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

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00783094
First received: October 30, 2008
Last updated: March 18, 2011
Last verified: March 2011
  Purpose

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 Intervention Phase
Benign Prostatic Hyperplasia
Drug: Tadalafil 2.5 mg
Drug: Tadalafil 5 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint [ Time Frame: Baseline, 12 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 422
Study Start Date: November 2008
Study Completion Date: April 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00783094

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

No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00783094     History of Changes
Other Study ID Numbers: 12757, H6D-JE-LVIA
Study First Received: October 30, 2008
Results First Received: June 25, 2010
Last Updated: March 18, 2011
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Prostatic Hyperplasia
Hyperplasia
Prostatic Diseases
Genital Diseases, Male
Pathologic Processes
Tadalafil
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014