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Benign Prostatic Hyperplasia Trial With Dutasteride And Tamsulosin Combination Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00090103
Recruitment Status : Completed
First Posted : August 26, 2004
Results First Posted : March 16, 2010
Last Update Posted : February 28, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Prostatic Hyperplasia
Interventions Drug: dutasteride 0.5mg once daily for 4 years
Drug: tamsulosin 0.4mg once daily for 4 years
Enrollment 4844
Recruitment Details  
Pre-assignment Details In a 4-week, single-blind placebo run-in period, all participants (par.) took two capsules consisting of one dutasteride-matched placebo capsule and one tamsulosin-matched placebo capsule once daily for 4 weeks. A safety follow-up was performed for all participants 16 weeks after the last dose of study drug.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Period Title: Four-Year Double-Blind Treatment Period
Started 1610 1623 1611
Completed 1113 1093 989
Not Completed 497 530 622
Reason Not Completed
Adverse Event             211             185             210
Withdrawal by Subject             114             160             148
Lost to Follow-up             53             48             58
Protocol Violation             29             29             34
Lack of Efficacy             53             71             104
Participant Relocated             7             2             8
Site Closed/Sponsor Termination             7             7             4
Non-compliant/Medication Interruption             6             4             7
Prostate Surgery/TURP/Alt. Therapy             3             7             19
Participant Decision/Withdrawn             2             0             4
Acute Urinary Retention (AUR)             2             3             6
Prohibited Medication             2             2             8
Investigator Departure             2             0             0
Alcohol Dependent             1             0             0
Screen Failure             1             0             0
No Improvement             1             0             0
BPH/BPH symptoms worse/urinary incont.             1             0             5
Financial Problems             1             0             0
Loss of Libido             1             0             0
Angina Pectoris             0             2             0
Loss of Contact             0             1             0
Neoplasm of Bladder/Prostate             0             1             1
Cardiologist/Neurologist Decision             0             2             0
Renal Insufficiency             0             1             0
Back Pain             0             1             0
Scheduling Issues             0             1             0
Any Appreciable Improvement             0             1             0
Investigator Decision             0             1             3
Enrollment Error             0             0             2
Urinary Tract Infection (UTI)             0             0             1
Prostate Specific Antigen Rising             0             1             0
Period Title: 16-Week Safety Follow-up Period
Started 1598 [1] 1615 [1] 1600 [1]
Completed 1224 1205 1143
Not Completed 374 410 457
Reason Not Completed
Adverse Event             34             39             44
Withdrawal by Subject             185             212             229
Lost to Follow-up             101             97             111
Protocol Violation             18             18             17
Site Closed/Sponsor Termination             8             5             4
Non-compliant/Medication Interruption             8             6             4
Loss of Contact             4             0             2
Disease Progression/Treatment Failure             3             1             1
Participant relocated             2             3             1
Participant Decision/Withdrawn             2             1             2
Prohibited Medication             2             3             5
Alcohol Dependent             1             0             1
Prostate surgery/TURP/Alt. therapy             1             5             13
Loss of Libido             1             0             0
Enrollment Error             1             0             2
Neoplasm of Bladder/Prostate Cancer             1             3             6
Death             1             0             1
Gyneomastia             1             0             0
Acute Urinary Retention (AUR)             0             5             4
BPH/BPH symptoms worse/urinary incont.             0             2             3
Angina Pectoris             0             1             0
Back Pain             0             1             0
Scheduling Issues             0             2             4
Investigator/Sponsor Decision             0             2             3
Depression             0             1             0
Diabetes Uncontrolled             0             1             0
Jailed             0             1             0
Other             0             1             0
[1]
Some par. didn't enter the Follow-up phase or dropped out before completing the treatment phase.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg Total
Hide Arm/Group Description Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks Total of all reporting groups
Overall Number of Baseline Participants 1610 1623 1611 4844
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1610 participants 1623 participants 1611 participants 4844 participants
66.0  (7.05) 66.0  (6.99) 66.2  (7.00) 66.1  (7.01)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1610 participants 1623 participants 1611 participants 4844 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
1610
 100.0%
1623
 100.0%
1611
 100.0%
4844
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1610 participants 1623 participants 1611 participants 4844 participants
White 1421 1433 1405 4259
Black 22 17 24 63
Asian 107 106 112 325
American Hispanic 44 48 55 147
Unknown 16 19 15 50
1.Primary Outcome
Title Number of Events of Acute Urinary Retention (AUR) or Benign Prostatic Hyperplasia (BPH)-Related Prostatic Surgery at the Indicated Time Periods.
Hide Description A participant was considered to have AUR when he was unable to urinate and required bladder catheterization. BPH is also known as an enlarged prostate. When symptoms of BPH become bothersome, surgery may be required. When events of AUR and BPH-related surgery were participant-reported or identified, they were recorded in the participants' clinic record.
Time Frame Years 1, 2, 3, and 4
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to the double-blind treatment period. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1610 1623 1611
Measure Type: Number
Unit of Measure: events
Year 1, n=1610, 1623, 1611 29 27 40
Year 2, n=1457, 1484, 1464 14 22 62
Year 3, n=1347, 1365, 1307 15 16 44
Year 4, n=1274, 1277, 1176 9 19 45
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments Log-rank test with stratification by cluster.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk Estimate
Estimated Value 0.80
Confidence Interval 95%
0.58 to 1.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Tamsulosin 0.4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Log-rank test with stratification by cluster.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk Estimate
Estimated Value 0.34
Confidence Interval 95%
0.26 to 0.45
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With AUR or BPH-related Surgery
Hide Description A participant was considered to have AUR when he was unable to urinate and required bladder catheterization. BPH is also known as an enlarged prostate. When symptoms of BPH become bothersome, surgery may be required. When events of AUR and BPH-related surgery were participant reported or identified, they were recorded in the participants' clinic record.
Time Frame Baseline (Day 1) through Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1610 1623 1611
Measure Type: Number
Unit of Measure: participants
AUR 35 44 109
BPH-related surgery 32 40 82
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments Log rank test with stratification by cluster.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Tamsulosin 0.4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Log rank test with stratification by cluster.
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Number of Events of First BPH Clinical Progression at Years 1, 2, 3 and 4
Hide Description The time when the first symptom/event of BPH clinical progression has occurred (i.e. AUR, incontinence) was measured. Summaries are based on the first occuring event after treatment start. The time period is from treatment start to each participant's last treatment visit. The Year 4 events include all those that occur during the fourth year and beyond.
Time Frame Years 1, 2, 3, and 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1610 1623 1611
Measure Type: Number
Unit of Measure: events
Year 1, n=1610, 1623, 1611 126 184 171
Year 2, n= 1264, 1240, 1262 31 54 78
Year 3, n=1135, 1082, 1048 30 29 67
Year 4, n= 1047, 959, 880 16 22 31
4.Secondary Outcome
Title The Number of Participants With Each of the Five Components of BPH Clinical Progression
Hide Description The five components measured were symptom deterioration, BPH-related AUR, BPH-related incontinence, recurrent BPH-related Urinary Tract Infection (UTI), and BPH-related renal insufficiency.
Time Frame Baseline (Day 1) to Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1610 1623 1611
Measure Type: Number
Unit of Measure: participants
Symptom deterioration 132 203 221
BPH-related AUR 22 31 64
BPH-related incontinence 46 49 56
Recurrent BPH-related UTI 2 5 3
BPH-related renal insufficiency 1 2 5
5.Secondary Outcome
Title Number of Events of Symptom Deterioration at the Indicated Time Periods
Hide Description The number of participants (par.) with symptom deterioration of International Prostate Symptom Score (IPSS) ≥4 points on two consecutive visits post-baseline are presented. Data are based on the first occurrence of an event after treatment start. The year-4 events include all that occured during the 4th year and beyond. The IPSS is a 7-item questionnaire measuring the level of urinary symptoms reported as the total score. Each question has a 6-point response scale (0=none/not at all to 5=almost always), with a total score ranging from 0-35: mild (0-7), moderate (8-19), or severe (20-35).
Time Frame Years 1, 2, 3, and 4 (from treatment start until each participant's last treatment-phase visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to the double-blind treatment period. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1610 1623 1611
Measure Type: Number
Unit of Measure: events
Year 1, n=1610, 1623, 1611 91 138 119
Year 2, n=1286, 1278, 1296 23 38 49
Year 3, n=1158, 1132, 1088 14 23 42
Year 4, n=1083, 1001, 926 11 13 19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments Log-rank test with stratification by cluster.
Method of Estimation Estimation Parameter Relative Risk Estimate
Estimated Value 0.65
Confidence Interval 95%
0.52 to 0.80
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Tamsulosin 0.4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk Estimate
Estimated Value 0.59
Confidence Interval 95%
0.48 to 0.72
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With an Event of Post-baseline BPH-related Macroscopic Hematuria
Hide Description A participant was considered to have macroscopic hematuria when there was presence of blood in the urine. The event of macroscopic hematuria was either participant-reported or identified by the investigator during a clinic visit. Overall Crude Rate is the number of participants from the total number analyzed that experience experienced an incident of post-baseline BPH or Non-BPH related macroscopic hematuria. Participants may appear in both categories.
Time Frame Baseline (Day 1) through Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1610 1623 1611
Measure Type: Number
Unit of Measure: participants
Overall crude rate 53 70 81
Non-BPH-related Crude Rate 15 28 25
BPH-Related Crude Rate 40 45 56
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method Log Rank
Comments Mantel-Haenszel test with stratification by cluster.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Tamsulosin 0.4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Log Rank
Comments Mantel-Hanenszel test with stratification by cluster.
7.Secondary Outcome
Title Number of Participants With an Event of Post-baseline BPH-related Hematospermia
Hide Description A participant was considered to have hematospermia when there was presence of blood in the semen. Hematospermia can occur from prostatitis (prostate infection), from cancer, or after a prostate biopsy. The event of hematospermia was either participant-reported or identified by the investigator during a clinic visit. Overall Crude Rate is the number of participants from the total number analyzed that experience experienced an incident of post-baseline BPH or Non-BPH related hematospermia. Participants may appear in both categories.
Time Frame Baseline (Day 1) through Year 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1610 1623 1611
Measure Type: Number
Unit of Measure: participants
Overall Crude Rate 18 19 20
Non-BPH-related Crude Rate 2 3 9
BPH-related Crude Rate 17 17 11
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Dutasteride 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments [Not Specified]
Method Log Rank
Comments Mantel-Haenszel test with stratification by cluster.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg, Tamsulosin 0.4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method Log Rank
Comments Mantel-Haenszel test with stratification by cluster.
8.Secondary Outcome
Title Adjusted Mean Change From Baseline in International Prostate Symptom Score (IPSS) at Months 12, 24, 36, and 48
Hide Description The IPSS is a 7-item questionnaire that measures urinary symptoms. It measures the level of urinary symptoms (including incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) reported as the total IPSS score. Each of the 7 questions has a 6-point response scale (0=none/not at all to 5=almost always) with a total score that can range from 0-35: mild (0-7), moderate (8-19), or severe (20-35). Estimates are based on adjusted (least squares) means from the general linear model: change from baseline IPSS = Treatment + Cluster + Baseline IPSS.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1575 1592 1582
Least Squares Mean (Standard Error)
Unit of Measure: points on a scale
Month 12 -5.6  (0.15) -4.2  (0.15) -4.5  (0.15)
Month 24 -6.2  (0.15) -4.9  (0.15) -4.3  (0.15)
Month 36 -6.3  (0.16) -5.2  (0.16) -4.0  (0.16)
Month 48 -6.3  (0.16) -5.3  (0.16) -3.8  (0.16)
9.Secondary Outcome
Title Adjusted Mean Change From Baseline in Urinary Flow Rate (Qmax) at Months 12, 24, 36, and 48
Hide Description Peak maximum urinary flow (Qmax) of urinary flow using a Medtronic (formerly Dantec) Uroflow Meter (Urodyn 1000 or Duet models) with a Thompson filter was measured. Estimates are based on adjusted (least squares) means from the general linear model: Change from baseline Qmax = treatment + cluster + baseline Qmax.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Also, assessments with voided volumes <125 ml were not included in the analysis.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1495 1505 1523
Least Squares Mean (Standard Error)
Unit of Measure: milliliters (mL)/second (sec)
Month 12, n=1477, 1482, 1510 2.0  (0.12) 1.5  (0.12) 0.9  (0.12)
Month 24, n= 1492, 1501, 1519 2.4  (0.12) 1.9  (0.12) 0.9  (0.12)
Month 36, n= 1495, 1504, 1521 2.6  (0.12) 1.9  (0.12) 0.6  (0.12)
Month 48, n= 1495, 1505, 1523 2.4  (0.13) 2.0  (0.13) 0.7  (0.13)
10.Secondary Outcome
Title Adjusted Mean Percent Change From Baseline in Prostate Volume at Months 12, 24, 36, and 48
Hide Description Prostate volume measurements were conducted annually using Transurethral ultrasound (TRUS). The anteroposterior, cephalocaudal, and transverse diameters of the prostate obtained by TRUS calculate the total prostate volume centimeters (cc). Percent change from baseline = [(post-baseline - baseline)/baseline value] x 100. Estimates were based on the adjusted (least squares) means from the general linear model: log(post-baseline/baseline value) + treatment + cluster + log(baseline value) and are reported as percent change from baseline.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Also, prostate measurements were either not performed or missing for some participants at various timepoints.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1430 1455 1468
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Month 12, n=1411, 1442, 1451 -24.1  (0.60) -25.2  (0.59) -1.5  (0.77)
Month 24, n= 1427, 1451, 1465 -26.9  (0.62) -28.0  (0.61) 0.0  (0.84)
Month 36, n= 1430, 1455, 1468 -27.6  (0.68) -28.8  (0.66) 1.6  (0.94)
Month 48, n= 1430, 1455, 1468 -27.3  (0.66) -28.0  (0.65) 4.6  (0.94)
11.Secondary Outcome
Title Adjusted Mean Change From Baseline in Transition Zone (Portion of the Prostate That Surrounds the Proximal Urethra) Volume at Months 12, 24, 36, and 48
Hide Description Prostate volume (PV) measurements were conducted annually using Transurethral ultrasound (TRUS). The anteroposterior, cephalocaudal, and transverse diameters of the prostate obtained by TRUS calculate the total PV in centimeters (cc). Results are for the transition zone measurements of the prostate in a small subset of participants. Percent change from baseline (BL) = [(post-BL - BL)/BL value] x 100. Estimates are based on the adjusted (least squares) means for the general linear model: log(post-BL/BL value) = treatment + cluster + log(BL value) and are reported as percent change from BL.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Transition zone measurements were only done on a subset of participants at sites with experience in measuring the transition zone of the prostate. Also, transition zone measurements were either not performed or missing for some participants at various timepoints.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 155 164 163
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Month 12, n= 150, 159, 160 -17.2  (3.29) -15.6  (3.39) 5.6  (4.09)
Month 24, n= 153, 164, 160 -23.4  (5.63) -22.8  (5.86) 8.7  (8.22)
Month 36, n= 155, 164, 162 -20.9  (3.97) -26.7  (3.90) 14.7  (5.89)
Month 48, n= 155, 164, 163 -17.9  (4.45) -26.5  (4.21) 18.2  (6.54)
12.Secondary Outcome
Title Number of Unscheduled Visits to GP/Urologist Regarding AUR Symptoms Since the Last Study Visit
Hide Description At each scheduled 13-week clinic visit post-randomization, the investigator was to record details of any health care utilization associated with an episode of AUR. Responses to the following question were recorded: "Has the participant needed to make any unscheduled visits to his general practitioner (GP)/Urologist regarding AUR symptoms since the last study visit?" If the answer to the question was “yes,” the number of visits was recorded.
Time Frame Every 3 months from Month 3 to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1550 1581 1565
Measure Type: Number
Unit of Measure: visits
Month 3, n=1550, 1581, 1565 8 6 7
Month 6, n=1479, 1517, 1514 2 4 3
Month 9, n=1439, 1465, 1477 4 3 8
Month 12, n=1400, 1431, 1434 3 3 9
Month 15, n=1343, 1386, 1380 3 6 6
Month 18, n=1318, 1350, 1328 3 4 10
Month 21, n=1281, 1326, 1287 3 3 9
Month 24, n=1263, 1293, 1244 2 2 7
Month 27, n=1233, 1262, 1206 1 6 7
Month 30, n=1222, 1221, 1166 3 2 8
Month 33, n=1202, 1199, 1128 3 4 5
Month 36, n=1187, 1174, 1095 2 1 5
Month 39, n=1160, 1144, 1055 2 2 5
Month 42, n=1149, 1126, 1035 3 2 8
Month 45, n=1129, 1110, 1009 1 2 4
Month 48, n=1113, 1093, 990 1 2 2
13.Secondary Outcome
Title Number of "Yes" Responses to the Question: "Would the Participant Have Paid a Visit to His GP/Urologist Regarding AUR Symptoms if the Study Visit Had Not Been Planned"?.
Hide Description At each scheduled 13-week clinic visit post-randomization, the investigator was to record details of any health care utilization associated with an episode of AUR. Responses to the following question were recorded: "Would the participant have paid a visit to his GP/Urologist regarding AUR symptoms if this study visit had not been planned?". If the answer to the question was “yes,” the number of Yes responses was recorded.
Time Frame Every 3 months from Month 3 to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1550 1581 1564
Measure Type: Number
Unit of Measure: yes responses
Month 3, n=1550, 1581, 1564 31 32 29
Month 6, n=1479, 1516, 1513 21 26 26
Month 9, n=1439, 1465, 1477 18 14 18
Month 12, n=1400, 1431, 1434 8 13 9
Month 15, n=1343, 1386, 1380 9 15 12
Month 18, n=1318, 1350, 1328 17 13 19
Month 21, n=1281, 1326, 1287 10 15 17
Month 24, n=1263, 1293, 1244 5 9 8
Month 27, n=1233, 1262, 1206 9 11 8
Month 30, n=1222, 1221, 1166 7 9 9
Month 33, n=1202, 1199, 1128 9 10 11
Month 36, n=1187, 1174, 1095 5 4 5
Month 39, n=1160, 1144, 1055 7 9 6
Month 42, n=1149, 1126, 1035 6 8 8
Month 45, n=1129, 1110, 1009 7 8 5
Month 48, n=1113, 1093, 990 2 9 5
14.Secondary Outcome
Title Number of Visits to GP/Urologist Regarding BPH-related Surgery Since the Last Study Visit
Hide Description At each scheduled 13-week clinic visit post-randomization, the investigator was to record details of any health care utilization associated with BPH-related surgery. Responses to the following question were recorded: "Has the participant needed to visit his general practitioner (GP)/Urologist regarding BPH-related surgery since the last study visit?". If the answer to the question was “yes,” the number of visits was recorded.
Time Frame Every 3 months from Month 3 to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1550 1581 1564
Measure Type: Number
Unit of Measure: visits
Month 3, n=1550, 1581, 1564 0 3 3
Month 6, n=1479, 1517, 1514 2 1 2
Month 9, n=1439, 1465, 1477 2 2 3
Month 12, n=1400, 1431, 1434 1 2 7
Month 15, n=1343, 1386, 1380 2 5 7
Month 18, n=1318, 1350, 1328 4 0 4
Month 21, n=1281, 1326, 1287 1 0 3
Month 24, n=1263, 1293, 1244 2 0 3
Month 27, n=1233, 1262, 1206 3 3 4
Month 30, n=1222, 1221, 1165 0 1 1
Month 33, n=1202, 1199, 1128 0 1 5
Month 36, n=1187, 1174, 1095 2 2 1
Month 39, n=1160, 1144, 1055 1 3 2
Month 42, n=1149, 1126, 1035 1 2 5
Month 45, n=1129, 1110, 1009 0 3 2
Month 48, n=1113, 1093, 990 0 2 1
15.Secondary Outcome
Title Number of "Yes" Responses to the Question: "Would the Participant Have Paid a Visit to His GP/Urologist Regarding BPH-related Surgery Since the Last Study Visit?"
Hide Description At each scheduled 13-week clinic visit post-randomization, the investigator was to record details of any health care utilization associated with BPH-related surgery. Responses to the following question were recorded: "Would the participant have paid a visit to his general practitioner (GP)/Urologist regarding BPH-related surgery since the last study visit?". If the answer to the question was “yes,” the number of Yes responses was recorded.
Time Frame Every 3 months from Month 3 to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As study progressed, participants dropped out of study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1550 1581 1564
Measure Type: Number
Unit of Measure: yes responses
Month 3, n=1550, 1581, 1564 16 34 28
Month 6, n=1479, 1516, 1513 20 23 16
Month 9, n=1438, 1465, 1477 12 10 17
Month 12, n=1400, 1431, 1434 5 10 6
Month 15, n=1343, 1386, 1380 9 9 9
Month 18, n=1318, 1350, 1328 13 12 10
Month 21, n=1281, 1326, 1287 10 9 8
Month 24, n=1263, 1293, 1244 4 7 3
Month 27, n=1233, 1262, 1206 9 9 5
Month 30, n=1222, 1221, 1166 7 9 4
Month 33, n=1202, 1199, 1128 5 7 8
Month 36, n=1187, 1174, 1095 3 5 2
Month 39, n=1160, 1144, 1055 7 8 5
Month 42, n=1149, 1126, 1034 9 8 2
Month 45, n=1129, 1110, 1009 6 8 5
Month 48, n=1113, 1093, 990 1 3 1
16.Secondary Outcome
Title Number of Unplanned Visits to GP/Urologist That Would Have Taken Place if a Scheduled Study Visit Had Not Been Planned (Including Visits Resulting From UTI, UI, Macroscopic Haematuria, Etc.)
Hide Description At each scheduled 13-week clinic visit post-randomization, the investigator was to record details of any health care utilization associated with unplanned visits to GP/Urologist. Responses to the following question were recorded: "Has the participant had any unplanned GP/Urologist (outpatient) visits that would have taken place if a scheduled study visit had not been planned (this can include visits resulting from UTI, UI macroscopic haematuria, etc?". If the answer to the question was “yes,” the number of visits was recorded.
Time Frame Every 3 months from Month 3 to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1550 1581 1564
Measure Type: Number
Unit of Measure: visits
Month 3, n=1550, 1581, 1564 23 25 26
Month 6, n=1479, 1517, 1514 23 34 22
Month 9, n=1439, 1465, 1477 16 35 22
Month 12, n=1400, 1431, 1434 30 29 34
Month 15, n=1343, 1386, 1380 24 22 27
Month 18, n=1318, 1350, 1328 21 25 26
Month 21, n=1281, 1326, 1287 18 21 14
Month 24, n=1263, 1293, 1244 10 19 21
Month 27, n=1233, 1262, 1206 15 11 14
Month 30, n=1222, 1221, 1166 7 8 10
Month 33, n=1202, 1199, 1128 4 5 10
Month 36, n=1187, 1174, 1095 5 4 7
Month 39, n=1160, 1144, 1055 6 13 19
Month 42, n=1149, 1126, 1035 4 8 12
Month 45, n=1129, 1110, 1009 3 5 6
Month 48, n=1113, 1093, 990 1 6 5
17.Secondary Outcome
Title Number of Unscheduled Visits to GP/Urologist (Outpatient) Planned, Not Relating to the Study (Including Visits Resulting From UTI, UI, Macroscopic Haematuria, Etc.)
Hide Description At each scheduled 13-week clinic visit post-randomization, the investigator was to record details of any health care utilization associated with unplanned visits to GP/Urologist. Responses to the following question were recorded: "Does the participant have any unscheduled GP/Urologist (outpatients) visits planned, not relating to the study (this can include visits resulting from UTI, UI, macroscopic haematuria, etc.?". If the answer to the question was “yes,” the number of visits was recorded.
Time Frame Every 3 months from Month 3 to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As study progressed, participants dropped out the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1550 1581 1564
Measure Type: Number
Unit of Measure: visits
Month 3, n=1550, 1581, 1564 27 27 30
Month 6, n=1479, 1516, 1514 23 29 33
Month 9, n=1439, 1465, 1477 12 27 26
Month 12, n=1400, 1431, 1434 30 28 29
Month 15, n=1343, 1386, 1381 19 28 32
Month 18, n=1318, 1350, 1328 23 21 34
Month 21, n=1281, 1326, 1287 20 27 26
Month 24, n=1263, 1293, 1244 29 23 26
Month 27, n=1233, 1262, 1206 13 12 16
Month 30, n=1222, 1221, 1166 10 16 10
Month 33, n=1202, 1199, 1128 6 13 20
Month 36, n=1187, 1174, 1095 8 12 18
Month 39, n=1160, 1144, 1055 12 10 18
Month 42, n=1149, 1126, 1035 15 9 15
Month 45, n=1129, 1110, 1009 5 7 8
Month 48, n=1113, 1093, 990 7 4 8
18.Secondary Outcome
Title Adjusted Mean Change From Baseline in BPH Impact Index (BII) at Months 12, 24, 36, and 48
Hide Description The BII is a 4-item questionnaire, score range of 0 (best) to 12 (worst) for questions 1-3, and 0 (best) to 13 (worst) for question 4, that assesses the overall impact of BPH on a participant's general sense of well being and measures aspects of physical discomfort, worry, and bother, all of which can be affected by BPH and its symptoms. BII score = sum of questions 1-4. Change from baseline = Post-Baseline Value. Estimates are based on the adjusted (least squares) means from the general linear model: change from baseline BII = treatment + cluster + baseline BII.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1574 1593 1582
Least Squares Mean (Standard Error)
Unit of Measure: points on a scale
Month 12 -1.9  (0.06) -1.5  (0.06) -1.6  (0.06)
Month 24 -2.1  (0.07) -1.7  (0.07) -1.5  (0.07)
Month 36 -2.2  (0.07) -1.8  (0.07) -1.3  (0.07)
Month 48 -2.2  (0.07) -1.8  (0.07) -1.2  (0.07)
19.Secondary Outcome
Title Adjusted Mean Change From Baseline in BPH-Related Health Status (BHS) at Months 12, 24, 36, and 48
Hide Description The effect of study treatment on BHS was assessed by using three self-administered questionnaires: the International Prostate Symptom Score (IPSS), the BPH Impact Index (BII), and Patient Perception of Study Medication (PPSM). The BHS score was collected on the IPPS questionnaire and ranged from 0 (best) to 6 (worst). Percent change from baseline = [(post-baseline – baseline)/baseline value] x 100. Estimates were based on the adjusted (least squares) means from the general linear model: change from baseline BPH-related health status = treatment + cluster + baseline BPH-Related health status.
Time Frame Baseline and Months 12, 24, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1575 1592 1583
Least Squares Mean (Standard Error)
Unit of Measure: points on a scale
Month 12 -1.2  (0.03) -1.0  (0.03) -1.0  (0.03)
Month 24 -1.4  (0.03) -1.1  (0.03) -1.1  (0.03)
Month 36 -1.5  (0.03) -1.2  (0.03) -1.1  (0.03)
Month 48 -1.5  (0.03) -1.3  (0.03) -1.1  (0.03)
20.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 1 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "Since you began taking the study medication, how has control of your urinary problems changed?".
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1685 1600 1586
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Improvement, n=1585, 1600, 1586 696 656 706
BL, No Change/Any Worsening, n=1585, 1600, 1586 889 944 880
Month (M) 12, Any Improvement, n=1576, 1593, 1581 1281 1171 1218
M12, No Change/Any Worsening, n=1576, 1593, 1581 295 422 363
M24, Any Improvement, n=1576, 1593, 1581 1273 1200 1195
M24, No Change/Any Worsening, n=1576, 1593, 1581 303 393 386
M36, Any Improvement, n=1576, 1593, 1581 1268 1203 1152
M36, No Change/Any Worsening, n=1576, 1593, 1581 308 390 429
M48, Any Improvement, n=1576, 1593, 1581 1278 1212 1138
M48, No Change/Any Worsening, n=1576, 1593, 1581 298 381 443
21.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 2 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "How satisfied are you with the effect of the study medication on control of your urinary problems?" Satisfact., satisfaction.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1587 1600 1583
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Satisfact., n=1587, 1600, 1583 707 652 686
BL, Neutral/Any Dissatisfact., n=1587, 1600, 1583 880 948 897
Month (M) 12, Any Satisfact., n=1576, 1593, 1581 1224 1127 1178
M12, Neutral/Any Dissatisfact., n=1576, 1593, 1581 352 466 403
M24, Any Satisfact., n=1576, 1593, 1581 1261 1166 1150
M24, Neutral/Any Dissatisfact., n=1576, 1593, 1581 315 427 431
M36, Any Satisfact., n=1576, 1593, 1581 1260 1167 1120
M36, Neutral/Any Dissatisfact., n=1576, 1593, 1581 316 426 461
M48, Any Satisfact., n=1576, 1593, 1581 1267 1172 1088
M48, Neutral/Any Dissatisfact., n=1576, 1593, 1581 309 421 493
22.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 3 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "Since you began taking the study medication, how has the strength of your urinary stream changed?".
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1585 1601 1585
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Improvement, n=1585, 1601, 1585 629 602 615
BL, No Change/Any Worsening, n=1585, 1601, 1585 956 999 970
Month (M) 12, Any Improvement, n=1576, 1593, 158 1181 1044 1105
M12, No Change/Any Worsening, n=1576, 1593, 1581 395 549 476
M24, Any Improvement, n=1576, 1593, 1581 1215 1070 1057
M24, No Change/Any Worsening, n=1576, 1593, 1581 361 523 524
M36, Any Improvement, n=1576, 1593, 1581 1206 1071 1023
M36, No Change/Any Worsening, n=1576, 1593, 1581 370 522 558
M48, Any Improvement, n=1576, 1593, 1581 1202 1086 1008
M48, No Change/Any Worsening, n=1576, 1593, 1581 374 507 573
23.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 4 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "How satisfied are you with the effect of the study medication on the strength of your urinary stream?". Satisfact., satisfaction.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1583 1601 1582
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Satisfact., n=1583,1601,1582 632 586 613
BL, Neutral/Any Dissatisfact., n=1583,1601,1582 951 1015 969
Month (M) 12, Any Satisfact., n=1576, 1593, 1581 1154 1037 1097
M12, Neutral/Any Dissatisfact., n=1576, 1593, 1581 422 556 484
M24, Any Satisfact., n=1576, 1593, 1581 1203 1072 1051
M24, Neutral/Any Dissatisfact., n=1576, 1593, 1581 373 521 530
M36, Any Satisfact., n=1576, 1593, 1581 1201 1075 1039
M36, Neutral/Any Dissatisfact., n=1576, 1593, 1581 375 518 542
M48, Any Satisfact., n=1576, 1593, 1581 1208 1089 1022
M48, Neutral/Any Dissatisfact., n=1576, 1593, 1581 368 504 559
24.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 5 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "Since you began taking the study medication, how has your pain prior to urinating changed?".
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 869 901 849
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Improvement, n=869, 901, 849 337 331 332
BL, No Change/Any Worsening, n=869, 901, 849 532 570 517
Month (M) 12, Any Improvement, n=769, 817, 771 556 526 527
M12, No Change/Any Worsening, n=769, 817, 771 213 291 244
M24, Any Improvement, n=720, 780, 771 537 526 535
M24, No Change/Any Worsening, n=720, 780, 771 183 254 236
M36, Any Improvement, n=714, 753, 748 540 514 496
M36, No Change/Any Worsening, n=714, 753, 748 174 239 252
M48, Any Improvement, n=709, 756, 751 531 510 489
M48, No Change/Any Worsening, n=709, 756, 751 178 246 262
25.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 6 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "How satisfied are you with the effect the study medication has on your pain prior to urinating?". Satisfact., satisfaction.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1135 1223 1161
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Satisfact., n=908, 932, 889 375 351 351
BL, Neutral/Any Dissatisfact., n=908, 932, 889 533 581 538
Month (M) 12, Any Satisfact., n=1022, 1088, 1019 712 672 681
M12, Neutral/Any Dissatisfact., n=1022, 1088, 1019 310 416 338
M24, Any Satisfact., n=1077, 1151, 1085 764 740 708
M24, Neutral/Any Dissatisfact., n=1077, 1151, 1085 313 411 377
M36, Any Satisfact., n=1115, 1200, 1135 799 785 736
M36, Neutral/Any Dissatisfact., n=1115, 1200, 1135 316 415 399
M48, Any Satisfact., n=1135, 1223, 1161 810 792 739
M48, Neutral/Any Dissatisfact., n=1135, 1223, 1161 325 431 422
26.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 7 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "Since you began taking the study medication, how has your pain during urination changed?".
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 852 889 822
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Improvement, n=852, 889, 822 321 314 319
BL, No Change/Any Worsening, n=852, 889, 822 531 575 503
Month (M) 12, Any Improvement, n=760, 781, 755 550 500 529
M12, No Change/Any Worsening, n=760, 781, 755 210 281 226
M24, Any Improvement, n=706, 760, 747 532 508 519
M24, No Change/Any Worsening, n=706, 760, 747 174 252 228
M36, Any Improvement, n=704, 741, 733 529 504 491
M36, No Change/Any Worsening, n=704, 741, 733 175 237 242
M48, No Change/Any Worsening, n=702, 739, 740 175 252 257
M48, Any Improvement, n=702, 739, 740 527 487 483
27.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 8 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "How satisfied are you with the effect the study medication has on your pain during urination?". Satisfact., satisfaction.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1146 1224 1160
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Satisfact., n=890, 925, 851 354 348 333
BL, Neutral/Any Dissatisfact., n=890, 925, 851 536 577 518
Month (M) 12, Any Satisfact., n=1022, 1088, 1011 712 655 678
M12, Neutral/Any Dissatisfact., n=1022, 1088, 1011 310 433 333
M24, Any Satisfact., n=1077, 1155, 1079 763 730 708
M24, Neutral/Any Dissatisfact., n=1077, 1155, 1079 314 425 371
M36, Any Satisfact., n=1121, 1206, 1131 807 784 724
M36, Neutral/Any Dissatisfact., n=1121, 1206, 1131 314 422 407
M48, Any Satsifact., n=1146,1224,1160 827 785 729
M48, Neutral/Any Dissatisfact., n=1146, 1224, 1160 319 439 431
28.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 9 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "Since you began taking the study medication, how has the way your urinary problems interfere with your ability to go about your usual activities changed?".
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1575 1593 1580
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Improvement, n=1574, 1599, 1575 509 481 494
BL, No Change/Any Worsening, n=1574, 1599, 1575 1065 1118 1081
Month (M) 12, Any Improvement, n=1575, 1593, 1580 1124 1027 1084
M12, No Change/Any Worsening, n=1575, 1593, 1580 451 566 496
M24, Any Improvement, n=1575, 1593, 1580 1146 1053 1049
M24, No Change/Any Worsening, n=1575, 1593, 1580 429 540 531
M36, Any Improvement, n=1575, 1593, 1580 1575 1593 1580
M36, No Change/Any Worsening, n=1575, 1593, 1580 412 529 553
M48, Any Improvement, n=1575, 1593, 1580 1148 1063 1008
M48, No Change/Any Worsening, n=1575, 1593, 1580 427 530 572
29.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 10 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "How satisfied are you with the effect the study medication has on your ability to go about your usual activities without interference from your urinary problems?". Satisfact., satisfaction.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1575 1593 1580
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Satisfact., n=1574, 1600, 1576 611 565 584
BL, Neutral /Any Dissatisfact., n=1574, 1600, 1576 963 1035 992
Month (M) 12, Any Satisfact., n=1575, 1593, 1580 1176 1073 1114
M12, Neutral/Any Dissatisfact., n=1575, 1593, 1580 399 520 466
M24, Any Satisfact., n=1575, 1593, 1580 1205 1116 1088
M24, Neutral/Any Dissatisfact., n=1575, 1593, 1580 370 477 492
M36, Any Satisfact., n=1575, 1593, 1580 1210 1098 1074
M36, Neutral/Any Dissatisfact., n=1575, 1593, 1580 365 495 506
M48, Any Satisfact., n=1575, 1593, 1580 1213 1123 1043
M48, Neutral/Any Dissatisfact., n=1575, 1593, 1580 362 470 537
30.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 11 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "Overall, how satisfied are you with the study medication and it's effect on your urinary problems?". Satisfact., satisfaction.
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1574 1592 1581
Measure Type: Number
Unit of Measure: participants
Baseline (BL), Any Satisfact., n=1573, 1598, 1574 717 683 699
BL, Neutral/Any Dissatisfact., n=1573, 1598, 1574 856 915 875
Month (M) 12, Any Satisfact., n=1574, 1592, 1581 150 1159 1202
M12, Neutral/Any Dissatisfact., n=1574, 1592, 1581 324 433 379
M24, Any Satisfact., n=1574, 1592, 1581 1279 1188 1163
M24, Neutral/Any Dissatisfact., n=1574, 1592, 1581 295 404 418
M36, Any Satisfact., n=1574, 1592, 1581 1270 1188 1119
M36, Neutral/Any Dissatisfact., n=1574, 1592, 1581 304 404 462
M48, Any Satifact., n=1574, 1592, 1581 1262 1182 1097
M48, Neutral/Any Dissatisfact., n=1574, 1592, 1581 312 410 484
31.Secondary Outcome
Title Patient Perception of Study Medication (PPSM): Number of Participants With the Indicated Responses to Question 12 (LOCF)
Hide Description This 12-item questionnaire (PPSM) was developed by GlaxoSmithKline for use in this study and was designed to quantify the participant's perceptions and satisfaction with the effect of study treatment on control of their urinary symptoms at baseline and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48. Participants were asked to respond to the question of "Would you ask your doctor for the medication you received in this study?".
Time Frame Baseline and Months 12, 24, 36, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. As the study progressed, participants dropped out of the study. Only participants responding to the question were analyzed.
Arm/Group Title Dutasteride 0.5 mg Plus Tamsulosin 0.4 mg Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description:
Dutasteride 0.5 milligrams (mg) plus tamsulosin 0.4 mg once daily for 208 weeks
Dutasteride 0.5 mg plus tamsulosin placebo once daily for 208 weeks
Tamsulosin 0.4 mg plus dutasteride placebo once daily for 208 weeks
Overall Number of Participants Analyzed 1574 1592 1581
Measure Type: Number
Unit of Measure: participants
Baseline, Yes, n=1560, 1579, 1562 587 557 582
Baseline, No/Not Sure, n=1560, 1579, 1562 973 1022 980
Month 12, Yes, n=1574, 1592, 1581 972 920 970
Month 12, No/Not Sure, n=1574, 1592, 1581 602 671 611
Month 24, Yes, n=1574, 1592, 1581 1027 955 952
Month 24, No/Not Sure, n=1574, 1592, 1581 547 636 629
Month 36, Yes, n=1574, 1592, 1581 1031 956 915
Month 36, No/Not Sure, n=1574, 1592, 1581 543 636 666
Month 48, Yes, n=1574, 1592, 1581 1003 918 874
Month 48, No/Not Sure, n=1574, 1592, 1581 571 674 707
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Combination Dutasteride 0.5 mg Tamsulosin 0.4 mg
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified]
All-Cause Mortality
Combination Dutasteride 0.5 mg Tamsulosin 0.4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Combination Dutasteride 0.5 mg Tamsulosin 0.4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   303/1610 (18.82%)   339/1623 (20.89%)   348/1611 (21.60%) 
Blood and lymphatic system disorders       
Anaemia  1  0/1610 (0.00%)  2/1623 (0.12%)  1/1611 (0.06%) 
Granulocytopenia  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Haemolytic anaemia  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Idiopathic thrombocytopenic purpura  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Lymphadenopathy  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pernicious anaemia  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Thrombocytopenia  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Cardiac disorders       
Myocardial infarction  1  16/1610 (0.99%)  25/1623 (1.54%)  20/1611 (1.24%) 
Coronary artery disease  1  14/1610 (0.87%)  14/1623 (0.86%)  15/1611 (0.93%) 
Angina pectoris  1  14/1610 (0.87%)  14/1623 (0.86%)  15/1611 (0.93%) 
Atrial fibrillation  1  11/1610 (0.68%)  7/1623 (0.43%)  9/1611 (0.56%) 
Acute myocardial infarction  1  7/1610 (0.43%)  1/1623 (0.06%)  3/1611 (0.19%) 
Cardiac failure  1  5/1610 (0.31%)  1/1623 (0.06%)  5/1611 (0.31%) 
Coronary artery stenosis  1  4/1610 (0.25%)  5/1623 (0.31%)  2/1611 (0.12%) 
Myocardial ischaemia  1  3/1610 (0.19%)  3/1623 (0.18%)  3/1611 (0.19%) 
Angina unstable  1  1/1610 (0.06%)  3/1623 (0.18%)  4/1611 (0.25%) 
Supraventricular tachycardia  1  1/1610 (0.06%)  2/1623 (0.12%)  4/1611 (0.25%) 
Acute coronary syndrome  1  3/1610 (0.19%)  3/1623 (0.18%)  1/1611 (0.06%) 
Bradycardia  1  3/1610 (0.19%)  2/1623 (0.12%)  0/1611 (0.00%) 
Cardiac failure congestive  1  4/1610 (0.25%)  0/1623 (0.00%)  1/1611 (0.06%) 
Coronary artery occlusion  1  1/1610 (0.06%)  3/1623 (0.18%)  1/1611 (0.06%) 
Sick sinus syndrome  1  1/1610 (0.06%)  4/1623 (0.25%)  0/1611 (0.00%) 
Arrhythmia  1  0/1610 (0.00%)  3/1623 (0.18%)  1/1611 (0.06%) 
Atrial flutter  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Cardiac arrest  1  2/1610 (0.12%)  0/1623 (0.00%)  1/1611 (0.06%) 
Mitral valve incompetence  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Ventricular extrasystoles  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Aortic valve incompetence  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Cardio-respiratory arrest  1  2/1610 (0.12%)  0/1623 (0.00%)  0/1611 (0.00%) 
Pericarditis  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Ventricular tachycardia  1  1/1610 (0.06%)  1/1623 (0.06%)  0/1611 (0.00%) 
Coronary artery insufficiency  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Aortic valve disease mixed  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Arteriosclerosis coronary artery  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Atrioventricular block  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Atrioventricular block complete  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
AV dissociation  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Cardiac asthma  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Cardiac failure chronic  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Coronary artery aneurysm  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Coronary artery thrombosis  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Left ventricular failure  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Mitral valve prolapse  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Tachycardia  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Tricuspid valve incompetence  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Cardiovascular deconditioning  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Cardiopulmonary failure  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Congestive cardiomyopathy  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Hypertensive cardiomyopathy  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Cardiac valve disease  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Acute left ventricular failure  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Chronic left ventricular failure  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Acute myeloid leukaemia  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Pericardial effusion  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Cardiac tamponade  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Congenital, familial and genetic disorders       
Hydrocele  1  2/1610 (0.12%)  0/1623 (0.00%)  0/1611 (0.00%) 
Aplasia  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Hereditary sideroblastic anaemia  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Ear and labyrinth disorders       
Deafness  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Vertigo  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Vestibular disorder  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Sudden hearing loss  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Endocrine disorders       
Goitre  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Eye disorders       
Cataract  1  2/1610 (0.12%)  2/1623 (0.12%)  4/1611 (0.25%) 
Retinal detachment  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Macular degeneration  1  1/1610 (0.06%)  0/1623 (0.00%)  2/1611 (0.12%) 
Eye haemorrhage  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Glaucoma  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Retinal tear  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Vitreous haemorrhage  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gastrointestinal disorders       
Inguinal hernia  1  4/1610 (0.25%)  17/1623 (1.05%)  11/1611 (0.68%) 
Abdominal pain  1  5/1610 (0.31%)  1/1623 (0.06%)  2/1611 (0.12%) 
Colonic polyp  1  1/1610 (0.06%)  4/1623 (0.25%)  1/1611 (0.06%) 
Gastric ulcer  1  2/1610 (0.12%)  1/1623 (0.06%)  1/1611 (0.06%) 
Pancreatitis  1  2/1610 (0.12%)  0/1623 (0.00%)  2/1611 (0.12%) 
Pancreatitis acute  1  1/1610 (0.06%)  1/1623 (0.06%)  2/1611 (0.12%) 
Abdominal hernia  1  1/1610 (0.06%)  1/1623 (0.06%)  2/1611 (0.12%) 
Haemorrhoids  1  0/1610 (0.00%)  1/1623 (0.06%)  2/1611 (0.12%) 
Ileus  1  0/1610 (0.00%)  2/1623 (0.12%)  1/1611 (0.06%) 
Rectal haemorrhage  1  1/1610 (0.06%)  2/1623 (0.12%)  0/1611 (0.00%) 
Abdominal pain upper  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Anal fissure  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Duodenal ulcer  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Duodenal ulcer haemorrhage  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Gastric haemorrhage  1  1/1610 (0.06%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gastric ulcer haemorrhage  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Gastritis  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Gastrooesophageal reflux disease  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Gastrointestinal haemorrhage  1  0/1610 (0.00%)  1/1623 (0.06%)  2/1611 (0.12%) 
Inguinal hernia, obstructive  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Intestinal obstruction  1  1/1610 (0.06%)  1/1623 (0.06%)  0/1611 (0.00%) 
Rectal polyp  1  2/1610 (0.12%)  0/1623 (0.00%)  0/1611 (0.00%) 
Abdominal distension  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Abdominal rigidity  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Anal fistula  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Barrett's oesophagus  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Colitis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Crohn's disease  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Diarrhoea  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Diverticulum  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Diverticulum intestinal  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Duodenitis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Dysphagia  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Gastric ulcer perforation  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Gastritis haemorrhagic  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Haematemesis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Haematochezia  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Large intestine perforation  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Mallory-Weiss syndrome  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Melaena  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Oesophagitis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Peptic ulcer haemorrhage  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Peritonitis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Proctitis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Small intestinal obstruction  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Umbilical hernia  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Volvulus  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Vomiting  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Lower gastrointestinal haemorrhage  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Mechanical ileus  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pharyngoesophageal diverticulum  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Intestinal haemorrhage  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Appendix disorder  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Intra-abdominal haemorrhage  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Bowel movement irregularity  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Erosive oesophagitis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Anal prolapse  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Inguinal hernia strangulated  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
General disorders       
Pyrexia  1  1/1610 (0.06%)  2/1623 (0.12%)  3/1611 (0.19%) 
Non-cardiac chest pain  1  2/1610 (0.12%)  4/1623 (0.25%)  0/1611 (0.00%) 
Chest pain  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Multi-organ failure  1  1/1610 (0.06%)  1/1623 (0.06%)  2/1611 (0.12%) 
Death  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Asthenia  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Fatigue  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Generalised oedema  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Local swelling  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Malaise  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Sudden death  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Implant site erosion  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Hepatobiliary disorders       
Cholelithiasis  1  4/1610 (0.25%)  6/1623 (0.37%)  6/1611 (0.37%) 
Cholecystitis acute  1  3/1610 (0.19%)  3/1623 (0.18%)  4/1611 (0.25%) 
Cholecystitis  1  3/1610 (0.19%)  2/1623 (0.12%)  0/1611 (0.00%) 
Bile duct stone  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Cholecystitis chronic  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Jaundice  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Cholangitis acute  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Hepatitis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Hydrocholecystis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Hepatic mass  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Infections and infestations       
Pneumonia  1  13/1610 (0.81%)  10/1623 (0.62%)  6/1611 (0.37%) 
Urniary tract infection  1  3/1610 (0.19%)  1/1623 (0.06%)  3/1611 (0.19%) 
Cellulitis  1  3/1610 (0.19%)  3/1623 (0.18%)  0/1611 (0.00%) 
Sepsis  1  1/1610 (0.06%)  2/1623 (0.12%)  3/1611 (0.19%) 
Bronchitis  1  2/1610 (0.12%)  0/1623 (0.00%)  3/1611 (0.19%) 
Diverticulitis  1  0/1610 (0.00%)  3/1623 (0.18%)  2/1611 (0.12%) 
Lobar pneumonia  1  1/1610 (0.06%)  2/1623 (0.12%)  1/1611 (0.06%) 
Urosepis  1  1/1610 (0.06%)  0/1623 (0.00%)  3/1611 (0.19%) 
Bronchopneumonia  1  2/1610 (0.12%)  0/1623 (0.00%)  1/1611 (0.06%) 
Upper respiratory tract infection  1  0/1610 (0.00%)  1/1623 (0.06%)  2/1611 (0.12%) 
Appendicitis  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Septic shock  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Viral infection  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Arthritis bacterial  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Respiratory tract infection  1  0/1610 (0.00%)  0/1623 (0.00%)  2/1611 (0.12%) 
Device related infection  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Abcess intestinal  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Amoebiasis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Bronchiectasis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Carbuncle  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Chronic sinusitis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Cystitis  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Dengue fever  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Ear infection  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Endocarditis bacterial  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Epiglottitis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gangrene  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gastroenteritis  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Gastroenteritis Escherichia coli  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gastroenteritis salmonella  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Infective myositis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Localised infection  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Nasopharyngitis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Orchitis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Osteomyelitis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pneumonia streptococcal  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Prostatic abscess  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pyelonephritis acute  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Salmonellosis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Subcutaneous abscess  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Tinea pedis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Wound infection  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Anal abscess  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Streptococcal sepsis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Postoperative abscess  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Escherichia urinary tract infection  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Central line infection  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pseudomonal sepsis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Implant site infection  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pseudomonas infection  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Biliary tract infection  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Epidemic nephropathy  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Cholecystitis infective  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Cellulitis of male external genital organ  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Post procedural sepsis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Gastroenteritis norovirus  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Injury, poisoning and procedural complications       
Femur fracture  1  4/1610 (0.25%)  1/1623 (0.06%)  1/1611 (0.06%) 
Hip fracture  1  3/1610 (0.19%)  1/1623 (0.06%)  2/1611 (0.12%) 
Tibia fracture  1  3/1610 (0.19%)  0/1623 (0.00%)  2/1611 (0.12%) 
Head injury  1  2/1610 (0.12%)  1/1623 (0.06%)  1/1611 (0.06%) 
Road traffic accident  1  1/1610 (0.06%)  1/1623 (0.06%)  2/1611 (0.12%) 
Subdural haematoma  1  0/1610 (0.00%)  1/1623 (0.06%)  3/1611 (0.19%) 
Tendon rupture  1  1/1610 (0.06%)  1/1623 (0.06%)  2/1611 (0.12%) 
Cartilage injury  1  1/1610 (0.06%)  2/1623 (0.12%)  0/1611 (0.00%) 
Fibula fracture  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Multiple injuries  1  0/1610 (0.00%)  1/1623 (0.06%)  2/1611 (0.12%) 
Rib fracture  1  1/1610 (0.06%)  0/1623 (0.00%)  2/1611 (0.12%) 
Spinal fracture  1  0/1610 (0.00%)  2/1623 (0.12%)  1/1611 (0.06%) 
Cervical vertebral fracture  1  1/1610 (0.06%)  2/1623 (0.12%)  0/1611 (0.00%) 
Contusion  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Post procedural haemorrhage  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Wound  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Concussion  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Radius fracture  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Spinal compression fracture  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Sternal fracture  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Ulna fracture  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Wound dehiscence  1  1/1610 (0.06%)  1/1623 (0.06%)  0/1611 (0.00%) 
Lumbar vertebral fracture  1  2/1610 (0.12%)  0/1623 (0.00%)  0/1611 (0.00%) 
Accidental overdose  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Ankle fracture  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Carbon monoxide poisoning  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Cardiac pacemaker malfunction  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Clavicle fracture  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Epicodylitis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Extradural haematoma  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Fall  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gun shot wound  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Hand fracture  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Injury  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Muscle rupture  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Patella fracture  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Seroma  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Wrist fracture  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Anaemia postoperative  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Vascular pseudoaneurysm  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Vascular graft occlusion  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Face injury  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Postoperative ileus  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Device failure  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Medical device complicaiton  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Procedural complication  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Skin laceration  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Traumatic brain injury  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Joint injury  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pelvic fracture  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Limb injury  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Lung injury  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Skull fracture  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Chest injury  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Upper limb fracture  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Limb traumatic amputation  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Lower limb fracture  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Procedural hypotension  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Post procedural haematoma  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Post procedural constipation  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Traumatic haematoma  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Investigations       
Alanine aminotransferase increased  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Aspartate aminotransferase increased  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Chest x-ray abnormal  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Coagulation factor decreased  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Electrocardiogram abnormal  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Heart rate irregular  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Intraocular pressure increased  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Prostatic specific antigen increased  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Blood alkaline phosphatase increased  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  3/1610 (0.19%)  2/1623 (0.12%)  0/1611 (0.00%) 
Hyponatraemia  1  1/1610 (0.06%)  2/1623 (0.12%)  2/1611 (0.12%) 
Diabetes mellitus inadequate control  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Hypercalcaemia  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Hyperkalaemia  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  9/1610 (0.56%)  13/1623 (0.80%)  11/1611 (0.68%) 
Intervertebral disc protrusion  1  1/1610 (0.06%)  6/1623 (0.37%)  1/1611 (0.06%) 
Rotator cuff syndrome  1  2/1610 (0.12%)  3/1623 (0.18%)  2/1611 (0.12%) 
Arthralgia  1  2/1610 (0.12%)  1/1623 (0.06%)  3/1611 (0.19%) 
Spinal column stenosis  1  1/1610 (0.06%)  1/1623 (0.06%)  4/1611 (0.25%) 
Arthritis  1  2/1610 (0.12%)  1/1623 (0.06%)  0/1611 (0.00%) 
Back pain  1  2/1610 (0.12%)  1/1623 (0.06%)  0/1611 (0.00%) 
Flank pain  1  1/1610 (0.06%)  1/1623 (0.06%)  0/1611 (0.00%) 
Lumbar spinal stenosis  1  1/1610 (0.06%)  1/1623 (0.06%)  0/1611 (0.00%) 
Cervical spinal stenosis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Muscular weakness  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Neck pain  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Osteoporosis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Polymyalgia rheumatica  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Psoriatic arthropathy  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Rheumatoid arthritis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Spinal osteoarthritis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Musculoskeletal discomfort  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Foot deformity  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Intervertebral disc degeneration  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Nose deformity  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Spondylolisthesis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Prostate cancer  1  21/1610 (1.30%)  17/1623 (1.05%)  25/1611 (1.55%) 
Colon cancer  1  6/1610 (0.37%)  9/1623 (0.55%)  5/1611 (0.31%) 
Bladder cancer  1  6/1610 (0.37%)  6/1623 (0.37%)  4/1611 (0.25%) 
Lung neoplasm malignant  1  3/1610 (0.19%)  2/1623 (0.12%)  5/1611 (0.31%) 
Hepatic neoplasm malignant  1  1/1610 (0.06%)  2/1623 (0.12%)  2/1611 (0.12%) 
Lymphoma  1  1/1610 (0.06%)  1/1623 (0.06%)  3/1611 (0.19%) 
Malignant melanoma  1  2/1610 (0.12%)  1/1623 (0.06%)  2/1611 (0.12%) 
Pancreatic carcinoma  1  4/1610 (0.25%)  0/1623 (0.00%)  2/1611 (0.12%) 
Rectal cancer  1  1/1610 (0.06%)  3/1623 (0.18%)  1/1611 (0.06%) 
Bladder transitional cell carcinoma  1  1/1610 (0.06%)  2/1623 (0.12%)  1/1611 (0.06%) 
Metastases to liver  1  0/1610 (0.00%)  3/1623 (0.18%)  1/1611 (0.06%) 
Colon neoplasm  1  3/1610 (0.19%)  0/1623 (0.00%)  1/1611 (0.06%) 
Renal cell carcinoma  1  1/1610 (0.06%)  3/1623 (0.18%)  0/1611 (0.00%) 
Gastric cancer  1  0/1610 (0.00%)  3/1623 (0.18%)  0/1611 (0.00%) 
Myeloid leukaemia  1  1/1610 (0.06%)  0/1623 (0.00%)  2/1611 (0.12%) 
Renal cancer  1  0/1610 (0.00%)  0/1623 (0.00%)  3/1611 (0.19%) 
Brain neoplasm  1  0/1610 (0.00%)  0/1623 (0.00%)  3/1611 (0.19%) 
Basal cell carcinoma  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Bladder neoplasm  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Bronchial carcinoma  1  1/1610 (0.06%)  1/1623 (0.06%)  0/1611 (0.00%) 
Lung adenocarcinoma  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Oesophageal carcinoma  1  1/1610 (0.06%)  0/1623 (0.00%)  1/1611 (0.06%) 
Thyroid neoplasm  1  0/1610 (0.00%)  0/1623 (0.00%)  2/1611 (0.12%) 
Pancreatic neolasm  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Adenocarcinoma  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Benign colonic neoplasm  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Bladder cancer recurrent  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Brain neoplasm benign  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Brain neoplasm malignant  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Central nervous system lymphoma  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Gallbladder cancer  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gastrointestinal carcinoma  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Glioblastoma multiforme  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Laryngeal cancer  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Malignant neoplasm of ampulla of Vater  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Malignant palate neoplasm  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Mesothelioma  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Metastases to bone  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Metastases to lung  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Metastatic pain  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Multiple myeloma  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Neoplasm malignant  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Non-small cell lung cancer stage I  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Pancreatic carcinoma metastatic  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Prostate cancer stage I  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Retinal melanoma  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Squamous cell carcinoma  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Tonsil cancer  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Tracheal cancer  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Transitional cell carcinoma  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Renal oncocytoma  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Urinary bladder adenoma  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Gastrointestinal cancer metastatic  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Hepatic cancer metastatic  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Colon cancer metastatic  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Retroperitoneal neoplasm  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Large intestine carcinoma  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Metastases to central nervous system  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Metastatic neoplasm  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Urinary tract neoplasm  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Colorectal cancer  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Salivary gland cancer  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Gastric neoplasm  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Metastatic squamous cell carcinoma  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Thyroid cancer  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Bladder transitional cell carcinoma stage II  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Bladder transitional cell carcinoma stage III  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Brain stem ischaemia  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Cholesteatoma  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  11/1610 (0.68%)  15/1623 (0.92%)  8/1611 (0.50%) 
Transient ischaemic attack  1  5/1610 (0.31%)  5/1623 (0.31%)  4/1611 (0.25%) 
Syncope  1  6/1610 (0.37%)  1/1623 (0.06%)  3/1611 (0.19%) 
Cerebral infarction  1  1/1610 (0.06%)  4/1623 (0.25%)  3/1611 (0.19%) 
Ischaemic stroke  1  1/1610 (0.06%)  0/1623 (0.00%)  4/1611 (0.25%) 
Cerebral ischaemia  1  3/1610 (0.19%)  0/1623 (0.00%)  1/1611 (0.06%) 
Dizziness  1  1/1610 (0.06%)  2/1623 (0.12%)  1/1611 (0.06%) 
Carotid artery stenosis  1  1/1610 (0.06%)  1/1623 (0.06%)  1/1611 (0.06%) 
Cerebral haemorrhage  1  0/1610 (0.00%)  1/1623 (0.06%)  2/1611 (0.12%) 
Convulsion  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Epilepsy  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Grand mal convulsions  1  0/1610 (0.00%)  1/1623 (0.06%)  1/1611 (0.06%) 
Loss of consciousness  1  2/1610 (0.12%)  0/1623 (0.00%)  0/1611 (0.00%) 
Balance disorder  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Parkinson's disease  1  0/1610 (0.00%)  2/1623 (0.12%)  0/1611 (0.00%) 
Altered state of consciousness  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Autonomic nervous system imbalance  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Dementia Alzheimer's type  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Dysarthria  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Encephalopathy  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Extrapyramidal disorder  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Haemorrhage intracranial  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Hemiparesis  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Monoplegia  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Multiple sclerosis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Neuritis  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Presyncope  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Psychomotor hyperactivity  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Sciatica  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Senile dementia  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Somnolence  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Thrombotic stroke  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Carotid artery occlusion  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Intracranial hypotension  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Lumbar radiculopathy  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Radicular pain  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Ischaemic cerebral infarction  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Cerebral cyst  1  0/1610 (0.00%)  1/1623 (0.06%)  0/1611 (0.00%) 
Nerve root compression  1  1/1610 (0.06%)  0/1623 (0.00%)  0/1611 (0.00%) 
Cerebral arteriosclerosis  1  0/1610 (0.00%)  0/1623 (0.00%)  1/1611 (0.06%) 
Psychiatric disorders       
Depression  1