Comparative Efficacy of Dutasteride Plus Tamulosin With Lifestyle Advice Versus Watchful Waiting Plus Lifestyle Advice in the Management of Treatment naïve Men With Moderately Symptomatic Benign Prostatic Hyperplasia and Prostate Enlargement
Condition: Prostatic Hyperplasia
MeSH terms: Prostatic Hyperplasia; Hyperplasia
Intervention: Dutasteride plus tamsulosin; tamsulosin
Intervention description: Take 1 capsule daily; Take 1 capsule daily when escalation criteria met
Intervention MeSH terms: Tamsulosin; Dutasteride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 742.0
Sex: Male
Minimum age: 50 Years
Healthy volunteers: No

Summary:

      Study FDC114615 is a two year, multi-centre, randomised, open-label trial to assess the
      efficacy of Dutasteride plus tamsulosin when compared to the standard practice of watchful
      waiting, with a defined escalation to tamsulosin in treatment naive men with symptomatic
      benign prostate hyperplasia (BPH).

      Once consented, each subject will undergo screening procedures to ensure the prostate volume
      and post void residual are within eligible range. If all entry criteria are met, subjects
      will be randomised (1:1) to receive Dutasteride plus tamsulosin with lifestyle advice or
      watchful waiting, with lifestyle advice, with a defined escalation to tamsulosin. Escalation
      will be initiated when no improvement from baseline is scored using the International
      Prostate Symptom Score (version 2) (IPSS) questionnaire.

      After randomisation, the subjects return to site at one month, then every 13 weeks until two
      years of treatment is complete or they are withdrawn. Key assessments, such as Adverse Events
      (AE's) and concomitant medication monitoring and completion of the quality of life
      questionnaires are performed at each visit and the data recorded.
    

Eligibility criteria:

        -  Males aged ≥50 years.

          -  A confirmed clinical diagnosis of BPH.

          -  International Prostate Symptom Score (IPSS) 8-19 at Visit 1 (screening).

          -  Prostate volume ≥30 cc (by transrectal ultrasonography; TRUS).

          -  Total serum prostate specific antigen (PSA) ≥1.5 ng/mL at Visit 1 (screening).

          -  Willing and able to give signed 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 and BII questionnaires.

          -  Able to swallow and retain oral medication.

          -  Willing and able to participate in the study for the full 2 years.

          -  Men with a female partner of childbearing potential must either agree to use effective
             contraception or have had a prior vasectomy. Contraception must be used from 2 weeks
             prior to administration of the first dose of study treatment until at least 5
             half-lives for the drug plus 3 months to allow clearance of any altered sperm after
             the last dose of study treatment.

          -  French subjects: In France, a subject will be eligible for inclusion in this study
             only if either affiliated to or a beneficiary of a social security category.

        Note: If total serum PSA is >4 ng/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 Digital rectal examination (DRE), review TRUS
        taken within previous month, consider 8-12 core prostate biopsy in accordance with routine
        clinical practice

        Exclusion Criteria:

          -  Subjects meeting any of the following criteria must not be enrolled in the study:

          -  Total serum PSA >10.0 ng/mL at Visit 1 (screening).

          -  History or evidence of prostate cancer (e.g. positive biopsy or ultrasound within the
             previous 6 months, suspicious DRE and/or rising PSA).

        Excluded medication and therapies Current or any prior use of the following prohibited
        medications

          -  a 5α-reductase inhibitor (finasteride or dutasteride),

          -  anti-cholinergics (e.g. oxybutynin, propantheline)

          -  an alpha-adrenoreceptor blocker (i.e. indoramin, prazosin, terazosin, tamsulosin,
             alfuzosin and doxazosin) for BPH or Lower urinary tract symptoms (LUTS)

          -  any drugs with anti-androgenic properties (e.g. spironolactone, flutamide,
             bicalutamide, cimetidine, ketoconazole, progestational agents) within the previous 6
             months.

          -  any drugs noted for gynaecomastia effects, or could affect prostate volume, within 6
             months of the Visit 1

          -  any investigational or marketed study drug within 30 days or 5 half-lives, (whichever
             is longer), preceding the first dose of study treatment.

        Current use of:

          -  any alpha-adrenoreceptor blocker (i.e. indoramin, prazosin, terazosin, tamsulosin,
             alfuzosin and doxazosin)

          -  anabolic steroids.

          -  drugs known or thought to have an interaction with tamsulosin, e.g. cimetidine and
             warfarin.

          -  Use of phytotherapy for BPH within 2 weeks prior to Visit 1 (screening) and/or
             predicted to need phytotherapy during the study.

        Have a known (immediate or delayed) hypersensitivity reaction or idiosyncrasy to drugs
        chemically related to the study medication or excipients that, in the opinion of the
        Investigator or GlaxoSmithKline contraindicates their participation.

        Recent Medical Procedures

          -  Previous prostatic surgery (including TURP, balloon dilatation, thermotherapy and
             stent replacement) or other invasive or minimally invasive procedures to treat BPH.

          -  History of flexible/rigid cystoscopy or other instrumentation of the urethra within 7
             days prior to Visit 1 (screening). Catheterisation (<10F) is acceptable with no time
             restriction.

        Medical history

          -  History of AUR within 3 months prior to Visit 1 (screening).

          -  Post-void residual volume >250 mL (suprapubic ultrasound) at Visit 1 (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 'first dose' hypotensive episode on initiation of alpha-1-adrenoreceptor
             antagonist therapy for hypertension.

          -  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 breast cancer or clinical breast examination finding of unclear origin or
             suggestive of malignancy.

          -  History of hepatic impairment or abnormal liver function tests at Visit 1 (screening).
             (defined as Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) or
             alkaline phosphatase >2 times the Upper limit of normal (ULN) , or total bilirubin
             >1.5 times the ULN, (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 at Visit 1 (screening)..

          -  Prior history of malignancies (other than basal cell carcinoma or squamous cell
             carcinoma of the skin) within the past 5 years. Subjects who have had no evidence of
             the malignancy for ≥5 years are eligible.

          -  History of any illness (including psychiatric) that in the opinion of the investigator
             might confound the results of the study or poses additional risk to the subject.

          -  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 or current evidence of drug or alcohol abuse within the previous 12 months.

          -  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 the study procedures, in the opinion of the Investigator or GSK Medical
             Monitor.