Phase 3 Study of Tadalafil Once-Daily in Asian Men With Benign Prostatic Hyperplasia (BPH)
Condition: Benign Prostatic Hyperplasia
MeSH terms: Prostatic Hyperplasia; Hyperplasia
Intervention: Tadalafil; Placebo
Intervention description: 5 mg (2 x 2.5-mg tablets), given once daily as oral tablet; 2 tablets (identical to 2.5-mg tadalafil tablets) given orally once daily.
Intervention MeSH terms: Tadalafil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 610.0
Sex: Male
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Prostatic hyperplasia; Benign prostatic hyperplasia; Lower urinary tract

Summary:

      This is a phase 3, randomized, double-blind, placebo-controlled, parallel-design,
      multinational study to evaluate the efficacy and safety of tadalafil once-a-day dosing for 12
      weeks in Asian men with signs and symptoms of benign prostatic hyperplasia.
    

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.

          -  Provide signed informed consent at study entry.

          -  Have BPH-LUTS with a Total International Prostate Symptom Score (IPSS) of ≥13 at
             beginning of placebo lead-in period.

          -  Have bladder outlet obstruction of intermediate severity as defined by a urinary peak
             flow rate (Qmax) of ≥4 to ≤15 milliliters per second (mL/sec) [from a prevoid total
             bladder volume (assessed by ultrasound) of ≥150 to ≤550 milliliters (mL) and a minimum
             voided volume of 125 mL] at beginning of placebo lead-in period.

          -  Have prostate volume ≥20 mL estimated by transabdominal or transrectal ultrasound at
             study entry.

          -  Agree not to use any other approved or experimental pharmacologic BPH, erectile
             dysfunction (ED) and/or overactive bladder (OAB) treatments, including alpha-blockers,
             5-alpha reductase inhibitors (5-ARIs), phosphodiesterase type 5 (PDE5) inhibitors, or
             herbal preparations at any time during the study.

          -  Have not taken the following treatments within the indicated duration:

               -  Finasteride therapy for at least 3 months prior to beginning of placebo lead-in
                  period.

               -  Dutasteride therapy for at least 6 months prior to beginning of placebo lead-in
                  period.

               -  Anti-androgenic hormone therapy at least 12 months prior to beginning of placebo
                  lead-in period.

               -  All other BPH therapy (including herbal preparations) for at least 4 weeks prior
                  to beginning of placebo lead-in period.

               -  ED therapy for at least 4 weeks prior to beginning of placebo lead-in period.

               -  OAB therapy for at least 4 weeks prior to beginning of placebo lead-in period.

          -  Demonstrate compliance with study drug administration requirements during the placebo
             lead-in period by administering ≥70% of prescribed doses, confirmed by documentation
             that the participant returned ≤30% of prescribed doses at randomization.

        Exclusion Criteria:

          -  Prostate-specific antigen (PSA) >10.0 nanograms per milliliter (ng/mL) at study entry.

          -  PSA ≥4.0 to ≤10.0 ng/mL at study entry, if prostate malignancy has not been ruled out
             to the satisfaction of an urologist.

          -  Bladder postvoid residual (PVR) ≥300 mL by ultrasound determination at study entry.

          -  History of any of the following pelvic conditions (checked at study entry):

               -  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 day of study
             entry.

          -  History of urinary retention or lower urinary tract (bladder) stones within 6 months
             of study entry.

          -  History of urethral obstruction due to stricture, valves, sclerosis, or tumor.

          -  Current neurologic disease or condition associated with neurogenic bladder (for
             example, Parkinson's disease, multiple sclerosis) at study entry.

          -  Clinical evidence of prostate cancer.

          -  Clinical evidence of any of the following bladder conditions:

               -  Mullerian duct cysts.

               -  Atonic, decompensated, or hypocontractile bladder.

               -  Detrusor-sphincter dyssynergia (contraction of the detrusor without sphincter
                  relaxation).

               -  Intravesical obstruction (for example, intravesical median lobe of the prostate).

               -  Interstitial cystitis.

          -  Clinical evidence of any of the following urinary tract conditions at study entry:

               -  Urinary tract infection.

               -  Urinary tract inflammation (including prostatitis). Urinary tract
                  infection/inflammation is defined as a positive result for leukocyte esterase
                  from a urine dipstick or >5 white blood cells (WBCs) per high-powered field on
                  urinalysis from a centrifuged, clean-catch, midstream urine specimen.

               -  Current antibiotic therapy for urinary tract infection.

               -  Clinically significant microscopic hematuria as determined by an urologist.

          -  History of significant renal insufficiency, defined as receiving renal dialysis or
             having an estimated creatinine clearance <30 milliliters per minute (mL/min) at study
             entry, as calculated by the central laboratory using the Cockcroft-Gault formula.

          -  Clinical evidence of severe hepatic impairment [aspartate transaminase (AST) or
             alanine transaminase (ALT) >3-fold of the upper limit of normal range] at study entry.

          -  History of any of the following cardiac conditions (checked at study entry):

               -  Angina requiring treatment with long-acting nitrates.

               -  Angina requiring treatment with short-acting nitrates within 90 days of study
                  entry.

               -  Unstable angina within 90 days of study entry.

               -  Positive cardiac stress test without documented evidence of subsequent, effective
                  cardiac intervention.

          -  History of any of the following coronary conditions within 90 days of study entry:

               -  Myocardial infarction.

               -  Coronary artery bypass graft surgery.

               -  Percutaneous coronary intervention (for example, angioplasty or stent placement).

          -  Any evidence of heart disease [New York Heart Association (NYHA) ≥Class III] within 6
             months of study entry.

          -  Systolic blood pressure >160 or <90 millimeters of mercury (mm Hg) or diastolic blood
             pressure >100 or <50 mm Hg at study entry (if stress is suspected, retest under basal
             conditions), or malignant hypertension.

          -  Glycosylated hemoglobin (HbA1c) >9% at study entry.

          -  Scheduled or planned surgery (or any procedure requiring general, spinal, or epidural
             anesthesia) during the course of the study.

          -  History of significant central nervous system injuries (including stroke or spinal
             cord injury) within 6 months of study entry.

          -  History of drug, alcohol, or substance abuse within 6 months of study entry.

          -  Current treatment with nitrates, androgens, antiandrogens, estrogens, luteinizing
             hormone-releasing hormone agonists/antagonists, or anabolic steroids at study entry.

          -  Current systemic treatment with any of the following:

               -  Potent cytochrome P450 3A4 (CYP3A4) inhibitors, such as ketoconazole or
                  ritonavir.

               -  CYP3A4 inducers such as rifampicin.

          -  Known or suspected to be hypersensitive to tadalafil, or any study drug components.

          -  Any conditions that would interfere with a participant's ability to provide informed
             consent or comply with study instructions, would place participant at increased risk,
             or might confound the interpretation of the study results.

          -  Previously completed or withdrawn from this study or any other study investigating
             tadalafil.

          -  Received treatment within the last 30 days with a drug or device that has not received
             regulatory approval for any indications at the time of informed consent. Participants
             who have been screen failures in previous studies may be eligible.