Overview

Phase 3 Study of Tadalafil Once-Daily in Asian Men With Benign Prostatic Hyperplasia (BPH)

Status:
Completed
Trial end date:
2012-10-01
Target enrollment:
0
Participant gender:
Male
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Eli Lilly and Company
Treatments:
Tadalafil
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.