A Study of Tadalafil in Men With Benign Prostatic Hyperplasia - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by (Responsible Party):	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00970632

Purpose

The purpose of this study is to determine whether an experimental drug known as tadalafil given once daily can reduce the symptoms associated with Benign Prostatic Hyperplasia (straining, urinary frequency, feeling like your bladder is still full etc.)

Condition	Intervention	Phase
Benign Prostatic Hyperplasia (BPH)	Drug: Tadalafil 5 mg Drug: Placebo tablet Drug: Tamsulosin Drug: Placebo capsule	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Global Multicenter Study to Evaluate the Efficacy and Safety of Tadalafil Once Daily Dosing for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia

Resource links provided by NLM:

MedlinePlus related topics: Urine and Urination

Drug Information available for: Tamsulosin Tamsulosin hydrochloride Tadalafil

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.

Secondary Outcome Measures:

Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
IPSS storage (irritative) subscore was the sum of Component Questions 2, 4 and 7 of the IPSS questionnaire. Scores ranged from 0 (no irritative symptoms) to 5 (frequent irritative symptoms); therefore, the 3 questions of the irritative subscore ranged from 0 to 15. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks. [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
IPSS voiding (obstructive) subscore was the sum of Component Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores ranged from 0 (no obstructive symptoms)-5 (frequent obstructive symptoms); therefore, the 4 questions of the obstructive score ranged from 0-20. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
The IPSS nocturia question (Component Question 7) measured nocturia (need to urinate at night) over the past 4 weeks. Scores ranged from 0 (no episodes of nocturia)-5 (5 or more episodes of nocturia). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
IPSS QoL assessed QoL by urinary symptoms, with scores ranging from 0 (delighted)-6 (terrible). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week [ Time Frame: Baseline, 1 week ] [ Designated as safety issue: No ]
The mIPSS Total Score covered a time period of 1 week and was obtained by combining scores of responses to Component Questions 1-7. Each question was scored from 0-5 for an mIPSS range of 0-35 points; higher numerical scores represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 1 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Patient Global Impression of Improvement (PGI-I) at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The PGI-I was a participant-rated instrument that measured the improvement or worsening of the participant's symptoms based on a 7-point scale at Week 12. A score of 1=participant felt symptoms were "very much better"; score of 2=participant felt symptoms were "much better"; score of 3=participant felt symptoms were "a little better"; score of 4=participant felt "no change" in symptoms; score of 5=participant felt symptoms were "a little worse"; score of 6=participant felt symptoms were "much worse"; score of 7=participant felt symptoms were "very much worse".
Clinician Global Impression of Improvement (CGI-I) at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The CGI-I was an investigator-rated instrument that measured improvement or worsening of the participant's symptoms based on a 7-point scale. A score of 1=participant felt symptoms were "very much better"; score of 2=participant felt symptoms were "much better"; score of 3=participant felt symptoms were "a little better"; score of 4=participant felt "no change" in symptoms; score of 5=participant felt symptoms were "a little worse"; score of 6=participant felt symptoms were "much worse"; score of 7=participant felt symptoms were "very much worse".
Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 12 Weeks: Overall [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The TSS-BPH was a validated participant-rated instrument that measured participant satisfaction with treatment based on a 13-item questionnaire. The overall TSS-BPH score was converted to a percentage of the maximum value possible (percent ranged from 0-100) with lower scores indicating greater satisfaction.
Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
IIEF measured self-reported EF over the past 4 weeks. Scores ranged from 0 (low or no EF)-5 (high EF) on 6 questions (1-5, 15 of the IIEF). Total EF Domain scores ranged from 1-30. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Change From Baseline in Peak Urine Flow Rate (Q-Max) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Q-max (peak urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was ≥125 mL.
Change From Baseline in Mean Urine Flow Rate (Q-Mean) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Q-mean (mean urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was >=125 mL.
Change From Baseline in Volume of Voided Urine (V-Comp) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
V-comp (volume of urine voided) was measured in milliliters (mL) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and V-comp was ≥125 mL.
Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
PVR was the amount of urine remaining in the bladder after void completion.

Enrollment:	511
Study Start Date:	October 2009
Study Completion Date:	January 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Placebo tablet with tamsulosin dose orally (po) once daily (QD) and placebo capsule with tadalafil dose po QD for 12 weeks	Drug: Placebo tablet Placebo tablet po QD for 12 weeks Drug: Placebo capsule Placebo capsule po QD for 12 weeks
Experimental: Tadalafil 5 milligram (mg) Tadalafil 5 mg tablet po QD and placebo capsule po QD for 12 weeks	Drug: Tadalafil 5 mg Tadalafil 5 mg po QD for 12 weeks Other Names: Cialis LY450190
Active Comparator: Tamsulosin 0.4 mg Tamsulosin 0.4 mg capsule po QD and placebo tablet po QD for 12 weeks	Drug: Tamsulosin Tamsulosin 0.4 mg po QD for 12 weeks

Ages Eligible for Study:	45 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00970632 History of Changes
Other Study ID Numbers:	12932, H6D-MC-LVID
Study First Received:	September 1, 2009
Results First Received:	November 21, 2011
Last Updated:	March 8, 2012
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Austria: Federal Office for Safety in Health Care Belgium: Federal Agency for Medicinal Products and Health Products France: Afssaps - French Health Products Safety Agency Germany: Federal Institute for Drugs and Medical Devices Greece: Ethics Committee Greece: National Organization of Medicines Italy: Ministry of Health Mexico: Federal Commission for Sanitary Risks Protection Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Ethics Committee Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products