Study of Tadalafil Once-a Day for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia

• ClinicalTrials.gov Identifier: NCT00384930
• Recruitment Status: Completed
• First Posted: October 6, 2006
• Results First Posted: August 19, 2009
• Last Update Posted: September 2, 2009
• Sponsor: Eli Lilly and Company
• Collaborator: ICOS Corporation
• Information provided by: Eli Lilly and Company

Tracking Information

• First Submitted Date: October 3, 2006
• First Posted Date: October 6, 2006
• Results First Submitted Date: October 17, 2008
• Results First Posted Date: August 19, 2009
• Last Update Posted Date: September 2, 2009
• Study Start Date: August 2006
• Actual Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 7, 2009)

• Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis [ Time Frame: Baseline and 12 weeks ]
  Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
• Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis [ Time Frame: Baseline and 12 weeks ]
  Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.

• Original Primary Outcome Measures (submitted: October 3, 2006): Tadalafil for 12 weeks is superior to placebo in improving the International Prostate Symptom Score (IPSS) in men with signs and symptoms of benign prostatic hyperplasia

Current Secondary Outcome Measures (submitted: July 7, 2009)

• Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore [ Time Frame: baseline and 12 weeks ]
  Measures irritative symptoms over the past 4 weeks of the IPSS. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 1 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15.
• Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore [ Time Frame: 12 weeks ]
  Measures obstructive symptoms over the past 4 weeks of the IPSS. IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 1 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20.
• Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) [ Time Frame: baseline and 12 weeks ]
  Measures nocturia (the need to get up at night to urinate) over the past 4 weeks. Scores range from 1 (few episodes of nocturia) to 5 (frequent episodes of nocturia).
• Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index [ Time Frame: baseline and 12 weeks ]
  Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
• Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) [ Time Frame: baseline and 12 weeks ]
  Measures the impact that symptoms of BPH has on the patients well being. This questionnaire has 4 questions assessing the level of urinary discomfort and it's impact on the patients. Three questions range from 0 (no impact) to 4 (high impact); one question ranges from 0 (low impact) to 4 (high impact). The BII score ranges from 0 to 16.
• Number of Participants Who Answer "Yes" to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) [ Time Frame: 12 weeks ]
  LUTS-GAQ Question asks the participant if the treatment they have been on has improved their uninary symptoms.
• Change From Baseline to 12 Week Endpoint in Peak Urinary Flow [ Time Frame: baseline and 12 weeks ]
  Measures the maximum flow rate of urine (measured in mL/s). This is a continuous parameter with positive numeric values.
• Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain [ Time Frame: baseline and 12 weeks ]
  Measures erectile function over the past 4 weeks on Questions 1-5 and 15 (6 questions) of the International Index of Erecile Function (IIEF) questionnaire. Scores range from 0 (low/no erectile function) to 5 (high erectile function), thus the 6 questions of the IIEF-EF domain range from 0 to 30.

• Original Secondary Outcome Measures (submitted: October 3, 2006): Tadalafil superior to placebo in improvement of selected IPSS subdomains and in uroflowmetry. Safety will also be assessed.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Tadalafil Once-a Day for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, 5-Group, Multinational Study to Evaluate the Efficacy, Dose Response, and Safety of Tadalafil Once-a-Day Dosing for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia
• Brief Summary: This is a randomized, double-blind, placebo-controlled, parallel-design, multinational, 12-week study to compare the efficacy, dose response, and safety of tadalafil once a day versus placebo in men with signs and symptoms of benign prostatic hyperplasia, including lower urinary tract symptoms.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Benign Prostatic Hyperplasia

Intervention

• Drug: tadalafil
  2.5 mg tadalafil tablet by mouth once a day for twelve weeks.
  Other Names:

  • LY450190
  • Cialis
  • IC351
• Drug: tadalafil
  5 mg tadalafil tablet by mouth once a day for twelve weeks.
  Other Names:

  • LY450190
  • Cialis
  • IC351
• Drug: tadalafil
  10 mg tadalafil tablet by mouth once a day for twelve weeks.
  Other Names:

  • LY450190
  • Cialis
  • IC351
• Drug: tadalafil
  20 mg tadalafil tablet by mouth once a day for twelve weeks.
  Other Names:

  • LY450190
  • Cialis
  • IC351
• Drug: placebo
  Placebo tablet taken by mouth one a day for twelve weeks

Study Arms

• Placebo Comparator: 1
  placebo tablet
  Intervention: Drug: placebo
• Active Comparator: 2
  2.5 mg tadalafil tablet
  Intervention: Drug: tadalafil
• Active Comparator: 3
  5 mg tadalafil tablet
  Intervention: Drug: tadalafil
• Active Comparator: 4
  10 mg tadalafil tablet
  Intervention: Drug: tadalafil
• Active Comparator: 5
  20 mg tadalafil tablet
  Intervention: Drug: tadalafil

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.
• Broderick GA, Brock GB, Roehrborn CG, Watts SD, Elion-Mboussa A, Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction. Urology. 2010 Jun;75(6):1452-8. doi: 10.1016/j.urology.2009.09.093. Epub 2010 Feb 16.
• Porst H, McVary KT, Montorsi F, Sutherland P, Elion-Mboussa A, Wolka AM, Viktrup L. Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia. Eur Urol. 2009 Oct;56(4):727-35. doi: 10.1016/j.eururo.2009.04.033. Epub 2009 Apr 22. Erratum In: Eur Urol. 2011 Jun;59(6):1082.
• Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol. 2008 Oct;180(4):1228-34. doi: 10.1016/j.juro.2008.06.079. Epub 2008 Aug 22.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 7, 2009): 1058
• Original Enrollment: Not Provided
• Actual Study Completion Date: October 2008
• Actual Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Males, 45 years or older, with benign prostatic hyperplasia, including lower urinary tract symptoms for at least 6 months prior to Visit 1 and an International Prostate Symptom Score (IPSS) greater than or equal to 13 at Visit 2.
• Agree not to use approved or experimental benign prostatic hyperplasia or erectile dysfunction treatments anytime during the study
• Have not taken finasteride or dutasteride therapy, any other lower urinary tract symptom (LUTS) therapy or phosphodiesterase type 5 (PDE5) inhibitors for specified duration of time prior to Visit 2.
• Have a prostate specific antigen (PSA) score within acceptable range defined for study or negative biopsy of the prostate for cancer within 12 months of Visit 1.

Exclusion Criteria:

• History of urinary retention or lower urinary tract (bladder) stones 6 months before the start of the study
• History of bladder outlet obstruction or urethral obstruction due to stricture, valves, sclerosis, or tumor.
• History of cardiac conditions including angina requiring certain treatment with nitrates, heart disease or coronary conditions including myocardial infarction, bypass surgery, angioplasty or stent placement for a specified time before starting the study.
• Certain neurological conditions associated with bladder problems or injuries to the brain or spinal cord within a specified time before starting the study.
• Nitrate use

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 45 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States
• Removed Location Countries: Australia, Canada, Mexico

Administrative Information

• NCT Number: NCT00384930
• Other Study ID Numbers: 9797; H6D-MC-LVHG
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Chief Medical Officer, Eli Lilly
• Original Responsible Party: Not Provided
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Lilly ICOS
• Collaborators: ICOS Corporation

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: August 2009