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Study of Tadalafil Once-a-Day for 12 Weeks in Japanese Men With Benign Prostatic Hyperplasia Followed by an Open-Label Extension

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00783094
First received: October 30, 2008
Last updated: March 18, 2011
Last verified: March 2011
History of Changes
Results First Received: June 25, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Benign Prostatic Hyperplasia
Interventions: Drug: Tadalafil 2.5 mg
Drug: Tadalafil 5 mg
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Tadalafil 2.5 mg 2.5 milligrams (mg) tadalafil tablet by mouth once a day for 12 weeks followed by 5 mg tadalafil tablet by mouth once a day for 42 weeks.
Tadalafil 5 mg 5 mg tadalafil tablet by mouth once a day for 12 weeks then continue 5 mg tadalafil tablet by mouth once a day for 42 weeks.
Placebo

Placebo tablet taken by mouth once a day for 12 weeks.

Then subjects may take 5 mg tadalafil tablet by mouth once a day for 42 weeks.

Participant Flow for 2 periods

 Period 1:   Randomized Double-Blind Treatment Period
    Tadalafil 2.5 mg     Tadalafil 5 mg     Placebo  
STARTED     142     140     140  
COMPLETED     135     128     131  
NOT COMPLETED     7     12     9  
Adverse Event                 4                 5                 5  
Lack of Efficacy                 0                 2                 1  
Physician Decision                 0                 2                 0  
Protocol Violation                 1                 2                 1  
Withdrawal by Subject                 2                 1                 2  

Period 2:   Open-Label Extension Period
    Tadalafil 2.5 mg     Tadalafil 5 mg     Placebo  
STARTED     135     128     131  
COMPLETED     113     109     101  
NOT COMPLETED     22     19     30  
Adverse Event                 12                 7                 16  
Death                 0                 0                 1  
Protocol Violation                 4                 5                 7  
Withdrawal by Subject                 1                 1                 3  
Physician Decision                 4                 2                 3  
Lack of Efficacy                 1                 4                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Tadalafil 2.5 mg 2.5 milligrams (mg) tadalafil tablet by mouth once a day for 12 weeks followed by 5 mg tadalafil tablet by mouth once a day for 42 weeks.
Tadalafil 5 mg 5 mg tadalafil tablet by mouth once a day for 12 weeks then continue 5 mg tadalafil tablet by mouth once a day for 42 weeks.
Placebo

Placebo tablet taken by mouth once a day for 12 weeks.

Then subjects may take 5 mg tadalafil tablet by mouth once a day for 42 weeks.
Total Total of all reporting groups

Baseline Measures
    Tadalafil 2.5 mg     Tadalafil 5 mg     Placebo     Total  
Number of Participants  
[units: participants]
 		  142     140     140     422  
Age  
[units: years]
Mean ± Standard Deviation 		  66.4  ± 7.4     66.9  ± 7.7     67.0  ± 6.9     66.8  ± 7.3  
Gender  
[units: participants]
 		       
Female     0     0     0     0  
Male     142     140     140     422  
Race/Ethnicity, Customized  
[units: participants]
 		       
Japanese     142     140     140     422  
Region of Enrollment  
[units: participants]
 		       
Japan     142     140     140     422  
Baseline (Visit 3) Benign Prostatic Hyperplasia Severity [1]
[units: participants]
 		       
Moderate     100     102     100     302  
Severe     42     38     40     120  
Current Alcohol Use  
[units: participants]
 		       
Yes     96     92     93     281  
No     46     48     47     141  
Current Tobacco Use  
[units: participants]
 		       
Yes     31     28     25     84  
No     61     72     70     203  
Unknown or Not Recorded     50     40     45     135  
Previous Alpha-blocker Use [2]
[units: participants]
 		       
Yes     111     108     106     325  
No     31     32     34     97  
Previous Benign Prostatic Hyperplasia Therapy [3]
[units: participants]
 		       
Yes     27     33     23     83  
No     115     107     117     339  
Previous Overactive Bladder Therapy [4]
[units: participants]
 		       
Yes     10     12     7     29  
No     132     128     133     393  
Body Mass Index [5]
[units: kilograms/meters squared]
Mean ± Standard Deviation 		  23.3  ± 2.4     23.5  ± 2.6     23.6  ± 2.9     23.5  ± 2.6  
Duration of BPH [6]
[units: years]
Mean ± Standard Deviation 		  4.1  ± 3.0     4.5  ± 3.3     4.1  ± 2.9     4.2  ± 3.1  
Height  
[units: centimeters]
Mean ± Standard Deviation 		  166.0  ± 5.9     166.9  ± 6.1     166.3  ± 6.3     166.4  ± 6.1  
Postvoid Residual Volume [7]
[units: mililiters]
Mean ± Standard Deviation 		  35.2  ± 46.6     32.2  ± 36.4     31.6  ± 42.7     33.0  ± 42.1  
Weight  
[units: kilograms]
Mean ± Standard Deviation 		  64.4  ± 8.6     65.4  ± 8.3     65.4  ± 10.2     65.1  ± 9.1  
[1] Participants with BPH were defined as having had signs and symptoms of benign prostatic hyperplasia (BPH) (as diagnosed by a qualified physician) >6 months at Visit 1. Signs and symptoms of BPH included those associated with voiding (obstructive symptoms, such as incomplete emptying, intermittency, weak stream, straining)and/or storage (irritative symptoms, such as frequency, urgency, or nocturia).
[2] Actual use of alpha-blockers within the previous 12 months.
[3] Actual benign prostatic hyperplasia (BPH) therapy within the previous 12 months.
[4] Actual overactive bladder (OAB) therapy within the previous 12 months.
[5] Body mass index (BMI) is an estimate of body fat based on body weight divided by height squared.
[6] Participants had signs and symptoms of benign prostatic hyperplasia (BPH) (as diagnosed by a qualified physician) >6 months at Visit 1.
[7] Postvoid residual volume (PVR) was measured by ultrasound at regular intervals.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 1

2.  Secondary:   Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 2

3.  Secondary:   Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 3

4.  Secondary:   Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint
Measure Description Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
Time Frame Baseline, 12 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set (FAS): participants who were randomized and started study medication.

Reporting Groups
  Description
Tadalafil 2.5 mg 2.5 milligrams (mg) tadalafil tablet by mouth once a day for 12 weeks followed by 5 mg tadalafil tablet by mouth once a day for 42 weeks.
Tadalafil 5 mg 5 mg tadalafil tablet by mouth once a day for 12 weeks then continue 5 mg tadalafil tablet by mouth once a day for 42 weeks.
Placebo

Placebo tablet taken by mouth once a day for 12 weeks.

Then subjects may take 5 mg tadalafil tablet by mouth once a day for 42 weeks.

Measured Values
    Tadalafil 2.5 mg     Tadalafil 5 mg     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  142     140     139  
Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint  
[units: units on a scale]
Least Squares Mean ± Standard Error 		  -0.5  ± 0.1     -0.7  ± 0.1     -0.4  ± 0.1  


Statistical Analysis 1 for Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint
Groups [1] Tadalafil 2.5 mg vs. Placebo
Method [2] ANCOVA
P Value [3] 0.249
Mean Difference (Final Values) [4] -0.2
Standard Error of the mean ± 0.1
95% Confidence Interval ( -0.4 to 0.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  With effects for treatment,BPH severity (moderate/severe), prior alpha blocker use (yes/no), and baseline value.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Least Squares Mean Difference = Tadalafil 2.5 mg - Placebo.

Statistical Analysis 2 for Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint
Groups [1] Tadalafil 5 mg vs. Placebo
Method [2] ANCOVA
P Value [3] 0.022
Mean Difference (Final Values) [4] -0.3
Standard Error of the mean ± 0.1
95% Confidence Interval ( -0.6 to -0.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  With effects for treatment,BPH severity (moderate/severe), prior alpha blocker use (yes/no) and baseline value.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Least Squares Mean Difference = Tadalafil 5 mg - Placebo.



5.  Secondary:   Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 5

6.  Secondary:   Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 6

7.  Secondary:   Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 7

8.  Secondary:   Number of Participants With Adverse Events During 12 Weeks of the Study   [ Time Frame: Baseline through 12 weeks ]
  Show Outcome Measure 8

9.  Secondary:   Change From Baseline in Blood Pressure at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 9

10.  Secondary:   Change From Baseline in Sitting Heart Rate at 12-Week Endpoint   [ Time Frame: Baseline, 12 Weeks ]
  Show Outcome Measure 10

11.  Secondary:   Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 11

12.  Secondary:   Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint   [ Time Frame: Baseline, 12 weeks ]
  Show Outcome Measure 12

13.  Secondary:   Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 13

14.  Secondary:   Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 14

15.  Secondary:   Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 15

16.  Secondary:   Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 16

17.  Secondary:   Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 17

18.  Secondary:   Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 18

19.  Secondary:   Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment   [ Time Frame: End of 12 weeks of double-blind through 54 weeks ]
  Show Outcome Measure 19

20.  Secondary:   Change From Baseline in Blood Pressure During at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 20

21.  Secondary:   Change From Baseline in Sitting Heart Rate at 54-Week Endpoint   [ Time Frame: Baseline, 54-weeks ]
  Show Outcome Measure 21

22.  Secondary:   Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 22

23.  Secondary:   Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint   [ Time Frame: Baseline, 54 weeks ]
  Show Outcome Measure 23


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00783094     History of Changes
Other Study ID Numbers: 12757, H6D-JE-LVIA
Study First Received: October 30, 2008
Results First Received: June 25, 2010
Last Updated: March 18, 2011
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency