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

This is an interventional treatment trial for Prostatic Hyperplasia focused on measuring Benign Prostatic Hyperplasia, Quality of Life Read More

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.