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

Lilly

Status and phase: Completed; Phase 3

Conditions: Benign Prostatic Hyperplasia

Treatments: Drug: Placebo; Drug: Tadalafil

Study type: Interventional

Funder types: Industry

Identifiers

NCT01460342

14101

H6D-JE-LVJF (Other Identifier)

Details and patient eligibility

About

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.

Full description

Tadalafil is being investigated as a treatment for men with signs and symptoms of benign prostatic hyperplasia [BPH; also referred to as urinary disturbance or BPH-LUTS (BPH-lower urinary tract symptoms)] in Japan and overseas. Overseas studies and the Japanese dose-finding study LVIA (NCT00783094) identified tadalafil 5 mg once-daily as the recommended dose. The long-term safety and maintenance of effect was confirmed in the open-label extension of study LVIA. The risk-benefit profile was further studied in the Asian study LVHB (NCT00861757).

This study, LVJF, is to confirm the efficacy and safety of tadalafil 5 mg once-daily in Asian men with BPH-LUTS.

Enrollment: 610 patients

Sex: Male

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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610 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Following the 4-week placebo lead-in period, this arm will consist of a 12-week placebo treatment period involving 2 x 2.5-milligram (mg) tadalafil placebo tablets taken orally once daily.

Treatment:

Drug: Placebo

Tadalafil

Experimental group

Description:

Following the 4-week placebo lead-in period, this arm will consist of a 12-week treatment period involving 2 x 2.5-mg tadalafil tablets taken orally once daily.

Treatment:

Drug: Tadalafil

Drug: Placebo