CONDUCT: 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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01294592
• Collaborator: (none)
• Enrollment: 742
• Locations: 80
• Arms: 2
• Actual Duration (Months): 33.8
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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the subjects return to site at one month, then every 13 weeks until two years of treatment is complete or they are withdrawn.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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hyperplasia	Drug: Dutasteride plus tamsulosin; Drug: tamsulosin	Phase 4

Detailed Description

This will be a European, multicentre, randomised, open-label, parallel group study. The aim of the study is to investigate whether Dutasteride plus Tamulson treatment with lifestyle advice is more effective than watchful waiting treatment plus lifestyle advice plus step-up therapy with tamsulosin for improvement of symptoms and Acte Urinary Retention (AUR) and BPH-related prostatic surgery, in older men (≥50 yrs), with moderate symptoms of BPH (IPSS 8-19), enlarged prostates (≥30cc) and Prostate Specific Antigen (PSA) ≥1.5ng/mL.

Data from all participating centres will be pooled prior to analysis. Investigative centres will be pooled a priori into clusters based on geographic location; these clusters may be used in analyses to adjust for site effects. Clusters will be defined once all investigative centres have been identified and randomisation has been completed.

Subjects will be screened for inclusion into the study and eligible subjects will be randomised by investigative centre. Subjects will be allocated to one of two treatment groups, according to a pre-determined randomisation schedule (in a 1:1 ratio):

• Dutasteride plus tamsulosin once daily plus lifestyle advice.

• Watchful waiting plus lifestyle advice. Escalation to tamsulosin 0.4 mg once daily at any visit from Week 4 if any IPSS measurement shows no improvement or worsening from baseline. At any study visit, if the IPSS is the same or greater than the baseline value for that subject, tamsulosin 0.4 mg once daily will be initiated. If tamsulosin is initiated, it will be continued for the remainder of the study unless the subject elects to withdraw from the study. Initiation of tamsulosin will be recorded in the electronic case report form (eCRF.) Subjects will self-administer study medication once daily for up to 104 weeks, (up to 100 weeks for those on tamsulosin). Subjects will return to the clinic at 4 weeks post-randomisation and then at 13-week intervals post-randomisation during the 2-year treatment period (i.e. at 4, 13, 26, 39, 52, 65, 78, 91 and 104 weeks) for the assessments listed as in Appendix 1 Time and Events Schedule.

Approximately 760, treatment naive men with symptomatic BPH will be randomised into the study in order to achieve at least 592 evaluable subjects. 380 into the Dutasteride plus tamsulosin with lifestyle advice arm and 380 into the watchful waiting plus lifestyle advice arm.

Treatment naïve is defined as a man that has recently been diagnoses with BPH whom has received no prescribed therapeutic treatment. For example, medicines such as 5 α-reductase inhibitors (5-ARIs) or invasive procedures such as transurethral resection of the prostate (TURP) prescribed to directly treat the BPH symptoms are considered therapeutic treatments. As per the entry criteria, phytotherapy is allowed unless it was performed less than two weeks prior to the screening visit.

The anticipated recruitment period will be approximately 6 months. The study will be conducted in approximately 8 countries within Europe.

Study Design

• Study Type: Interventional
• Actual Enrollment: 742 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparative Efficacy of DuodartTM Versus Watchful Waiting With Step-up Therapy to Tamsulosin in the Management of Treatment naïve Men With Symptomatic BPH
• Actual Study Start Date: Dec 22, 2010
• Actual Primary Completion Date: Oct 17, 2013
• Actual Study Completion Date: Oct 17, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dutasteride plus tamsulosin Dutasteride plus tamsulosin arm + lifestyle advice	Drug: Dutasteride plus tamsulosin; Take 1 capsule daily
Experimental: Watchful waiting with escalation to tamsulosin Watchful waiting with escalation to tamsulosin	Drug: tamsulosin; Take 1 capsule daily when escalation criteria met

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the Last Observation Carried Forward (LOCF) Approach [Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24]

   The IPSS questionnaire is a 7-item self-administered questionnaire designed to quantify the following urinary symptoms: Question 1 (Q1), incomplete emptying; Q2, frequency; Q3, intermittency; Q4, urgency; Q5, weak stream; Q6, straining; Q7, nocturia. It has an additional, independent eighth question to assess change in BPH-related health status (BHS) and quality of life. BHS scores range from 0 to 6, where 0 indicates "delighted" and 6 indicates "terrible." The 7 items in the IPSS questionnaire quantitatively measure the level of urinary symptoms reported as a total IPSS. The total IPSS (sum of the first 7 items) can range from 0 to 35: mild (0 to 7), moderate (8 to 19), or severe (20 to 35). Change from Baseline in IPSS total score was calculated as the Month 24 value minus the Baseline value. LOCF analysis involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study.

Secondary Outcome Measures

1. Number of Participants With Change From Baseline in the Indicated Improvement Categories in the IPSS at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach [Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24]

   Symptom improvement was assessed using IPSS categorical changes from Baseline. Change from Baseline categories were summarized by treatment group using five improvement levels: >=1 point through >=5 points. IPSS percent change from Baseline was summarized using seven improvement levels: >0 percent, >=10 percent, >=20 percent, >=25 percent, >=30 percent, >=40 percent, and >=50 percent. Change in IPSS from Baseline was analysed using the LOCF method and is summarized for the following categories: >=2 points, >=3 points, and percent change >=25. The 7 items in the IPSS questionnaire quantitatively measure the level of urinary symptoms reported as a total IPSS. The total IPSS (sum of the first 7 items) can range from 0 to 35: mild (0 to 7), moderate (8 to 19), or severe (20 to 35).

2. Change From Baseline in the BPH Impact Index (BII) Score at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach [Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24]

   The BII is a 4-item questionnaire covering physical discomfort, worry, bother, and impact on usual activities, with a minimum score of 0 (best) and a maximum score (worst) of 13 points. Individual missing questionnaire responses were imputed, as applicable. Change from Baseline in the BII score was summarized by treatment group using the LOCF approach at each scheduled post-Baseline assessment. LOCF analysis involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study. Estimates are based on the adjusted means from the general linear model: Change from Baseline =Treatment + Cluster + Baseline Value. Baseline is defined as the Visit 2 value if it exists; otherwise, it is the latest of all Screening values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

3. Change From Baseline in the BPH-related Health Status (BHS) Score at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach [Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24]

   Each participant was asked the following question "If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?". This response was rated from 0 ("delighted") to 6 ("terrible"). Change from Baseline in the BHS score was summarized by treatment group using the LOCF approach at each scheduled post-Baseline assessment. LOCF analysis involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study. Estimates are based on the adjusted means from the general linear model: Change from Baseline =Treatment + Cluster + Baseline Value. Baseline is defined as the Visit 2 value if it exists; otherwise, it is the latest of all Screening values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

4. Number of Events of Clinical Progression (CP) of BPH [Up to 2 years]

   The number of participants with the first occurrence of clinical progression (CP) of BPH occurring on or after the randomization date are summarized by treatment and year. Time is based on the date of the first-occurring CP event, and is relative to the randomization date. CP of BPH is a composite of five endpoints assessed through the end of the study, including: symptom deterioration by IPSS >=3 points from Baseline (Visit 2); acute urinary retention related to BPH; incontinence (overflow or urge) related to BPH; recurrent urinary tract infection (UTI) or urosepsis related to BPH; renal insufficiency related to BPH (a single >=50% rise from Baseline serum creatinine and a total value >=1.5 milligrams/deciliter). For components that required multiple episodes, the first of the multiple episodes was utilized in terms of timing.

5. Number of Participants With the Indicated First-occurring Component of Clinical Progression (CP) of BPH [Up to Month 24]

   CP of BPH is a composite of five endpoints assessed through the end of the study, including: symptom progression (symptom deterioration by IPSS >=3 points from Baseline [Visit 2]); acute urinary retention (AUR) related to BPH; incontinence (overflow or urge) related to BPH; recurrent urinary tract infection (UTI) or urosepsis related to BPH; renal insufficiency related to BPH (a single >=50% rise from Baseline serum creatinine and a total value >=1.5 milligrams/deciliter). The number of participants with CP of BPH, the number of participants with the indicated first-occurring component of CP of BPH, the number of participants with two simultaneously first-occurring components ("Tied for first component"), and the number of participants with multiple first-occurring components were summarized by treatment group.

6. Number of Participants Who Had Any BPH-related Surgery, Who Had the Indicated Type of Surgery, Who Had 2 BPH-related Surgeries, and Who Had >=3 BPH-related Surgeries [Up to Month 24]

   BPH-related surgery was summarized for events occurring on or after the date of randomization. The number of participants who had any BPH-related surgery, the indicated type of surgery, and multiple surgeries was summarized by treatment. Type of surgery data (cystoscopy, transurethral resection of the prostate [TURP], and prostatectomy) are presented in terms of the first-occurring BPH-related surgery after randomization. It was possible for a single participant to have multiple surgeries.

7. Number of Participants With the Indicated Responses to Question 1 of the Patient Perception of Study Treatment (PPST) Questionnaire at Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach [Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24]

   The PPST questionnaire consists of two questions (asked to determine how satisfied participants are with the treatment received) and was administered at Baseline and all post-Baseline visits. Question 1 was: "Overall, how satisfied are you with the treatment and its effect on your urinary problems?" There were seven possible responses, including: "very satisfied," "satisfied," "somewhat satisfied," neutral," "somewhat dissatisfied," "dissatisfied," and "very dissatisfied." Response categories were created by grouping together "very satisfied," "satisfied," and "somewhat satisfied" responses into the category of "Any Satisfaction (AS)," and separately grouping "neutral," "somewhat dissatisfied," "dissatisfied," and "very dissatisfied" responses into the category of "Neutral or Any Dissatisfaction (N/AD)." The LOCF method involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study.

8. Number of Participants With the Indicated Responses to Question 2 of the Patient Perception of Study Treatment (PPST) Questionnaire at Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach [Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24]

   The PPST questionnaire consists of two questions (asked to determine how satisfied participants are with the treatment received) and was administered at Baseline and all post-Baseline visits. Question 2 was: "Would you ask your doctor for the treatment you received in this study?" There were three possible responses, including: "Yes," "No," and "Not sure." Response categories included "Yes" and "No or Not Sure," created by grouping together "No" and "Not sure." The LOCF method involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study.

9. Exposure to Study Drug [Up to 2 years]

   Study drug exposure (days) = treatment stop date - treatment start date + 1. Participants in the Watchful Waiting Escalated=Yes subgroup could have been escalated to study drug at any time during the study. Therefore, it is possible that participants were exposed to tamsulosin for a shorter length of time than participants in the dutasteride plus tamsulosin group.

10. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Starting Post-randomization [Up to 2 years]

    A post-randomization adverse event is defined as an event with an onset on or after the randomization date or with a missing onset date. An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general non-serious AE/SAE module for a list of non-serious AEs (occurring at a frequency threshold of >=5%) and SAEs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Aigrefeuille Sur Maine		France	44140
2	GSK Investigational Site	Angers		France	49000
3	GSK Investigational Site	Angers		France	49933
4	GSK Investigational Site	Corsept		France	44560
5	GSK Investigational Site	La Montagne		France	44620
6	GSK Investigational Site	La Rochelle		France	17000
7	GSK Investigational Site	Laval		France	53000
8	GSK Investigational Site	Le Temple De Bretagne		France	44360
9	GSK Investigational Site	Murs Erigne		France	49610
10	GSK Investigational Site	Nantes		France	44300
11	GSK Investigational Site	Nieul sur Mer		France	17137
12	GSK Investigational Site	Sautron		France	44880
13	GSK Investigational Site	Thouars		France	79100
14	GSK Investigational Site	Tierce		France	49125
15	GSK Investigational Site	Vihiers		France	49310
16	GSK Investigational Site	Aichach	Bayern	Germany	86551
17	GSK Investigational Site	Nuernberg	Bayern	Germany	90441
18	GSK Investigational Site	Hagenow	Brandenburg	Germany	19230
19	GSK Investigational Site	Oranienburg	Brandenburg	Germany	16515
20	GSK Investigational Site	Strausberg	Brandenburg	Germany	15344
21	GSK Investigational Site	Marburg	Hessen	Germany	35039
22	GSK Investigational Site	Buchholz	Niedersachsen	Germany	21244
23	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45130
24	GSK Investigational Site	Hettstedt	Sachsen-Anhalt	Germany	06333
25	GSK Investigational Site	Leipzig	Sachsen	Germany	04109
26	GSK Investigational Site	Kiel	Schleswig-Holstein	Germany	24143
27	GSK Investigational Site	Berlin		Germany	10249
28	GSK Investigational Site	Eisleben		Germany	06295
29	GSK Investigational Site	Argos		Greece	21200
30	GSK Investigational Site	Athens		Greece	10552
31	GSK Investigational Site	Athens		Greece	115 22
32	GSK Investigational Site	Athens		Greece	11527
33	GSK Investigational Site	Athens		Greece	151 26
34	GSK Investigational Site	Larisa		Greece	41110
35	GSK Investigational Site	Patra		Greece	265 04
36	GSK Investigational Site	Rhodes		Greece	85100
37	GSK Investigational Site	Thessaloniki		Greece	546 42
38	GSK Investigational Site	Thessaloniki		Greece	564 29
39	GSK Investigational Site	Vasto (CH)	Abruzzo	Italy	66054
40	GSK Investigational Site	Avellino	Campania	Italy	83100
41	GSK Investigational Site	Napoli	Campania	Italy	80131
42	GSK Investigational Site	Roma	Lazio	Italy	00161
43	GSK Investigational Site	Milano	Lombardia	Italy	20132
44	GSK Investigational Site	San Fermo Della Battaglia (CO)	Lombardia	Italy	22020
45	GSK Investigational Site	Torino	Piemonte	Italy	10126
46	GSK Investigational Site	Foggia	Puglia	Italy	71100
47	GSK Investigational Site	Cagliari	Sardegna	Italy	09134
48	GSK Investigational Site	Pisa	Toscana	Italy	56124
49	GSK Investigational Site	Den Haag		Netherlands	2582 LJ
50	GSK Investigational Site	Doetinchem		Netherlands	7009 BL
51	GSK Investigational Site	Maarssen		Netherlands	3607 KN
52	GSK Investigational Site	Sneek		Netherlands	8601 ZK
53	GSK Investigational Site	Voerendaal		Netherlands	6367 ED
54	GSK Investigational Site	Wildervank		Netherlands	9648 BE
55	GSK Investigational Site	Winterswijk		Netherlands	7101 BN
56	GSK Investigational Site	Arad		Romania	310175
57	GSK Investigational Site	Bucharest		Romania
58	GSK Investigational Site	Alava		Spain	01004
59	GSK Investigational Site	Barcelona		Spain	8907
60	GSK Investigational Site	Cordoba		Spain	14004
61	GSK Investigational Site	Coslada		Spain	28822
62	GSK Investigational Site	Fuenlabrada (Madrid)		Spain	28942
63	GSK Investigational Site	Galdakano		Spain	48960
64	GSK Investigational Site	Getafe		Spain	28905
65	GSK Investigational Site	Malaga		Spain	29010
66	GSK Investigational Site	Marbella		Spain	29600
67	GSK Investigational Site	Mendaro, Guipuzcoa		Spain	20850
68	GSK Investigational Site	Murcia		Spain	30008
69	GSK Investigational Site	Pamplona		Spain	31008
70	GSK Investigational Site	San Sebastián		Spain	20014
71	GSK Investigational Site	Valencia		Spain	46010
72	GSK Investigational Site	Valladolid		Spain	47012
73	GSK Investigational Site	Chalfont St Giles	Buckinghamshire	United Kingdom	HP8 4QG
74	GSK Investigational Site	Sandbach	Cheshire	United Kingdom	CW11 1EQ
75	GSK Investigational Site	Bath		United Kingdom	BA1 3NG
76	GSK Investigational Site	Bristol		United Kingdom	BS2 8HW
77	GSK Investigational Site	Broadway, Fleetwood		United Kingdom	FY7 8GU
78	GSK Investigational Site	Chadderton, Oldham		United Kingdom	OL9 0LH
79	GSK Investigational Site	Glasgow		United Kingdom	G51 4TF
80	GSK Investigational Site	High Heaton, Newcastle Upon Tyne		United Kingdom	NE7 7DN

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• IPD for this study will be made available via the Clinical Study Data Request site.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01294592
• Other Study ID Numbers: 114615
• First Posted: Feb 11, 2011
• Last Update Posted: Aug 20, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Prostatic Hyperplasia; Hyperplasia; Tamsulosin; Dutasteride

Study Results

Participant Flow

Pre-assignment Detail	Treatment-naïve men with symptomatic benign prostatic hyperplasia (BPH) meeting eligibility criteria were enrolled and were randomized in a 1:1 ratio to receive dutasteride plus tamsulosin once daily plus lifestyle advice or watchful waiting plus lifestyle advice.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Period Title: Overall Study
STARTED	369	373
COMPLETED	292	300
NOT COMPLETED	77	73

Baseline Characteristics

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No	Total
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).	Total of all reporting groups
Overall Participants	369	373	742
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.3 (7.78)	66.2 (7.34)	66.2 (7.56)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	369 100%	373 100%	742 100%
Race/Ethnicity, Customized (Number) [Number]
White - White/Caucasian/European Heritage	357 96.7%	363 97.3%	720 97%
White - Arabic/North African Heritage	4 1.1%	2 0.5%	6 0.8%
African American/African Heritage	0 0%	2 0.5%	2 0.3%
Mixed Race	0 0%	1 0.3%	1 0.1%
Missing	8 2.2%	5 1.3%	13 1.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the Last Observation Carried Forward (LOCF) Approach
Description	The IPSS questionnaire is a 7-item self-administered questionnaire designed to quantify the following urinary symptoms: Question 1 (Q1), incomplete emptying; Q2, frequency; Q3, intermittency; Q4, urgency; Q5, weak stream; Q6, straining; Q7, nocturia. It has an additional, independent eighth question to assess change in BPH-related health status (BHS) and quality of life. BHS scores range from 0 to 6, where 0 indicates "delighted" and 6 indicates "terrible." The 7 items in the IPSS questionnaire quantitatively measure the level of urinary symptoms reported as a total IPSS. The total IPSS (sum of the first 7 items) can range from 0 to 35: mild (0 to 7), moderate (8 to 19), or severe (20 to 35). Change from Baseline in IPSS total score was calculated as the Month 24 value minus the Baseline value. LOCF analysis involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study.
Time Frame	Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not treatment was administered. Any participant who received a treatment randomization number was considered to have been randomized. Participants with data available at the specified time point or using LOCF (post-Baseline) were summarized.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	359	368
Month 1, n=358, 367	-3.2 (0.21)	-0.9 (0.20)
Month 3, n=359, 368	-4.5 (0.22)	-2.4 (0.22)
Month 6, n=359, 368	-4.6 (0.23)	-3.2 (0.22)
Month 9, n=359, 368	-5.1 (0.22)	-3.6 (0.22)
Month 12, n=359, 368	-5.2 (0.23)	-3.6 (0.23)
Month 15, n=359, 368	-5.2 (0.25)	-3.6 (0.24)
Month 18, n=359, 368	-5.1 (0.25)	-3.3 (0.25)
Month 21, n=359, 368	-5.5 (0.25)	-3.6 (0.24)
Month 24, n=359, 368	-5.4 (0.25)	-3.6 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 1
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -2.8 to -1.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 3
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -2.7 to -1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 6
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 9
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.2 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 12
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.2 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 15
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.3 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 18
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.4 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 21
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -2.5 to -1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Dutasteride Plus Tamsulosin, Watchful Waiting All: Escalated Yes and No
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Month 24
	Method	t-test, 2 sided
	Comments	Values are based on t-tests from the general linear model
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -2.5 to -1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	Estimates are based on the adjusted means from the general linear model: Change from Baseline = Treatment + Cluster + Baseline Value. The adjusted mean difference is based on dutasteride plus tamsulosin minus Watchful Waiting All.

2. Secondary Outcome

Title	Number of Participants With Change From Baseline in the Indicated Improvement Categories in the IPSS at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach
Description	Symptom improvement was assessed using IPSS categorical changes from Baseline. Change from Baseline categories were summarized by treatment group using five improvement levels: >=1 point through >=5 points. IPSS percent change from Baseline was summarized using seven improvement levels: >0 percent, >=10 percent, >=20 percent, >=25 percent, >=30 percent, >=40 percent, and >=50 percent. Change in IPSS from Baseline was analysed using the LOCF method and is summarized for the following categories: >=2 points, >=3 points, and percent change >=25. The 7 items in the IPSS questionnaire quantitatively measure the level of urinary symptoms reported as a total IPSS. The total IPSS (sum of the first 7 items) can range from 0 to 35: mild (0 to 7), moderate (8 to 19), or severe (20 to 35).
Time Frame	Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Participants with data available at the specified time point or using LOCF (post-Baseline) were summarized. LOCF analysis involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	359	368
Month 1, >=2 points, n=358, 367	225 61%	149 39.9%
Month 1, >=3 points, n=358, 367	182 49.3%	90 24.1%
Month 1, >=25 percent, n=358, 367	161 43.6%	76 20.4%
Month 3, >=2 points, n=359, 368	277 75.1%	221 59.2%
Month 3, >=3 points, n=359, 368	233 63.1%	172 46.1%
Month 3, >=25 percent, n= 359, 368	218 59.1%	150 40.2%
Month 6, >=2 points, n=359, 368	277 75.1%	250 67%
Month 6, >=3 points, n=359, 368	245 66.4%	208 55.8%
Month 6, >=25 percent, n=359, 368	229 62.1%	189 50.7%
Month 9, >=2 points, n=359, 368	286 77.5%	276 74%
Month 9, >=3 points, n=359, 368	257 69.6%	222 59.5%
Month 9, >=25 percent, n=359, 368	247 66.9%	207 55.5%
Month 12, >=2 points, n=359, 368	291 78.9%	273 73.2%
Month 12, >=3 points, n=359, 368	261 70.7%	229 61.4%
Month 12, >=25 percent, n= 359, 368	249 67.5%	214 57.4%
Month 15, >=2 points, n=359, 368	289 78.3%	275 73.7%
Month 15, >=3 points, n=359, 368	259 70.2%	243 65.1%
Month 15, >=25 percent, n=359, 368	245 66.4%	231 61.9%
Month 18, >=2 points, n=359, 368	288 78%	268 71.8%
Month 18, >=3 points, n=359, 368	262 71%	229 61.4%
Month 18, >=25 percent, 359, 368	245 66.4%	212 56.8%
Month 21, >=2 points, n=359, 368	292 79.1%	274 73.5%
Month 21, >=3 points, n=359, 368	267 72.4%	237 63.5%
Month 21, >=25 percent, n= 359, 368	253 68.6%	224 60.1%
Month 24, >=2 points, n=359, 368	295 79.9%	279 74.8%
Month 24, >=3points, n=359, 368	277 75.1%	234 62.7%
Month 24, >=25 percent, n= 359, 368	261 70.7%	221 59.2%

3. Secondary Outcome

Title	Change From Baseline in the BPH Impact Index (BII) Score at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach
Description	The BII is a 4-item questionnaire covering physical discomfort, worry, bother, and impact on usual activities, with a minimum score of 0 (best) and a maximum score (worst) of 13 points. Individual missing questionnaire responses were imputed, as applicable. Change from Baseline in the BII score was summarized by treatment group using the LOCF approach at each scheduled post-Baseline assessment. LOCF analysis involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study. Estimates are based on the adjusted means from the general linear model: Change from Baseline =Treatment + Cluster + Baseline Value. Baseline is defined as the Visit 2 value if it exists; otherwise, it is the latest of all Screening values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Participants with data available at the specified time point or using LOCF (post-Baseline) were summarized.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	359	368
Month 1, n=357, 366	-1.3 (0.11)	-0.4 (0.11)
Month 3, n=359, 368	-1.8 (0.11)	-1.0 (0.11)
Month 6, n=359, 368	-1.9 (0.11)	-1.3 (0.11)
Month 9, n=359, 368	-2.1 (0.11)	-1.5 (0.11)
Month 12, n=359, 368	-2.1 (0.12)	-1.5 (0.12)
Month 15, n=359, 368	-2.2 (0.12)	-1.5 (0.12)
Month 18, n=359, 368	-2.2 (0.12)	-1.4 (0.12)
Month 21, n=359, 368	-2.4 (0.12)	-1.6 (0.12)
Month 24, n=359, 368	-2.4 (0.12)	-1.6 (0.12)

4. Secondary Outcome

Title	Change From Baseline in the BPH-related Health Status (BHS) Score at Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach
Description	Each participant was asked the following question "If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?". This response was rated from 0 ("delighted") to 6 ("terrible"). Change from Baseline in the BHS score was summarized by treatment group using the LOCF approach at each scheduled post-Baseline assessment. LOCF analysis involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study. Estimates are based on the adjusted means from the general linear model: Change from Baseline =Treatment + Cluster + Baseline Value. Baseline is defined as the Visit 2 value if it exists; otherwise, it is the latest of all Screening values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Participants with data available at the specified time point or using LOCF (post-Baseline) were summarized.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	359	368
Month 1, n=358, 367	-0.8 (0.06)	-0.3 (0.05)
Month 3, n=359, 368	-1.1 (0.06)	-0.7 (0.06)
Month 6, n=359, 368	-1.2 (0.06)	-0.9 (0.06)
Month 9, n=359, 368	-1.3 (0.06)	-1.0 (0.06)
Month 12, n=359, 368	-1.3 (0.06)	-1.1 (0.06)
Month 15, n=359, 368	-1.4 (0.06)	-1.1 (0.06)
Month 18, n=359, 368	-1.4 (0.06)	-1.1 (0.06)
Month 21, n=359, 368	-1.5 (0.06)	-1.1 (0.06)
Month 24, n=359, 368	-1.5 (0.06)	-1.1 (0.06)

5. Secondary Outcome

Title	Number of Events of Clinical Progression (CP) of BPH
Description	The number of participants with the first occurrence of clinical progression (CP) of BPH occurring on or after the randomization date are summarized by treatment and year. Time is based on the date of the first-occurring CP event, and is relative to the randomization date. CP of BPH is a composite of five endpoints assessed through the end of the study, including: symptom deterioration by IPSS >=3 points from Baseline (Visit 2); acute urinary retention related to BPH; incontinence (overflow or urge) related to BPH; recurrent urinary tract infection (UTI) or urosepsis related to BPH; renal insufficiency related to BPH (a single >=50% rise from Baseline serum creatinine and a total value >=1.5 milligrams/deciliter). For components that required multiple episodes, the first of the multiple episodes was utilized in terms of timing.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants at risk for CP at the specified visit were analyzed.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	369	373
Year 1, n=369, 373	48	94
Year 2, n=276, 251	17	14

6. Secondary Outcome

Title	Number of Participants With the Indicated First-occurring Component of Clinical Progression (CP) of BPH
Description	CP of BPH is a composite of five endpoints assessed through the end of the study, including: symptom progression (symptom deterioration by IPSS >=3 points from Baseline [Visit 2]); acute urinary retention (AUR) related to BPH; incontinence (overflow or urge) related to BPH; recurrent urinary tract infection (UTI) or urosepsis related to BPH; renal insufficiency related to BPH (a single >=50% rise from Baseline serum creatinine and a total value >=1.5 milligrams/deciliter). The number of participants with CP of BPH, the number of participants with the indicated first-occurring component of CP of BPH, the number of participants with two simultaneously first-occurring components ("Tied for first component"), and the number of participants with multiple first-occurring components were summarized by treatment group.
Time Frame	Up to Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	369	373
Participants with CP of BPH, n=369, 373	65 17.6%	108 29%
BPH symptom progression, n=65, 108	59 16%	97 26%
BPH-related AUR, n=65, 108	2 0.5%	4 1.1%
BPH-related incontinence, n=65, 108	4 1.1%	3 0.8%
Recurrent BPH-related UTI, n=65, 108	0 0%	4 1.1%
BPH-related renal insufficiency, n=65, 108	0 0%	0 0%
Tied for first component, n=65, 108	0 0%	0 0%
Multiple components (2 components), n=65, 108	4 1.1%	9 2.4%
Multiple components (3 components), n=65, 108	0 0%	1 0.3%
Multiple components (>=4 components), n=65, 108	0 0%	1 0.3%

7. Secondary Outcome

Title	Number of Participants Who Had Any BPH-related Surgery, Who Had the Indicated Type of Surgery, Who Had 2 BPH-related Surgeries, and Who Had >=3 BPH-related Surgeries
Description	BPH-related surgery was summarized for events occurring on or after the date of randomization. The number of participants who had any BPH-related surgery, the indicated type of surgery, and multiple surgeries was summarized by treatment. Type of surgery data (cystoscopy, transurethral resection of the prostate [TURP], and prostatectomy) are presented in terms of the first-occurring BPH-related surgery after randomization. It was possible for a single participant to have multiple surgeries.
Time Frame	Up to Month 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	369	373
Participants with any BPH-related surgery	6 1.6%	3 0.8%
Participants with cystoscopy	5 1.4%	1 0.3%
Participants with TURP	2 0.5%	1 0.3%
Participants with prostatectomy	0 0%	1 0.3%
Participants with 2 surgeries	1 0.3%	0 0%
Participants with >=3 surgeries	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With the Indicated Responses to Question 1 of the Patient Perception of Study Treatment (PPST) Questionnaire at Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach
Description	The PPST questionnaire consists of two questions (asked to determine how satisfied participants are with the treatment received) and was administered at Baseline and all post-Baseline visits. Question 1 was: "Overall, how satisfied are you with the treatment and its effect on your urinary problems?" There were seven possible responses, including: "very satisfied," "satisfied," "somewhat satisfied," neutral," "somewhat dissatisfied," "dissatisfied," and "very dissatisfied." Response categories were created by grouping together "very satisfied," "satisfied," and "somewhat satisfied" responses into the category of "Any Satisfaction (AS)," and separately grouping "neutral," "somewhat dissatisfied," "dissatisfied," and "very dissatisfied" responses into the category of "Neutral or Any Dissatisfaction (N/AD)." The LOCF method involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study.
Time Frame	Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Participants with data available at the specified time point or using LOCF (post-Baseline) were summarized.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	359	364
Baseline, Any Satisfaction, n=315, 328	119 32.2%	122 32.7%
Baseline, Neutral/Any Dissatisfaction, n=315, 328	196 53.1%	206 55.2%
Month 1, Any Satisfaction, n=358, 349	272 73.7%	209 56%
Month 1, Neutral/Any Dissatisfaction, n=358, 349	86 23.3%	140 37.5%
Month 3, Any Satisfaction, n= 359, 359	300 81.3%	265 71%
Month 3, Neutral/Any Dissatisfaction, n=359, 359	59 16%	94 25.2%
Month 6, Any Satisfaction, n=359, 361	301 81.6%	285 76.4%
Month 6, Neutral /Any Dissatisfaction, n=359, 361	58 15.7%	76 20.4%
Month 9, Any Satisfaction, n=359, 361	304 82.4%	293 78.6%
Month 9, Neutral/Any Dissatisfaction, n= 359, 361	55 14.9%	68 18.2%
Month 12, Any Satisfaction, n=359, 363	311 84.3%	305 81.8%
Month 12, Neutral/Any Dissatisfaction, n=359, 363	48 13%	58 15.5%
Month 15, Any Satisfaction, n=359, 364	311 84.3%	299 80.2%
Month 15, Neutral/Any Dissatisfaction, n=359, 364	48 13%	65 17.4%
Month 18, Any Satisfaction, n=359, 364	305 82.7%	298 79.9%
Month 18, Neutral/Any Dissatisfaction, n=359, 364	54 14.6%	66 17.7%
Month 21, Any Satisfaction, n=359, 364	310 84%	300 80.4%
Month 21, Neutral/Any Dissatisfaction, n=359, 364	49 13.3%	64 17.2%
Month 24, Any Satisfaction, n=359, 364	312 84.6%	312 83.6%
Month 24, Neutral/Any Dissatisfaction, n=359, 364	47 12.7%	52 13.9%

9. Secondary Outcome

Title	Number of Participants With the Indicated Responses to Question 2 of the Patient Perception of Study Treatment (PPST) Questionnaire at Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24 Using the LOCF Approach
Description	The PPST questionnaire consists of two questions (asked to determine how satisfied participants are with the treatment received) and was administered at Baseline and all post-Baseline visits. Question 2 was: "Would you ask your doctor for the treatment you received in this study?" There were three possible responses, including: "Yes," "No," and "Not sure." Response categories included "Yes" and "No or Not Sure," created by grouping together "No" and "Not sure." The LOCF method involves bringing forward the last non-missing post-Baseline assessment for a participant with missing data and/or for a participant who discontinued from the study.
Time Frame	Baseline and Months 1, 3, 6, 9, 12, 15, 18, 21, and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Participants with data available at the specified time point or using LOCF (post-Baseline) were summarized.

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).
Measure Participants	359	364
Baseline, Yes, n=315, 328	109 29.5%	103 27.6%
Baseline, No or Not Sure, n=315, 328	206 55.8%	225 60.3%
Month 1, Yes, n=358, 347	224 60.7%	166 44.5%
Month 1, No or Not Sure, n=358, 347	134 36.3%	181 48.5%
Month 3, Yes, n=359, 357	232 62.9%	207 55.5%
Month 3, No or Not Sure, n=359, 357	127 34.4%	150 40.2%
Month 6, Yes, n=359, 360	232 62.9%	227 60.9%
Month 6, No or Not Sure, n=359, 360	127 34.4%	133 35.7%
Month 9, Yes, n=359, 361	238 64.5%	231 61.9%
Month 9, No or Not Sure, n=359, 361	121 32.8%	130 34.9%
Month 12, Yes, n=359, 363	240 65%	229 61.4%
Month 12, No or Not Sure, n=359, 363	119 32.2%	134 35.9%
Month 15, Yes, n=359, 364	246 66.7%	239 64.1%
Month 15, No or Not Sure, n=359, 364	113 30.6%	125 33.5%
Month 18, Yes, n=359, 364	235 63.7%	236 63.3%
Month 18, No or Not Sure, n=359, 364	124 33.6%	128 34.3%
Month 21, Yes, n=359, 364	249 67.5%	234 62.7%
Month 21, No or Not Sure, n=359, 364	110 29.8%	130 34.9%
Month 24, Yes, n=359, 364	243 65.9%	236 63.3%
Month 24, No or Not Sure, n=359, 364	116 31.4%	128 34.3%

10. Secondary Outcome

Title	Exposure to Study Drug
Description	Study drug exposure (days) = treatment stop date - treatment start date + 1. Participants in the Watchful Waiting Escalated=Yes subgroup could have been escalated to study drug at any time during the study. Therefore, it is possible that participants were exposed to tamsulosin for a shorter length of time than participants in the dutasteride plus tamsulosin group.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Treated Subjects Population: all participants starting protocol pharmacological treatment, either dutasteride plus tamsulosin or (escalated to) tamsulosin, as indicated by a nonmissing electronic Case Report Form treatment start date

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting Escalated=Yes
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any IPSS was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study.
Measure Participants	368	229
Mean (Standard Deviation) [days]	639.8 (215.49)	566.3 (195.13)

11. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Starting Post-randomization
Description	A post-randomization adverse event is defined as an event with an onset on or after the randomization date or with a missing onset date. An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general non-serious AE/SAE module for a list of non-serious AEs (occurring at a frequency threshold of >=5%) and SAEs.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Dutasteride Plus Tamsulosin	Watchful Waiting All: Escalated Yes and No	Watchful Waiting Escalated=Yes
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.	All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study. If participants did not receive tamsulosin, they were not classified as escalated (Watchful Waiting Escalated=No).	All participants were given lifestyle advice. If any IPSS was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study.
Measure Participants	369	373	229
Any AE	190 51.5%	119 31.9%	95 12.8%
Any SAE	38 10.3%	25 6.7%	19 2.6%

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious adverse events (AEs) starting post-randomization (including events with an onset on or after the randomization date or with a missing onset date) were collected (up to 2 years).
Adverse Event Reporting Description	SAEs and non-serious AEs are reported for members of the ITT Population.
Arm/Group Title	Dutasteride Plus Tamsulosin		Watchful Waiting All: Escalated Yes and No		Watchful Waiting Escalated=Yes
Arm/Group Description	Participants received a combination of dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg plus lifestyle advice for 24 months.		All participants were given lifestyle advice. If any International Prostate Symptom Score (IPSS) was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study.		All participants were given lifestyle advice. If any IPSS was the same or greater than the Baseline value at any study visit (post-randomization), participants received tamsulosin 0.4 mg once daily (Watchful Waiting Escalated=Yes). Tamsulosin was continued until the end of the study unless the participant elected to withdraw from the study.
All Cause Mortality
	Dutasteride Plus Tamsulosin		Watchful Waiting All: Escalated Yes and No		Watchful Waiting Escalated=Yes
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dutasteride Plus Tamsulosin		Watchful Waiting All: Escalated Yes and No		Watchful Waiting Escalated=Yes
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/369 (10.3%)		25/373 (6.7%)		19/229 (8.3%)
Blood and lymphatic system disorders
Anaemia	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Anaemia megaloblastic	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Lymphadenopathy	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Cardiac disorders
Atrial fibrillation	4/369 (1.1%)		2/373 (0.5%)		2/229 (0.9%)
Cardiac failure	1/369 (0.3%)		1/373 (0.3%)		1/229 (0.4%)
Acute myocardial infarction	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Aortic valve stenosis	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Atrioventricular block	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Cardiomyopathy	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Coronary artery disease	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Supraventricular tachycardia	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Tachycardia	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Tachyarrhythmia	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Heart valve incompetence	0/369 (0%)		1/373 (0.3%)		0/229 (0%)
Endocrine disorders
Goitre	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Eye disorders
Ulcerative keratitis	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Gastrointestinal disorders
Inguinal hernia	2/369 (0.5%)		1/373 (0.3%)		0/229 (0%)
Abdominal pain	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Anal fistula	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Gastritis	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Haemorrhoids	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Ileus	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Pancreatitis	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Pancreatitis acute	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Pancreatitis necrotising	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
General disorders
Chest pain	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Death	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Pyrexia	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Infections and infestations
Respiratory tract infection	1/369 (0.3%)		2/373 (0.5%)		2/229 (0.9%)
Cellulitis	2/369 (0.5%)		0/373 (0%)		0/229 (0%)
Diverticulitis	0/369 (0%)		2/373 (0.5%)		1/229 (0.4%)
Erysipelas	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Pilonidal cyst	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Pneumonia	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Urinary tract infection	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Infective exacerbation of chronic obstructive airways	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Infected cyst	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Abdominal sepsis	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Injury, poisoning and procedural complications
Ankle fracture	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Hip fracture	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Contusion	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Post procedural haemorrhage	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Wound	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Lower limb fracture	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Post procedural haematuria	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Craniocerebral injury	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Investigations
Transaminases increased	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Metabolism and nutrition disorders
Metabolic acidosis	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Musculoskeletal and connective tissue disorders
Arthritis	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Osteoarthritis	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Polymyalgia rheumatica	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/369 (0%)		2/373 (0.5%)		2/229 (0.9%)
Prostate cancer	0/369 (0%)		2/373 (0.5%)		1/229 (0.4%)
B-cell lymphoma	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Bladder neoplasm	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Bronchial carcinoma	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Metastases to bone	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Metastases to liver	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Hepatocellular carcinoma	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Myxoid liposarcoma	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Nervous system disorders
Presyncope	2/369 (0.5%)		0/373 (0%)		0/229 (0%)
Syncope	1/369 (0.3%)		1/373 (0.3%)		0/229 (0%)
Transient ischaemic attack	1/369 (0.3%)		1/373 (0.3%)		1/229 (0.4%)
Cerebellar infarction	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Cerebral infarction	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Dizziness	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Sciatica	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Renal and urinary disorders
Calculus bladder	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Renal failure acute	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Urinary retention	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Renal impairment	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Reproductive system and breast disorders
Prostatitis	1/369 (0.3%)		2/373 (0.5%)		1/229 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/369 (0.3%)		1/373 (0.3%)		1/229 (0.4%)
Dyspnoea	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Lung disorder	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Respiratory acidosis	0/369 (0%)		1/373 (0.3%)		1/229 (0.4%)
Respiratory failure	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Vascular disorders
Hypertension	1/369 (0.3%)		0/373 (0%)		0/229 (0%)
Other (Not Including Serious) Adverse Events
	Dutasteride Plus Tamsulosin		Watchful Waiting All: Escalated Yes and No		Watchful Waiting Escalated=Yes
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/369 (11.7%)		13/373 (3.5%)		12/229 (5.2%)
Reproductive system and breast disorders
Erectile dysfunction	31/369 (8.4%)		4/373 (1.1%)		3/229 (1.3%)
Retrograde ejaculation	19/369 (5.1%)		10/373 (2.7%)		10/229 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.