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

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:

Drug Information available for: Tadalafil

U.S. FDA Resources

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 June 18, 2013