times the upper limit of normal or serum creatinine ≥1.5mg/dL at Screening.
• prior history of malignancies other than basal cell carcinoma or squamous cell carcinoma of the skin within the past 5 years. Subjects with a priori malignancy who have had no evidence of disease for at least the past 5 years are eligible.
• 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.
• 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.
• 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.
• history of unsuccessful treatment with tamsulosin or 'first dose' hypotensive episode on initiation of alpha-1-adrenoreceptor antagonist therapy.
• history of unsuccessful treatment with finasteride or dutasteride
• history or current evidence of drug or alcohol abuse within the previous 12 months.
• participation in any investigational or marketed drug trial within 30 days (or 5 half-lives whichever is the longer) preceding the Screening Visit and/or during the course of this study.

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: GlaxoSmithKline

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials, MD Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00090103

Study ID Number: ARI40005

ClinicalTrials.gov Identifier: NCT00090103

Health Authority: United States: Food and Drug Administration