Prospective Sexual Function Study for BPH Subjects

This is an European double-blind, placebo controlled parallel group comparison of DUODART (fixed dose combination of dutasteride 0.5mg and tamsulosin 0.4mg, one capsule daily) and placebo.

PRIMARY OBJECTIVE:

To assess the change in sexual function from baseline to 1 year in sexually active men with at least moderate BPH who are treated with DUODART, compared to men treated with placebo .

This is an European double-blind, placebo controlled parallel group comparison of DUODART (fixed dose combination of dutasteride 0.5mg and tamsulosin 0.4mg, one capsule daily) and placebo. Men eligible at screening will be randomised, after a 4 week placebo run-in, to the 2 treatment groups in a 1:1 ratio. All men will receive standardised lifestyle advice (primarily concerning weight management and exercise) relevant to maintaining sexual function. Men will also receive a standardised lifestyle advice leaflet for BPH. The double blind phase will continue for 12 months, with assessment visits at 2 weeks and at months 1, 3, 6, 9 and a final visit at month 12. Subjects with sexual adverse events during the double blind phase will continue to be followed at scheduled study visits until resolution of the adverse event or at a visit 6 months after the last dose of study medication, whichever is sooner.

PRIMARY OBJECTIVE:

To assess the change in sexual function from baseline to 1 year in sexually active men with at least moderate BPH (international prostate symptom score - IPSS = or \> 12) who are treated with DUODART, compared to men treated with placebo . Change in sexual function will be assessed by change in total score from the full men's sexual health questionnaire (MSHQ) which has domains for erectile dysfunction, ejaculatory function and libido.

Eligibility Criteria:
Inclusion Criteria:

* Males aged ≥50 years.
* Men must be sexually active. A man is considered sexually active if he has been engaged in sexual activity with a partner during the past 4 weeks (at least once) and plans to be active during the next 4 weeks (unless due to travel or other practical reasons). Men should confirm that they are in a stable relationship and expect to maintain their sexual activity over the next year.
* A confirmed clinical diagnosis of BPH.
* International Prostate Symptom Score (IPSS) ≥12 at Visit 1 (screening), with bother score 4 or less (score from the IPSS Quality of Life question 8).
* Prostate volume ≥30 cc (by transrectal ultrasonography; TRUS). Measurement should be available by the baseline visit and should have been made /arranged at the screening visit or within the previous 6 months.
* Total serum prostate specific antigen (PSA ≥1.5 ng/mL (see exclusion criteria 1) at Visit 1 (screening).
* Willing and able to give signed written informed consent and comply with study procedures, including the ability to participate in the study for the full 1 year (or 18 months if necessary because of a persistent sexual AE).
* Fluent and literate in local language with the ability to read, comprehend and record information on the MSHQ, IPSS, PPSM, BPH Impact Index (BII) and C-SSRS questionnaires.
* Able to swallow and retain oral medication.
* 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 (45 days) plus 3 months (i.e. a total of 4.5 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.

Exclusion Criteria:

* Total serum PSA \>10.0 ng/mL at Visit 1 (screening).
* History or evidence of prostate cancer (e.g. positive biopsy or ultrasound, suspicious DRE and/or rising PSA). Subjects 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.

Excluded medication and therapies

* Current or prior use (within the periods given) of the following prohibited medications
* Any prior use of a 5α-reductase inhibitor (finasteride or dutasteride),
* Anti-cholinergics (e.g. oxybutynin, propantheline, tolerodine, solifenacin or darifenacin) within 1 month prior to visit 2 (baseline)
* An alpha-adrenoreceptor blocker (i.e. indoramin, prazosin, terazosin, tamsulosin, alfuzosin and doxazosin) within 1 month prior to visit 2 (baseline)
* Use of any drugs with anti-androgenic properties (e.g. spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, progestational agents) within the 6 months prior to visit 1 (screening).
* Use of any drugs noted for propensity to cause gynaecomastia, or which could affect prostate volume, within 6 months prior to Visit 1 (screening).
* Use of any investigational or marketed study drug within 30 days or 5 half-lives of the drug in question, (whichever is longer), preceding visit 2 (baseline).
* Current use (at the baseline visit or within the prior 1month) of:
* PDE-5 inhibitors for Erectile Dysfunction.
* 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.
* History of a known (immediate or delayed) hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to the study medication or excipients that, in the opinion of the Investigator or GSK, contraindicate their participation.
* Previous prostatic surgery (including TURP, balloon dilatation, thermotherapy and stent replacement) or other invasive or minimally invasive procedures to treat BPH.

Recent Medical Procedures

- 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

* Presence of structural abnormalities in the Lower Urinary Tract or sexual organs (e.g. urethral stricture, Peyronie's Disease etc) that may cause LUTS or sexual dysfunction.
* History of AUR.
* Post-void residual volume \>100 mL (suprapubic ultrasound) at Visit 1 (screening) or a recorded PVR above this level on any previous examination. Measurement should be available by the baseline visit and should have been made /arranged at the screening visit or within the previous 6 months.
* Any causes other than BPH, which may in the judgement of the investigator, result in urinary symptoms (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.
* 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.
* Prior history of malignancies (other than basal cell carcinoma or squamous cell carcinoma of the skin) within the past 5 years. Subjects with an earlier history of malignancy who have had no evidence of disease for at least the past 5 years are eligible.
* History of hepatic impairment or abnormal liver function tests at Visit 1 (screening) (defined as ALT, AST or alkaline phosphatase \>2 times the 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).
* 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 the 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.
* History or presence of any serious and/or unstable pre-existing psychiatric disorder or other conditions that in the opinion of the Investigator or GSK Medical Monitor, could interfere with subject's safety, obtaining informed consent, compliance to the study procedures, or confound the results of the study.