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

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Study to Evaluate the Efficacy and Safety of Tadalafil Once-a-Day Dosing for 12 Weeks Followed by an Open-Label Extension to Evaluate the Long-Term Safety and Efficacy of Tadalafil in Japanese Men With Signs and Symptoms of Benign Prostatic Hyperplasia

This study is a randomized, double-blind, placebo-controlled, parallel-design to compare the efficacy and safety of tadalafil once-a-day dosing versus placebo for 12 weeks followed by an open-label extension to evaluate the long-term safety and efficacy of tadalafil in Japanese men with signs and symptoms of benign prostatic hyperplasia.

Study Overview

• Status: Completed
• Conditions: Benign Prostatic Hyperplasia
• Intervention / Treatment: Drug: Placebo; Drug: Tadalafil 2.5 mg; Drug: Tadalafil 5 mg

• Study Type: Interventional
• Enrollment (Actual): 422
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 274-0825
    • 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.
  • Hiroshima, Japan, 730-0013
    • 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.
  • Kanagawa, Japan, 226-0025
    • 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.
  • Kyoto, Japan, 607-8085
    • 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.
  • Osaka, Japan, 561-0832
    • 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.
  • Tokyo, Japan, 150-0002
    • 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:

• Japanese Males, 45 years old or older, with benign prostatic hyperplasia (BPH) 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 any other approved or experimental pharmacologic BPH, erectile dysfunction (ED), and/or overactive bladder (OAB) treatments at any time during the study.
• Have not taken Finasteride or Dutasteride therapy, Anti-androgenic hormone or any other BPH therapy, ED or OAB therapy for specified duration of time prior to Visit 2.

Exclusion Criteria:

• Prostate specific antigen (PSA) score beyond acceptable range defined for study at Visit 1.
• History of urinary retention or lower urinary tract (bladder) stones within 6 months of Visit 1.
• History of urethral obstruction due to stricture, valves, sclerosis, or tumor at Visit 1.
• Clinical evidence of prostate cancer at Visit 1.
• Clinical evidence of any of the bladder or urinary tract conditions, which may affect lower urinary tract symptom at Visit 1.
• History of cardiac conditions, including Angina requiring certain treatment with nitrates, unstable angina defined for study, positive cardiac stress test before starting the study.
• History of significant central nervous system (CNS) injuries (including stroke or spinal cord injury) within 6 months of Visit 1.
• Use of any nitrates, cancer chemotherapy, androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone (LHRH) agonists/antagonists, or anabolic steroids at Visit 1.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tadalafil 2.5 milligrams (mg); 2.5 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.	Drug: Tadalafil 2.5 mg; oral, daily; Other Names: LY450190; Cialis
Experimental: 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.	Drug: Tadalafil 5 mg; oral, daily; Other Names: LY450190; Cialis
Placebo Comparator: 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.	Drug: Placebo; oral, daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint	The IPSS Total Score is obtained by combining the scores of the responses to 1 through 7 component questions. Each question is scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint	IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15.	Baseline, 12 weeks
Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint	IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20.	Baseline, 12 weeks
Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint	Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).	Baseline, 12 weeks
Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint	The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms.	Baseline, 12 weeks
Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint	Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).	Baseline, 12 weeks
Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement	Plasma from participants in the tadalafil treatment groups were assayed using a validated liquid chromatographic/mass spectrometric (LC/MS) method.	Baseline, 12 weeks
Number of Participants With Adverse Events During 12 Weeks of the Study	A listing of Adverse Events are reported in the Reported Adverse Event Section.	Baseline through 12 weeks
Change From Baseline in Blood Pressure at 12-Week Endpoint		Baseline, 12 weeks
Change From Baseline in Sitting Heart Rate at 12-Week Endpoint		Baseline, 12 Weeks
Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint	Postvoid residual volume (PVR) is measured by ultrasound at regular intervals.	Baseline, 12 weeks
Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint	Measurement of nanograms of PSA per milliliter (ng/mL) of blood.	Baseline, 12 weeks
Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint	The IPSS Total Score is obtained by combining the scores of the responses to 1 through 7 component questions. Each question is scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms.	Baseline, 54 weeks
Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint	IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15.	Baseline, 54 weeks
Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint	IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20.	Baseline, 54 weeks
Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint	Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).	Baseline, 54 weeks
Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint	The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms.	Baseline, 54 weeks
Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint	Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).	Baseline, 54 weeks
Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment	A listing of Adverse Events are reported in the Reported Adverse Event Section.	End of 12 weeks of double-blind through 54 weeks
Change From Baseline in Blood Pressure During at 54-Week Endpoint		Baseline, 54 weeks
Change From Baseline in Sitting Heart Rate at 54-Week Endpoint		Baseline, 54-weeks
Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint	Measurement of nanograms of PSA per milliliter (ng/mL) of blood.	Baseline, 54 weeks
Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint	Post residual volume (PVR) is measured by ultrasound at regular intervals.	Baseline, 54 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: October 30, 2008
• First Submitted That Met QC Criteria: October 30, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Estimate): March 29, 2011
• Last Update Submitted That Met QC Criteria: March 18, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• 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: 12757; H6D-JE-LVIA (Other Identifier: Eli Lilly and Company)