Study to Treat Patients Who Have Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) With Tadalafil Daily

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multinational Study to Evaluate the Efficacy and Safety of Daily Tadalafil for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia

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.)

Study Overview

• Status: Completed
• Conditions: Benign Prostatic Hyperplasia
• Intervention / Treatment: Drug: tadalafil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1405
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Germany
  • Berlin, Germany, 13465
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Hamburg, Germany, 20354
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Marburg, Germany, 35039
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Muehlacker, Germany, D-75417
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Oranienburg, Germany, D-16515
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Italy
  • Bergamo, Italy, 24128
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Milan, Italy, 20132
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Napoli, Italy, 80131
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Orbassano, Italy, 10043
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Rome, Italy, 00161
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Mexico
  • Mexico City, Mexico, 10700
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Monterrey, Mexico, 64040
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Saltillo, Mexico, 25210
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Zapopan, Mexico, 45040
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Florida
    • Sarasota, Florida, United States, 34237
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Georgia
    • Roswell, Georgia, United States, 30076
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Illinois
    • Chicago, Illinois, United States, 60611
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • New York
    • Bayshore, New York, United States, 11706
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • New York, New York, United States, 10016
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Williamsville, New York, United States, 14221
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Ohio
    • Columbus, Ohio, United States, 43220
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men 45 years of age or older with Benign Prostatic Hyperplasia (BPH) also referred to as BPH-LUTS [lower urinary tract symptoms] based on the disease diagnostic criteria at the start of study.
• Provide signed informed consent at the start of the study.
• Have not taken Finasteride therapy for at least 3 months before study drug is dispensed and Dutasteride therapy for at least 6 months before study drug is dispensed.
• Have not taken other BPH therapy (including herbal preparations), overactive bladder (OAB) therapy, or erectile dysfunction (ED) therapy for at least 4 weeks prior to study drug is dispensed.
• Agree not to use any other approved or experimental pharmacologic BPH, OAB, or ED treatments anytime during the study
• Have LUTS with a Total International Prostate Symptom Score (IPSS) greater than or equal to 13 when study drug is dispensed.
• Have reduced peak urine flow rate when study drug is dispensed (measured by a special toilet equipment).
• Demonstrate compliance with study drug administration requirements.

Exclusion Criteria:

• Treated with nitrates for a cardiac conditions.
• Have unstable angina or angina that requires treatment.
• Have had any of the following in the past 90 days: Heart attack, also known as a myocardial infarction (MI); Heart bypass surgery (called coronary artery bypass graft surgery); Had a procedure to open up blood vessels in the heart known as angioplasty or stent placement (percutaneous coronary intervention).
• Have very high or very low blood pressure
• Have problems with kidneys, liver, or nervous system.
• Have uncontrolled diabetes.
• Have had a stroke or a significant injury to brain or spinal cord.
• Have prostate cancer, are being treated for cancer or have clinical evidence of prostate cancer (Prostate-Specific Antigen [PSA] greater than 10 nanograms/milliliter [ng/ml] at the start of study).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Following a 4-week placebo lead-in period, subjects received placebo tablet by mouth once daily over a 12-week period.
Experimental: Tadalafil	Drug: tadalafil; Following a 4-week placebo lead-in period, subjects received tadalafil 5 mg tablet by mouth once daily over a 12-week period.; Other Names: LY450190; Cialis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS)	The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index	The BPH Impact Index (BII) is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 4 weeks
Change From Baseline to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index	The BII is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore	IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore	IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question	Measures nocturia (the need to get up at night to urinate). Scores range from 0 (few episodes of nocturia) to 5 (frequent episodes of nocturia). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index	Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 12 weeks
Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories	A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).	12 weeks
Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories	Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse).	12 weeks
Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS)	The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 1 week
Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS)	The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 4 Weeks
Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores	Self-reported EF. Scores range from 0 (low or no EF) to 5 (high EF) on 6 questions (1-5, 15 of the IIEF). EF Domain scores range from 0 to 30. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry	Qmax was defined as the peak urine flow rate (measured in milliliters per second [mL/sec] using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 milliliters (mL) and the voided volume (Vcomp) was >=125 mL.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry	Qmean was defined as the mean urine flow rate (measured in mL/sec using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 mL and the Vcomp was >=125 mL.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry	Vcomp was defined as the volume of urine voided (measured in mL using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 mL and the Vcomp was >=125 mL.	Baseline, 12 weeks
Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume	The amount of urine remaining in the bladder after void completion.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Vlachopoulos C, Oelke M, Maggi M, Mulhall JP, Rosenberg MT, Brock GB, Esler A, Buttner H. Impact of cardiovascular risk factors and related comorbid conditions and medical therapy reported at baseline on the treatment response to tadalafil 5 mg once-daily in men with lower urinary tract symptoms associated with benign prostatic hyperplasia: an integrated analysis of four randomised, double-blind, placebo-controlled, clinical trials. Int J Clin Pract. 2015 Dec;69(12):1496-507. doi: 10.1111/ijcp.12722. Epub 2015 Aug 24.
• Porst H, Kim ED, Casabe AR, Mirone V, Secrest RJ, Xu L, Sundin DP, Viktrup L; LVHJ study team. Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an international randomized, double-blind, placebo-controlled trial. Eur Urol. 2011 Nov;60(5):1105-13. doi: 10.1016/j.eururo.2011.08.005. Epub 2011 Aug 12.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 20, 2009
• First Submitted That Met QC Criteria: January 20, 2009
• First Posted (Estimate): January 22, 2009

Study Record Updates

• Last Update Posted (Estimate): November 17, 2010
• Last Update Submitted That Met QC Criteria: October 19, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: Hyperplasia; Signs and Symptoms; Prostatic Diseases; Prostatic Hyperplasia; Genital Diseases, Male; BPH-LUTS
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: 10893 (Fred Hutch/University of Washington Cancer Consortium); H6D-MC-LVHJ (Other Identifier: Eli Lilly and Company)