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(s) targeted: Prostatic Hyperplasia

Intervention: Dutasteride 0.5mg capsules (Drug); Dutasteride placebo capsules (Drug); Tamsulosin 0.2mg tablets (Drug); Disintegrating placebo tamsulosin tablet (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

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.

Official title: A Randomized, Double-blind, Parallel Group Study to Compare the Efficacy and Safety of Combination Treatment With Dutasteride (0.5mg) and Tamsulosin (0.2mg) With Tamsulosin (0.2mg) Monotherapy, Administered Once Daily for 2 Years, on the Improvement of Symptoms and Health Outcomes in Men With Moderate to Severe Benign Prostatic Hyperplasia

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Change From Baseline in the International Prostate Symptom Score (IPSS) at Year 2

Secondary outcome:

Percentage change from Baseline in Prostate Volume

Proportion of subjects with IPSS improvement of >=2 points and >=3 points from baseline and, separately, >=25% improvement from Baseline

Change from Baseline in maximum urinary flow rate (Qmax)

Proportion of subjects with Qmax improvement of >=3 milliliter per second (mL/sec) and, separately, >=30% improvement from baseline

Time to event/ proportion of subjects with acute urinary retention (AUR) or BPH related prostatic surgery

Time to event/proportion of subjects with AUR

Time to event/proportion of subjects undergoing BPH related prostatic surgery

Minimum age: 50 Years. Maximum age: N/A. Gender(s): Male.

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.

GSK Investigational Site, Beijing 100191, China

GSK Investigational Site, Beijing 100730, China

GSK Investigational Site, Beijing 100020, China

GSK Investigational Site, Chongqing 400037, China

GSK Investigational Site, Shanghai 200433, China

GSK Investigational Site, Shanghai 200025, China

GSK Investigational Site, Shanghai 200030, China

GSK Investigational Site, Shanghai 200032, China

GSK Investigational Site, Shanghai 200040, China

GSK Investigational Site, Fukuoka 810-0001, Japan

GSK Investigational Site, Fukuoka 811-0120, Japan

GSK Investigational Site, Hyogo 651-1145, Japan

GSK Investigational Site, Kanagawa 226-0025, Japan

GSK Investigational Site, Kanagawa 252-0143, Japan

GSK Investigational Site, Oita 874-0937, Japan

GSK Investigational Site, Osaka 530-0013, Japan

GSK Investigational Site, Saitama 343-0845, Japan

GSK Investigational Site, Tokyo 184-0005, Japan

GSK Investigational Site, Tokyo 150-0002, Japan

GSK Investigational Site, Yamanashi 400-0124, Japan

GSK Investigational Site, Busan 614-735, Korea, Republic of

GSK Investigational Site, Chonju 561-712, Korea, Republic of

GSK Investigational Site, Daegu 700-712, Korea, Republic of

GSK Investigational Site, Gwangju 501-757, Korea, Republic of

GSK Investigational Site, Incheon 405-760, Korea, Republic of

GSK Investigational Site, Seoul 110-744, Korea, Republic of

GSK Investigational Site, Seoul 135-710, Korea, Republic of

GSK Investigational Site, Seoul 135-720, Korea, Republic of

GSK Investigational Site, Seoul 156-707, Korea, Republic of

GSK Investigational Site, Seoul 138-736, Korea, Republic of

GSK Investigational Site, Seoul 150-713, Korea, Republic of

GSK Investigational Site, Seoul 136-705, Korea, Republic of

GSK Investigational Site, Chia-Yi 613, Taiwan

GSK Investigational Site, Hualien 970, Taiwan

GSK Investigational Site, Kaohsiung Hsien 83301, Taiwan

GSK Investigational Site, Kaohsiung, Taiwan

GSK Investigational Site, New Taipei City 23142, Taiwan

GSK Investigational Site, Tainan 704, Taiwan

GSK Investigational Site, Tainan 71004, Taiwan

GSK Investigational Site, Tau-Yuan 333, Taiwan

GSK Investigational Site, Xiame, Fujian, China

GSK Investigational Site, Guangzhou, Guangdong 510120, China

GSK Investigational Site, Wuhan, Hubei 430030, China

GSK Investigational Site, Suzhou, Jiangsu 215004, China

GSK Investigational Site, Shenyang, Liaoning, China

GSK Investigational Site, Hangzhou, Zhejiang 310003, China

Starting date: February 2014
Last updated: May 7, 2015