Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparative Efficacy of DuodartTM Versus Watchful Waiting With Step-up Therapy to Tamsulosin in the Management of Treatment naïve Men With Symptomatic BPH
Brief 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the subjects return to site at one month, then every 13 weeks until two years of treatment is complete or they are withdrawn.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.


Options:
A: * 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.
B: Inclusion Criteria:

* new patients with uncomplicated LUTS (I-PSS score 0-35)
* aged 40 years and over
* referred for the first time by their family doctor (general practitioner) to one of a participating urological outpatient departments

Exclusion Criteria:

* lower urinary tract symptoms due to any urological malignancy
* previous prostatic surgery within the last 10 years or pelvic radiotherapy
* complications of urinary obstruction (acute or chronic urinary retention - post micturition volumes over 300ml, bladder stones, renal failure, recurrent urinary tract infection or haematuria)
* uncontrolled diabetes, dementia and end stage cardiac or respiratory failure
* inability to speak or understand the English language
* severe symptoms where drug therapy or surgical management is indicated or requested by the patient
* medical therapy for lower urinary tract symptoms in the previous 3 months, including alpha-blockers, 5-alpha reductase inhibitors (finasteride) or anti-cholinergics.
C: Inclusion Criteria:

* Male
* Community-dwelling
* Veteran
* Self-reported urgency
* Self-reported frequent urination
* Mean of \> 8 voids per 24-hour day on bladder diary
* Able to come to clinic

Exclusion Criteria:

* Urologic surgery in the past 6 months
* Nonambulatory (unless has independent transfer skills)
* Flow rate \< 5mL at baseline and \< 10mL/sec after run-in (on simple uroflowmetry)
* Post-void residual urine volume \> 250mL at baseline and \> 150mL after run-in (on bladder ultrasound)
* Continual leakage
* Urinary tract infection (growth of \> 100,000 colonies per ml of a urinary pathogen on urine culture). May be reconsidered after treatment and negative culture.
* Fecal impaction
* Poorly controlled diabetes (glycosylated hemoglobin \>9 within last 3 months)
* Hematuria on microscopic examination in the absence of infection
* Any unstable medical condition (particularly: decompensated congestive heart failure, malignant arrhythmias, unstable angina)

  -- Impaired mental status (\< 24 on Folstein's Mini-Mental State Exam)
* Narrow angle glaucoma
* Gastric retention (by medical history)
* Hypersensitivity to tamsulosin or oxybutynin
* Current use of anticholinergic agents for detrusor instability. May be reconsidered after 2-week wash-out.
* If on diuretic, dose has not been stable for at least three months
* Sleep apnea, unless surgically corrected
D: Inclusion Criteria:

1. Nocturia ≥2 episodes / night average on the screening diary;
2. Willingness and appropriateness to receive an α- blocker;
3. Willingness to keep a bladder and sleep diary;
4. Willingness to wear a wrist actigraph; and
5. Willingness to make study visits

Exclusion Criteria:

1. Evidence of overt bladder outlet obstruction: peak uroflow \<4 mL/sec on a void of ≥125 mL, or a PVR of ≥ 300 mL;
2. Use of clean intermittent self-catheterization at home or having been instructed by a provider to do so within the last 12 months;
3. Genitourinary cancer, including active prostate cancer with ongoing surgical or radiation treatment, or the need of treatment, or bladder cancer, or persistent unexplained hematuria;
4. Obstructive sleep apnea with CPAP use, provider diagnosis with symptoms, or strong suspicion of diagnosis during screening;
5. Having Parkinson's disease with an uncontrolled tremor (invalidates wrist actigraphy);
6. Poorly controlled congestive heart failure as evidenced on physical examination;
7. Poorly controlled diabetes mellitus with either hemoglobin A1c of ≥ 7.5 or a random glucose ≥ 200 within last 3 months; or
8. Unstable health conditions expected to result in death or hospitalization within 3 months, as assessed by PI or Site PI;
9. Previously receiving intensive bladder training;
10. Allergic to Tamsulosin;
11. Previous spinal cord injury;
12. Currently on dialysis or in consideration for dialysis due to end stage renal disease;
13. More than 2 urinary tract infections within the last 12 months;
14. Not able to transfer independently from a wheelchair to the toilet;
15. Unstable dose of diuretic within the past 3 months;
16. Has an artificial urinary sphincter;
17. Impaired mental status;
18. TURP or other urologic surgery within the last 6 months.

Answer: A