Study to Compare the Efficacy and Safety of Combination Treatment With Dutasteride and Tamsulosin With Tamsulosin Monotherapy, in Men With Moderate to Severe Benign Prostatic Hyperplasia
Condition: Prostatic Hyperplasia
MeSH terms: Prostatic Hyperplasia; Hyperplasia
Intervention: Dutasteride 0.5mg capsules; Dutasteride placebo capsules; Tamsulosin 0.2mg tablets; Disintegrating placebo tamsulosin tablet
Intervention description: Dutasteride 0.5mg capsules will be supplied as plain, oblong, opaque, dull yellow soft gelatin capsules.; Dutasteride placebo will be supplied as plain, oblong, opaque, dull yellow soft gelatin capsules.; Commercially available tamsulosin 0.2mg tablets will be supplied.; Disintegrating placebo tamsulosin tablet will be supplied for the run-in period.
Intervention MeSH terms: Tamsulosin; Dutasteride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 607.0
Sex: Male
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Benign Prostatic Hyperplasia; Quality of Life

Summary:

      This is a multicentre, randomised, double-blind, parallel group study in Asian subjects. The
      aim of the study is to investigate whether combination therapy with dutasteride and
      tamsulosin is more effective than tamsulosin monotherapy for the improvement of symptoms and
      health outcomes in an at risk population of benign prostatic hyperplasia (BPH) clinical
      progression including older men (>=50 years), with moderate-severe symptoms of BPH, enlarged
      prostates (>=30 cubicentimeter [cc]) and prostate specific antigen (PSA) >= 1.5 nanograms per
      milliliter (ng/mL). Each subject who met the eligibility criteria at screening will enter a
      four-week single-blind, placebo run-in period following which each subject will be randomised
      into a 2 year double-blind treatment phase. The total study duration for each subject will be
      up to 110 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 TRUS)

          -  Total serum Prostate Specific Antigen (PSA) >=1.5ng/mL and <= 10 ng/mL at Screening

          -  Maximum urinary flow rate (Qmax) >5mL/sec and 15mL/sec and minimum voided volume of
             >=125 milliliter (mL) at Screening

          -  Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2x upper limit of
             normal (ULN); alkaline phosphatase and bilirubin <= 1.5xULN (isolated bilirubin >
             1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

          -  Fluent and literate in local language with the ability to comprehend and record
             information on the IPSS, BPH-related Health Status (BHS), BPH Impact Index (BII), and
             Problem Assessment Scale Sexual Function Inventory (PAS- SFI) questionnaires

          -  Men with a female partner of childbearing potential must agree to use a condom up to 6
             months after the last dose (applies only to countries where the local product
             monograph for dutasteride mandates condom use for men with a female partner of
             childbearing potential)

        Exclusion Criteria:

          -  History or evidence of prostate cancer (e.g. positive biopsy or ultrasound, suspicious
             Digital Rectal Examination [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, including consideration of prostate
             biopsy.

          -  Previous prostatic surgery (including TURP, laser, transrectal high intensity focused
             ultrasounds(HIFU), thermotherapy, transurethral needle ablation (TUNA), balloon
             dilatation, 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. Catheterisation (<10F) 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 conditions 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).

          -  Unstable liver disease (chronic stable hepatitis B and C are acceptable if subject
             meets entry criteria).

          -  History of renal insufficiency, or serum creatinine >1.5 times the upper limit of
             normal at Screening.

          -  Any unstable, serious co-existing medical condition(s) including, but not limited to:

               1. 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.

               2. 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.

               3. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
                  conditions that could interfere with subject's safety, obtaining informed consent
                  or compliance to study procedures in the opinion of the investigator or GSK
                  medical monitor. Investigator may consult with GSK Medical Monitor if condition
                  could interfere with subject's safety

               4. History of breast cancer or clinical breast examination finding suggestive of
                  malignancy.

               5. History of malignancy within the past five years, except for basal cell carcinoma
                  of the skin. Subjects with a priori malignancy who have had no evidence of
                  disease for at least the past 5 years are eligible.

          -  Current or Previous Use of the following medications:

               1. Use of any 5-alpha-reductase inhibitor (e.g. finasteride), any drugs with
                  antiandrogenic properties (e.g. spironolactone, flutamide, bicalutamide,
                  cimetidine, ketoconazole, progestational agents), or other drugs noted for
                  gynaecomastia effects, or that could affect prostate volume, within the 6 months
                  preceding the historical TRUS or Screening Visit and throughout the study (other
                  than as study medication). Previous use of dutasteride should not be within 6
                  months of the baseline or historical TRUS.

               2. Anabolic steroids (subject must discontinue for 6 months prior to study entry to
                  be eligible) and agree not to take them for the duration of the study.

               3. Phytotherapy for BPH within 2 weeks of Screening Visit and/or predicted to need
                  phytotherapy during the study.

               4. Use of any alpha-adrenoreceptor blockers within 2 weeks of Screening Visit (i.e.
                  indoramin, prazosin, terazosin, tamsulosin, alfuzosin, doxazosin, silodosin)
                  and/or predicted to need any alpha blockers other than the study prescribed
                  tamsulosin.

               5. Use of any alpha-adrenoreceptor agonists (e.g. pseudoephedrine, phenylephedrine,
                  ephedrine) or anticholinergics (e.g. oxybutynin,tolterodine, darifenacin,
                  solifenacin,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.

          -  Participation in any investigational or marketed drug trial within 30 days (or 5
             half-lives of drug, whichever is the longer) preceding the Screening Visit and/or
             plans to participate in such a trial during the course of this study.