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

• Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
• Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).
• Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  Plasma from participants in the tadalafil treatment groups were assayed using a validated liquid chromatographic/mass spectrometric (LC/MS) method.
• Number of Participants With Adverse Events During 12 Weeks of the Study [ Time Frame: Baseline through 12 weeks ] [ Designated as safety issue: Yes ]
  A listing of Adverse Events are reported in the Reported Adverse Event Section.
• Change From Baseline in Blood Pressure at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Sitting Heart Rate at 12-Week Endpoint [ Time Frame: Baseline, 12 Weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
  Postvoid residual volume (PVR) is measured by ultrasound at regular intervals.
• Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
  Measurement of nanograms of PSA per milliliter (ng/mL) of blood.
• Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: No ]
  Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
• Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: No ]
  Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).
• 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 ] [ Designated as safety issue: Yes ]
  A listing of Adverse Events are reported in the Reported Adverse Event Section.
• Change From Baseline in Blood Pressure During at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Sitting Heart Rate at 54-Week Endpoint [ Time Frame: Baseline, 54-weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: Yes ]
  Measurement of nanograms of PSA per milliliter (ng/mL) of blood.
• Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint [ Time Frame: Baseline, 54 weeks ] [ Designated as safety issue: Yes ]
  Post residual volume (PVR) is measured by ultrasound at regular intervals.

• International Prostate Symptom Score (IPSS) storage sub score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• International Prostate Symptom Score (IPSS) Voiding sub score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Overactive Bladder Symptom Score (OABSS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Uroflowmetry parameter:peak flow rate (Qmax) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• International Prostate Symptom Score (IPSS) total score [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
• International Prostate Symptom Score (IPSS) storage sub score [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
• International Prostate Symptom Score (IPSS) Voiding sub score [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
• International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
• Overactive Bladder Symptom Score (OABSS) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
• Uroflowmetry parameter:peak flow rate (Qmax) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
• Adverse Events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Vital Signs [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Clinical Laboratory Tests [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Prostate Specific Antigen (PSA) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Postvoid Residual Volume (PVR) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Adverse Events [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
• Vital Signs [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
• Clinical Laboratory Tests [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
• Prostate Specific Antigen (PSA) [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
• Postvoid Residual Volume (PVR) [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
• tadalafil pharmacokinetics in Japanese men [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

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.

• Drug: Tadalafil 2.5 mg
  oral, daily
  Other Names:

  • LY450190
  • Cialis
• Drug: Tadalafil 5 mg
  oral, daily
  Other Names:

  • LY450190
  • Cialis
• Drug: Placebo
  oral, daily

• 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.
  Intervention: Drug: Tadalafil 2.5 mg
• 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.
  Intervention: Drug: Tadalafil 5 mg
• 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.

  Intervention: Drug: Placebo

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.