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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Study to Evaluate the Efficacy and Safety of Tadalafil Once-a-day Dosing for 12 Weeks in Asian Men With Signs and Symptoms of

Brief Summary: This is a phase 3, randomized, double-blind, placebo-controlled, parallel-design, multinational study to evaluate the efficacy and safety of tadalafil once-a-day dosing for 12 weeks in Asian men with signs and symptoms of benign prostatic hyperplasia.

Detailed Summary:

Tadalafil is being investigated as a treatment for men with signs and symptoms of benign prostatic hyperplasia [BPH; also referred to as urinary disturbance or BPH-LUTS (BPH-lower urinary tract symptoms)] in Japan and overseas. Overseas studies and the Japanese dose-finding study LVIA (NCT00783094) identified tadalafil 5 mg once-daily as the recommended dose. The long-term safety and maintenance of effect was confirmed in the open-label extension of study LVIA. The risk-benefit profile was further studied in the Asian study LVHB (NCT00861757).

This study, LVJF, is to confirm the efficacy and safety of tadalafil 5 mg once-daily in Asian men with BPH-LUTS.

Current Primary Outcome: Change From Baseline in Total Score of International Prostate Symptom Score (IPSS) at 12 Weeks [ Time Frame: Baseline, 12 weeks ]

Original Primary Outcome: Change From Baseline in Total Score of International Prostate Symptom Score (IPSS) at 12 Weeks [ Time Frame: Baseline, 12 weeks ]

Current Secondary Outcome:

• Change From Baseline in Total Score of International Prostate Symptom Score (IPSS) [ Time Frame: Baseline, 4 weeks, 8 weeks ]
  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.
• Change From Baseline in the International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks ]
  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.
• Change From Baseline in the International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks ]
  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.
• Change From Baseline in the International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks ]
  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.
• Patient Global Impression of Improvement (PGI-I) Scale at 12 Weeks [ Time Frame: 12 Weeks ]
  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).
• Clinician Global Impression of Improvement (CGI-I) Scale at 12 Weeks [ Time Frame: 12 Weeks ]
  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).
• Change From Baseline in Modified International Prostate Symptom Score (mIPSS) Score at 2 Weeks [ Time Frame: Baseline, 2 weeks ]
  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.

Original Secondary Outcome:

• Change from Baseline in the IPSS storage (Irritative) Subscore [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks ]
• Change from Baseline in the IPSS voiding (Obstructive) subscore [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks ]
• Change from Baseline in the IPSS Quality of Life (QoL) Index [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks ]
• Patient Global Impression of Improvement (PGI-I) Scale at 12 Weeks [ Time Frame: 12 Weeks ]
• Clinician Global Impression of Improvement (CGI-I) Scale at 12 Weeks [ Time Frame: 12 Weeks ]
• Change from Baseline in modified IPSS score at 2 Weeks [ Time Frame: Baseline, 2 weeks ]
• Change From Baseline in Total Score of International Prostate Symptom Score (IPSS) [ Time Frame: Baseline, 4 weeks, 8 weeks ]

Dates:
Date Received: October 24, 2011
Date Started: December 2011
Date Completion:
Last Updated: July 23, 2013
Last Verified: July 2013