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

• ClinicalTrials.gov Identifier: NCT00783094
• Recruitment Status: Completed
• First Posted: October 31, 2008
• Results First Posted: July 28, 2010
• Last Update Posted: March 29, 2011
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Benign Prostatic Hyperplasia	Drug: Tadalafil 2.5 mg; Drug: Tadalafil 5 mg; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 422 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2008
• Actual Primary Completion Date: June 2009
• Actual Study Completion Date: April 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
   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.

Secondary Outcome Measures :

1. Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
   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.
2. Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
   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.
3. Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
   Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
4. Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
   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.
5. Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
   Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).
6. Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement [ Time Frame: Baseline, 12 weeks ]
   Plasma from participants in the tadalafil treatment groups were assayed using a validated liquid chromatographic/mass spectrometric (LC/MS) method.
7. Number of Participants With Adverse Events During 12 Weeks of the Study [ Time Frame: Baseline through 12 weeks ]
   A listing of Adverse Events are reported in the Reported Adverse Event Section.
8. Change From Baseline in Blood Pressure at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
9. Change From Baseline in Sitting Heart Rate at 12-Week Endpoint [ Time Frame: Baseline, 12 Weeks ]
10. Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
    Postvoid residual volume (PVR) is measured by ultrasound at regular intervals.
11. Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ]
    Measurement of nanograms of PSA per milliliter (ng/mL) of blood.
12. Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    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.
13. Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    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.
14. Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    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.
15. Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
16. Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    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.
17. Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).
18. Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment [ Time Frame: End of 12 weeks of double-blind through 54 weeks ]
    A listing of Adverse Events are reported in the Reported Adverse Event Section.
19. Change From Baseline in Blood Pressure During at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
20. Change From Baseline in Sitting Heart Rate at 54-Week Endpoint [ Time Frame: Baseline, 54-weeks ]
21. Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    Measurement of nanograms of PSA per milliliter (ng/mL) of blood.
22. Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ]
    Post residual volume (PVR) is measured by ultrasound at regular intervals.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Japan

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.

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

Sponsors and Collaborators

Eli Lilly and Company

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

More Information

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00783094
• Other Study ID Numbers: 12757; H6D-JE-LVIA ( Other Identifier: Eli Lilly and Company )
• First Posted: October 31, 2008
• Results First Posted: July 28, 2010
• Last Update Posted: March 29, 2011
• Last Verified: March 2011

Additional relevant MeSH terms:

Prostatic Hyperplasia; Hyperplasia; Pathologic Processes; Prostatic Diseases; Tadalafil; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents