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Trial record 12 of 10929 for:    Placebo AND once

Phase 3 Study of Tadalafil Once-Daily in Asian Men With Benign Prostatic Hyperplasia (BPH)

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ClinicalTrials.gov Identifier: NCT01460342
Recruitment Status : Completed
First Posted : October 26, 2011
Results First Posted : September 25, 2013
Last Update Posted : September 25, 2013
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Benign Prostatic Hyperplasia
Interventions Drug: Tadalafil
Drug: Placebo
Enrollment 610
Recruitment Details  
Pre-assignment Details The study consisted of 3 periods: a screening/wash-out period (pre-randomization, 1 day up to 4 weeks), a placebo lead-in period (pre-randomization, 4 weeks, participant-blinded), and a double-blind treatment period (post-randomization, 12 weeks).
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period. Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Period Title: Overall Study
Started 304 306
Received at Least 1 Dose of Study Drug 304 306
Completed 293 292
Not Completed 11 14
Reason Not Completed
Adverse Event             5             4
Lost to Follow-up             1             2
Protocol Violation             0             1
Withdrawal by Subject             3             4
Physician Decision             1             3
Lack of Efficacy             1             0
Arm/Group Title Placebo Tadalafil Total
Hide Arm/Group Description Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period. Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily]. Total of all reporting groups
Overall Number of Baseline Participants 304 306 610
Hide Baseline Analysis Population Description
All randomized participants.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 304 participants 306 participants 610 participants
60.9  (8.1) 60.8  (7.7) 60.9  (7.9)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
<65 years 201 198 399
>=65 years 103 108 211
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
304
 100.0%
306
 100.0%
610
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Asian Number Analyzed 304 participants 306 participants 610 participants
304 306 610
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Japan 222 227 449
Korea, Republic of 82 79 161
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms per square meter (kg/m^2)
Number Analyzed 304 participants 306 participants 610 participants
24.1  (2.9) 24.0  (3.0) 24.0  (3.0)
[1]
Measure Description: BMI was an estimate of body fat based on body weight divided by height squared.
Current Tobacco Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Yes 55 57 112
No 249 249 498
Alcohol Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Yes 196 206 402
No 108 100 208
Benign Prostatic Hyperplasia (BPH) Severity   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Mild (IPSS Total Score 0 to 7) 5 6 11
Moderate (IPSS Total Score 8 to 19) 167 166 333
Severe (IPSS Total Score >=20) 132 134 266
[1]
Measure Description: BPH severity rated mild [an International Prostate Symptom Score (IPSS) Total Score from 0 to 7], moderate (IPSS Total Score from 8 to 19), or severe (an IPSS Total Score >=20). The IPSS Total Score was the sum of Questions 1 through 7 in the IPSS questionnaire. Each question was based on the participant's urination experiences and prostate symptoms during the last month. Scores ranged from 0 (none/no symptoms) to 5 (frequent symptoms) for an IPSS Total Score that ranged from 0 to 35; higher numerical scores represented a greater severity of symptoms.
Duration of BPH  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 304 participants 306 participants 610 participants
4.0  (3.3) 4.1  (3.2) 4.0  (3.2)
Patient Global Impression of Severity (PGI-S) Scale   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Normal 0 0 0
Mild 67 64 131
Moderate 187 195 382
Severe 50 47 97
[1]
Measure Description: The PGI-S Scale measured the participant's perception of severity of illness at the time of assessment. Scores were 1 (Normal), 2 (Mild), 3 (Moderate), and 4 (Severe).
Clinical Global Impression of Severity (CGI-S) Scale   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Normal 0 0 0
Mild 33 41 74
Moderate 218 211 429
Severe 53 54 107
[1]
Measure Description: The CGI-S Scale measured the clinician's perception of severity of illness at the time of the assessment. Scores were 1 (Normal), 2 (Mild), 3 (Moderate), and 4 (Severe).
Previous Alpha-Blocker Therapy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Yes 43 39 82
No 261 267 528
[1]
Measure Description: Previous alpha-blocker therapy during the 12 months prior to study enrollment.
Previous Benign Prostatic Hyperplasia - Lower Urinary Tract Symptoms (BPH-LUTS) Therapy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 304 participants 306 participants 610 participants
Yes 21 22 43
No 283 284 567
[1]
Measure Description: Previous BPH-LUTS therapy during the 12 months prior to study enrollment. Alpha-blocker therapy excluded.
Postvoid Residual Volume (PVR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliliters (mL)
Number Analyzed 304 participants 306 participants 610 participants
32.7  (50.0) 26.9  (37.7) 29.8  (44.3)
[1]
Measure Description: PVR was defined as the volume of urine remaining in the bladder after voiding, estimated by ultrasound.
Prostate Volume   [1] 
Mean (Standard Deviation)
Unit of measure:  mL
Number Analyzed 304 participants 306 participants 610 participants
31.6  (9.5) 30.7  (8.5) 31.1  (9.0)
[1]
Measure Description: The volume of prostate, estimated by transabdominal or transrectal ultrasound.
1.Primary Outcome
Title Change From Baseline in Total Score of International Prostate Symptom Score (IPSS) at 12 Weeks
Hide Description The IPSS Total Score was the sum of Questions 1 through 7 in the IPSS questionnaire. Each question was based on the participant's urination experiences and prostate symptoms during the last month. Scores ranged from 0 (none/no symptoms) to 5 (frequent symptoms) for an IPSS Total Score that ranged from 0 to 35; higher numerical scores represented a greater severity of symptoms. Least squares (LS) mean was based on the mixed-effect model repeated measures (MMRM) model analysis with participants as random effects, treatment, prior alpha-blocker use (yes/no), country (Japan/Korea), visit, and treatment-by-visit interaction as fixed effects, and baseline value and placebo lead-in total IPSS change as fixed covariates.
Time Frame Baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had non-missing data at baseline.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 301 305
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.5  (0.4) -6.0  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
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 Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.4 to -0.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Total Score of International Prostate Symptom Score (IPSS)
Hide Description The IPSS Total Score was the sum of Questions 1 through 7 in the IPSS questionnaire. Each question was based on the participant's urination experiences and prostate symptoms during the last month. Scores ranged from 0 (none/no symptoms) to 5 (frequent symptoms) for an IPSS Total Score that ranged from 0 to 35; higher numerical scores represented a greater severity of symptoms. Least squares (LS) mean was based on the mixed-effect model repeated measures (MMRM) model analysis with participants as random effects, treatment, prior alpha-blocker use (yes/no), country (Japan/Korea), visit, and treatment-by-visit interaction as fixed effects, and baseline value and placebo lead-in total IPSS change as fixed covariates.
Time Frame Baseline, 4 weeks, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had non-missing data at baseline.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 301 305
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Week 4 -2.8  (0.3) -4.0  (0.4)
Change at Week 8 -4.0  (0.4) -5.2  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is for the change from baseline in the IPSS Total Score at Week 4.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.0 to -0.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments The p-value is for the change from baseline in the IPSS Total Score at Week 8.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.0 to -0.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore
Hide Description The IPSS Storage (Irritative) Subscore was the sum of Questions 2, 4, and 7 in the IPSS questionnaire. Each question was scored from 0 (no irritative symptoms) to 5 (frequent irritative symptoms) for an IPSS Storage (Irritative) Subscore that ranged from 0 to 15; higher numerical scores represented a greater severity of symptoms. Least squares (LS) mean was based on the mixed-effect model repeated measures (MMRM) model analysis with participants as random effects, treatment, prior alpha-blocker use (yes/no), country (Japan/Korea), visit, and treatment-by-visit interaction as fixed effects, and baseline value and placebo lead-in total IPSS change as fixed covariates.
Time Frame Baseline, 4 weeks, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had non-missing data at baseline.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 301 305
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at 4 Weeks -0.9  (0.1) -1.2  (0.2)
Change at 8 Weeks -1.3  (0.2) -1.7  (0.2)
Change at 12 Weeks -1.4  (0.2) -2.0  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.090
Comments The p-value was for the change from baseline in the IPSS Storage (Irritative) Subscore at Week 4.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.6 to 0.0
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments The p-value was for the change from baseline in the IPSS Storage (Irritative) Subscore at Week 8.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.8 to -0.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments The p-value was for the change from baseline in the IPSS Storage (Irritative) Subscore at Week 12.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-0.9 to -0.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore
Hide Description The IPSS Voiding (Obstructive) Subscore was the sum of Questions 1, 3, 5, and 6 in the IPSS questionnaire. Each question was scored from 0 (no obstructive symptoms) to 5 (frequent obstructive symptoms) for an IPSS Voiding (Obstructive) Subscore that ranged from 0 to 20; higher numerical scores represented a greater severity of symptoms. Least squares (LS) mean was based on the mixed-effect model repeated measures (MMRM) model analysis with participants as random effects, treatment, prior alpha-blocker use (yes/no), country (Japan/Korea), visit, and treatment-by-visit interaction as fixed effects, and baseline value and placebo lead-in total IPSS change as fixed covariates.
Time Frame Baseline, 4 weeks, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had non-missing data at baseline.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 301 305
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Week 4 -1.8  (0.2) -2.8  (0.2)
Change at Week 8 -2.6  (0.3) -3.4  (0.3)
Change at Week 12 -3.1  (0.3) -4.0  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value was for the change from baseline in the IPSS Voiding (Obstructive) Subscore at Week 4.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.5 to -0.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments The p-value was for the change from baseline in the IPSS Voiding (Obstructive) Subscore at Week 8.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-1.3 to -0.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments The p-value was for the change from baseline in the IPSS Voiding (Obstructive) Subscore at Week 12.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.5 to -0.3
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in the International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index
Hide Description The IPSS QoL Index assessed the participant's response to the following question, "If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?". Response options were 0 (Delighted), 1 (Pleased), 2 (Mostly satisfied), 3 (Mixed, about equally satisfied and dissatisfied), 4 (Mostly dissatisfied), 5 (Unhappy), and 6 (Terrible), for a QoL Index Score that ranged from 0 to 6. Least squares (LS) mean was based on the mixed-effect model repeated measures (MMRM) model analysis with participants as random effects, treatment, prior alpha-blocker use (yes/no), country (Japan/Korea), visit, and treatment-by-visit interaction as fixed effects, and baseline value and placebo lead-in total IPSS change as fixed covariates.
Time Frame Baseline, 4 weeks, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had non-missing data at baseline.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 301 305
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Week 4 -0.5  (0.1) -0.6  (0.1)
Change at Week 8 -0.7  (0.1) -0.8  (0.1)
Change at Week 12 -0.9  (0.1) -1.1  (0.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.277
Comments The p-value was for the change from baseline in the IPSS QoL Index Score at Week 4.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.170
Comments The p-value was for the change from baseline in the IPSS QoL Index Score at Week 8.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments The p-value was for the change from baseline in the IPSS QoL Index Score at Week 12.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to -0.0
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Patient Global Impression of Improvement (PGI-I) Scale at 12 Weeks
Hide Description The PGI-I scale measured the participant's perception of improvement at the time of assessment compared with the start of treatment. Scores were 1 (Very much better), 2 (Much improved), 3 (Minimally improved), 4 (No change), 5 (Minimally worse), 6 (Much worse), and 7 (Very much worse).
Time Frame 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 304 306
Measure Type: Number
Unit of Measure: participants
Very Much Better 9 18
Much Better 55 79
A Little Better 138 148
No Change 90 55
A Little Worse 7 2
Much Worse 0 0
Very Much Worse 2 0
Missing 3 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value was from the Cochran-Mantel-Haenszel test adjusted for baseline severity of benign prostatic hyperplasia lower urinary tract symptoms (BPH-LUTS) and previous alpha-blocker therapy.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Secondary Outcome
Title Clinician Global Impression of Improvement (CGI-I) Scale at 12 Weeks
Hide Description The CGI-I measured the clinician's perception of participant improvement at the time of assessment compared with the start of treatment. Scores were 1 (Very much better), 2 (Much improved), 3 (Minimally improved), 4 (No change), 5 (Minimally worse), 6 (Much worse), and 7 (Very much worse).
Time Frame 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 304 306
Measure Type: Number
Unit of Measure: participants
Very Much Improved 10 14
Much Improved 74 103
Minimally Improved 115 125
No Change 93 59
Minimally Worse 8 1
Much Worse 0 0
Very Much Worse 1 0
Missing 3 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value was from the Cochran-Mantel-Haenszel test adjusted for baseline severity of benign prostatic hyperplasia lower urinary tract symptoms (BPH-LUTS) and previous alpha-blocker therapy.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Modified International Prostate Symptom Score (mIPSS) Score at 2 Weeks
Hide Description The mIPSS Total Score was the sum of Questions 1 through 7 in the mIPSS questionnaire, which was a modified version of the IPSS questionnaire. Questions about the participant's urination experiences and prostate symptoms in the IPSS questionnaire were modified to obtain responses based on time since the last visit rather than during the last month. Each question was scored from 0 (none/no symptoms) to 5 (frequent symptoms) for an mIPSS Total Score that ranged from 0 to 35; higher numerical scores represented a greater severity of symptoms. Least squares (LS) mean was based on the analysis of covariance (ANCOVA) model with treatment, prior alpha-blocker use (yes/no), and country (Japan/Korea) as fixed effects, and baseline value and placebo lead-in total IPSS change as fixed covariates.
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had non-missing data at baseline.
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description:
Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period.
Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
Overall Number of Participants Analyzed 301 305
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.1  (0.3) -2.7  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tadalafil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.060
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.2 to 0.0
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Tadalafil
Hide Arm/Group Description Placebo: 2 tablets [identical to 2.5-milligram (mg) tadalafil tablets] given orally once daily for 4 weeks, during the placebo lead-in period and for 12 weeks, during the double-blind treatment period. Tadalafil: 5 mg (two 2.5-mg tablets), given orally once daily for 12 weeks, during the double-blind treatment period. This followed a 4-week placebo lead-in period [2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily].
All-Cause Mortality
Placebo Tadalafil
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Tadalafil
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/304 (0.33%)      2/306 (0.65%)    
Cardiac disorders     
Cardio-respiratory arrest  1 [1]  1/304 (0.33%)  1 0/306 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Injury, poisoning and procedural complications     
Spinal cord injury cervical  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
[1]
Event resulted in death within 30 days of study drug discontinuation
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Tadalafil
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   75/304 (24.67%)      87/306 (28.43%)    
Blood and lymphatic system disorders     
Anaemia  1  0/304 (0.00%)  0 2/306 (0.65%)  2
Cardiac disorders     
Supraventricular extrasystoles  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Ear and labyrinth disorders     
Ear discomfort  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Vertigo  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Eye disorders     
Asthenopia  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Astigmatism  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Erythema of eyelid  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Eyelid oedema  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Vision blurred  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Vitreous detachment  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Vitreous floaters  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Gastrointestinal disorders     
Abdominal discomfort  1  1/304 (0.33%)  1 2/306 (0.65%)  3
Abdominal distension  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Abdominal pain lower  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Constipation  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Diarrhoea  1  1/304 (0.33%)  1 5/306 (1.63%)  5
Dry mouth  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Dyspepsia  1  2/304 (0.66%)  2 12/306 (3.92%)  12
Frequent bowel movements  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Gastric ulcer  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Gastritis  1  0/304 (0.00%)  0 2/306 (0.65%)  2
Gastritis atrophic  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Gastrointestinal motility disorder  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Gastrooesophageal reflux disease  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Gingivitis  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Lip dry  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Periodontal disease  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Periodontitis  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Stomatitis  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Vomiting  1  0/304 (0.00%)  0 2/306 (0.65%)  2
General disorders     
Granuloma  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Malaise  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Oedema peripheral  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Therapeutic response unexpected  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Hepatobiliary disorders     
Drug-induced liver injury  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Hepatic function abnormal  1  3/304 (0.99%)  3 1/306 (0.33%)  1
Infections and infestations     
Bronchitis  1  1/304 (0.33%)  1 1/306 (0.33%)  1
Fungal skin infection  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Gastroenteritis  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Herpes simplex  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Herpes zoster  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Influenza  1  1/304 (0.33%)  1 1/306 (0.33%)  1
Nasopharyngitis  1  10/304 (3.29%)  11 13/306 (4.25%)  14
Otitis media  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Pharyngitis  1  0/304 (0.00%)  0 3/306 (0.98%)  3
Tonsillitis  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Tracheitis  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Upper respiratory tract infection  1  5/304 (1.64%)  5 2/306 (0.65%)  2
Urinary tract infection  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Injury, poisoning and procedural complications     
Arthropod sting  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Hand fracture  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Joint dislocation  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Ligament sprain  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Muscle strain  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Upper limb fracture  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Investigations     
Alanine aminotransferase increased  1  4/304 (1.32%)  4 0/306 (0.00%)  0
Aspartate aminotransferase increased  1  6/304 (1.97%)  6 1/306 (0.33%)  1
Blood bilirubin increased  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Blood chloride decreased  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Blood creatine phosphokinase increased  1  7/304 (2.30%)  7 7/306 (2.29%)  7
Blood sodium decreased  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Blood urine  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Creatinine renal clearance decreased  1  1/304 (0.33%)  1 4/306 (1.31%)  4
Gamma-glutamyltransferase increased  1  3/304 (0.99%)  3 1/306 (0.33%)  1
Glucose urine present  1  0/304 (0.00%)  0 2/306 (0.65%)  2
White blood cell count decreased  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Metabolism and nutrition disorders     
Glucose tolerance impaired  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Hyperuricaemia  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/304 (0.33%)  1 2/306 (0.65%)  2
Arthropathy  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Back pain  1  3/304 (0.99%)  3 4/306 (1.31%)  4
Gouty arthritis  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Limb discomfort  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Musculoskeletal stiffness  1  1/304 (0.33%)  1 1/306 (0.33%)  1
Myalgia  1  1/304 (0.33%)  1 3/306 (0.98%)  3
Pain in extremity  1  1/304 (0.33%)  1 2/306 (0.65%)  2
Periarthritis  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Scoliosis  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Tenosynovitis  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Nervous system disorders     
Burning sensation  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Carotid arteriosclerosis  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Dizziness  1  0/304 (0.00%)  0 2/306 (0.65%)  2
Headache  1  6/304 (1.97%)  6 9/306 (2.94%)  9
Hypoaesthesia  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Psychiatric disorders     
Anxiety disorder  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Renal and urinary disorders     
Haematuria  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Proteinuria  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Renal impairment  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Urinary retention  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Reproductive system and breast disorders     
Erection increased  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Spontaneous penile erection  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Epistaxis  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Oropharyngeal discomfort  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Rhinitis allergic  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Rhinorrhoea  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Upper respiratory tract inflammation  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Skin and subcutaneous tissue disorders     
Dermatitis  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Dermatitis allergic  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Eczema  1  2/304 (0.66%)  2 4/306 (1.31%)  4
Photosensitivity reaction  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Pruritus  1  0/304 (0.00%)  0 1/306 (0.33%)  1
Urticaria  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Surgical and medical procedures     
Electrocauterisation  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Rectal polypectomy  1  1/304 (0.33%)  1 0/306 (0.00%)  0
Tooth extraction  1  2/304 (0.66%)  2 0/306 (0.00%)  0
Vascular disorders     
Hot flush  1  1/304 (0.33%)  1 2/306 (0.65%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01460342     History of Changes
Other Study ID Numbers: 14101
H6D-JE-LVJF ( Other Identifier: Eli Lilly and Company )
First Submitted: October 24, 2011
First Posted: October 26, 2011
Results First Submitted: July 23, 2013
Results First Posted: September 25, 2013
Last Update Posted: September 25, 2013