Clinical trial NCT02431754: A Study of Tadalafil (LY450190) in Participants With Lower Urinary Tract Symptoms (LUTS) Suggestive of Benign Prostatic Hyperplasia LUTS (BPH-LUTS).
Official title: A Post-Marketing Clinical Study of LY450190 (Combined With Alpha1 Blocker Treatment)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Benign Prostatic Hyperplasia
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Nippon Shinyaku Co., Ltd.
First posted: 2015-05-01
Enrollment: 171
Sex: MALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety and efficacy of the study drug known as tadalafil in participants with benign prostatic hyperplasia who are being treated with an alpha1 blocker. This study has two treatment periods. Participants will receive tadalafil or placebo in each treatment period.


Eligibility criteria: Inclusion Criteria:

* Present with benign prostatic hyperplasia (BPH; also referred to as BPH-LUTS), based on the disease diagnostic criteria, at study entry.
* Have been treated with a stable dose of an alpha1 blocker (tamsulosin 0.2 mg once daily or silodosin 4 mg twice daily) for at least 8 weeks prior to screening, and continue the same alpha1 blocker at the same dose for the entire duration of the study.
* Are Japanese men.
* Have prostate volume ≥20 milliliters (mL) estimated by transabdominal or transrectal ultrasound at screening.
* Have BPH-LUTS with a Total International Prostate Symptom Score (IPSS) of ≥12 at screening and baseline.
* Have moderate LUTS with urinary peak flow rate (Qmax) ≥4 to ≤15 mL/second at baseline, while meeting both of the following criteria:

  * Prevoid total bladder volume ≥150 to ≤550 mL as assessed by ultrasound
  * Minimum voided volume ≥125 mL
* Demonstrate ≥80% compliance with alpha1 blocker treatment\* during the screening period, documented at baseline

  * \*Tamsulosin: (Number of doses taken / Number of days to be treated) × 100
  * Silodosin: (Number of doses taken / Number of days to be treated) × 50

Exclusion Criteria:

* Prostate-specific antigen (PSA) \>10.0 nanograms (ng)/mL at screening.
* PSA ≥4.0 to ≤10.0 ng/mL at screening if prostate malignancy has not been ruled out to the satisfaction of a urologist.
* Bladder post-void residual (PVR) ≥150 mL by ultrasound determination at screening.
* History of any of the following pelvic conditions:

  * Pelvic surgery or any other pelvic procedure, including radical prostatectomy, pelvic surgery for removal of malignancy, or bowel resection
  * Pelvic radiotherapy
  * Any pelvic surgical procedure on the urinary tract, including minimally invasive BPH-LUTS therapies and penile implant surgery
  * Lower urinary tract malignancy or trauma
* Lower urinary tract instrumentation (including prostate biopsy) within 30 days of screening.
* History of urinary retention or lower urinary tract (bladder) stones within 6 months of screening.
* History of urethral obstruction due to stricture, valves, sclerosis, or tumor at screening.
* History of any of the following treatments within the indicated duration:

  * Antiandrogens within 11 months before screening
  * Dutasteride within 5 months before screening
  * Finasteride within 2 months before screening
  * Any erectile dysfunction treatment previously or currently
  * Any overactive bladder treatment within 4 weeks before screening
* Have a diagnosis or history of prostate cancer at screening.
* Current or history of malignancy at screening (except for treatment-free and relapse-free for ≥3 years at screening).
* Clinical evidence or history of any of the following bladder conditions:

  * Underactive Bladder
  * Detrusor-sphincter dyssynergia (contraction of the detrusor without sphincter relaxation)
  * Interstitial cystitis
* Clinical evidence of any of the following urinary tract conditions:

  * Active urogenital infection
  * Clinically significant microscopic hematuria as determined by a urologist
* History of significant renal insufficiency meeting either of the following:

  * Receiving renal dialysis
  * Creatinine clearance (CLcr) \<30 mL/minute
* Clinical evidence of severe hepatic impairment or Aspartate Transaminase (AST) or Alanine Transaminase (ALT) \>3 times the upper limit of normal range.
* History of any of the following cardiac conditions:

  * Current or history of angina requiring treatment with nitrates or nitric oxide donors
  * Current or history of unstable angina
  * Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention (e.g., coronary angioplasty)
* History of any of the following coronary conditions within 90 days of screening:

  * Myocardial infarction
  * Coronary artery bypass graft surgery
  * Percutaneous coronary intervention (for example, angioplasty or stent placement)
* Any evidence or history of heart failure (New York Heart Association \[NYHA\] ≥ Class III).
* Currently receiving alpha1 blocker therapy for the treatment of hypertension.
* Current or history of any of the following symptoms:

  * Symptoms associated with orthostasis (e.g., recurrent episodes of dizziness, lightheadedness, loss of consciousness, syncope)
  * Causeless fall within 1 year of screening
* Blood pressure-related findings of any of the following at screening:

  * Systolic blood pressure \>160 or \<90 millimeters of mercury (mm Hg)
  * Diastolic blood pressure \>100 or \<50 mm Hg
  * Malignant hypertension
  * Uncontrolled arrhythmia

Primary outcomes:
measure: Percentage of Participants Preferring Combination Therapy Over Alpha Blocker Alone on the Treatment Preference Questionnaire (TPQ)
timeFrame: Week 20
Secondary outcomes:
measure: Change From Baseline on the International Prostate Symptom Score (IPSS) Total Score
timeFrame: Baseline, Week 8
measure: Change From Baseline on the IPSS Storage (Irritative) Subscore
timeFrame: Baseline,Week 8
measure: Change From Baseline on the IPSS Voiding (Obstructive) Subscore
timeFrame: Baseline, Week 8
measure: Change From Baseline on the IPSS Quality of Life Score (IPSS QoL )
timeFrame: Baseline, Week 8
measure: Percentage of Participants With Global Impression of Improvement (PGI-I)
timeFrame: Week 8
measure: Percentage of Participants With PGI-I (Drug Attributes Questionnaire) on 8 Symptoms for BPH-Lower Urinary Tract Symptoms Improvement
timeFrame: Week 8
Other outcomes:
Locations:
city: Kyoto
country: Japan
facility: 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.
city: Maebashi
country: Japan
facility: 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.
city: Osaka
country: Japan
facility: 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.
city: Sagamihara
country: Japan
facility: 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.
city: Sakai
country: Japan
facility: 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.
city: Suita
country: Japan
facility: 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.
city: Takasaki
country: Japan
facility: 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.
city: Takatsuki
country: Japan
facility: 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.
city: Tokyo
country: Japan
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: