E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Effects on urodynamic parameters in men with benign prostatic hyperplasia (also referred to as BPH-LUTS [lower urinary tract symptoms]) with and without urodynamic evidence of bladder outlet obstruction. LUTS include urinary frequency, urgency, intermittency, nocturia, straining, incomplete emptying and weak urinary stream. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004446 |
E.1.2 | Term | Benign prostatic hyperplasia |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effect of tadalafil 20 mg once a day for 12 weeks on detrusor pressure at peak urinary flow rate versus placebo in men with signs and symptoms of benign prostatic hyperplasia, including lower urinary tract symptoms (BPH LUTS). |
|
E.2.2 | Secondary objectives of the trial |
To examine the effects of tadalafil 20 mg once a day for 12 weeks (compared with placebo) on the urodynamic parameters.
To assess the safety of tadalafil 20 mg once a day for 12 weeks in the treatment of men with BPH LUTS as examined by the following measures: - Adverse events - Clinical laboratory tests
To assess the efficacy of tadalafil 20 mg once a day for 12 weeks in the treatment of men with BPH LUTS as examined by the International Prostate Symptom Score (IPSS).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Present with BPH LUTS based on the disease diagnostic criteria at Visit 1. [2] Are men 45 years of age or older at Visit 1. [3] Provide signed informed consent document at Visit 1. [4] Agree not to use any other approved or experimental pharmacologic treatments for BPH LUTS, including alpha blockers, 5-alpha reductase inhibitors, PDE5 inhibitors, or herbal preparations at any time during the study. [5] Have not taken the following treatments within the indicated duration: [a] Finasteride or dutasteride therapy for at least 4 months prior to Visit 2. [b] All other LUTS therapy (including herbal preparations) for at least 4 weeks prior to Visit 2. [c] Any PDE5 inhibitor for at least 4 weeks prior to Visit 2. [6] Have LUTS with a total IPSS greater than or equal to 13 under 1 of the following conditions: [a] At Visit 1 if the subject does not require wash out of therapy for BPH LUTS. [b] At Visit 2 if the subject requires wash out (4 weeks) of BPH LUTS therapy.
|
|
E.4 | Principal exclusion criteria |
[1] PSA >10.0 ng/mL at Visit 1. [2] PSA of 4.0 to 10.0 ng/mL inclusive at Visit 1 without documentation of a histologic biopsy of the prostate negative for cancer within 12 months of Visit 1. [3] PVR measurement by ultrasound greater than or equal to 350 mL at Visit 1. [4] History of any of the following pelvic conditions: [a] Pelvic surgery or any other pelvic procedure, including radical prostatectomy, pelvic surgery for removal of malignancy, or bowel resection. [b] Pelvic radiotherapy. [c] Any pelvic surgical procedure on the urinary tract. [d] Lower urinary tract malignancy or trauma. [e] Chronic pelvic pain syndrome. [5] Lower urinary tract instrumentation within 30 days of Visit 1. [6] Any history of urinary retention or lower urinary tract stones within 6 months of Visit 1. [7] History of urethral obstruction due to stricture, valves, sclerosis, or tumor. [8] Clinical evidence or history of any of the following bladder conditions: [a] Bladder calculi. [b] Intravesical obstruction. [c] Atonic, decompensated, or hypocontractile bladder. [d] Detrusor-sphincter dyssynergia. [e] Interstitial cystitis. [9] Evidence of any of the following urinary tract conditions: [a] Urinary tract infection (UTI), defined as a positive urine culture at Visit 1, or a UTI that is not resolved at repeat testing following a course of antibiotic therapy. [b] Urinary tract inflammation at Visit 1, defined as a positive result for leukocyte esterase from a urine dipstick or >5 white blood cells (WBC) per high powered field on urinalysis from a centrifuged, clean-catch, midstream urine specimen. [c] Current antibiotic therapy for UTI at Visit 1. [10] Clinical evidence of prostate cancer. [11] Current neurologic disease or condition associated with neurogenic bladder. [12] History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance <50 mL/min at Visit 1 as calculated by the central laboratory using the Cockroft-Gault formula: (140 - age [years]) × weight [kg] / (72 × serum creatinine [mg/dL]) [13] Active symptomatic hepatobiliary disease at Visit 1. [14] History of any of the following cardiac conditions: [a] Angina requiring treatment with long-acting nitrates. [b] Angina requiring treatment with short-acting nitrates within 90 days of Visit 1. [c] Unstable angina within 90 days of Visit 1. [d] Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention. [15] History of any of the following coronary conditions within 90 days of Visit 1: [a] Myocardial infarction. [b] Coronary artery bypass graft surgery. [c] Percutaneous coronary intervention. [16] Evidence of heart disease categorized as NYHA above or including Class III within 6 months of Visit 1. [17] Systolic blood pressure >160 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at Visit 1 (if stress is suspected, retest under basal conditions), or malignant hypertension. [18] Scheduled or planned surgery (or any procedure requiring general, spinal, or epidural anesthesia) during the course of the study. [19] History of significant central nervous system (CNS) injuries within 6 months of Visit 1. [20] History of drug, alcohol, or substance abuse within 6 months of Visit 1. [21] Any condition that would interfere with subject ability to provide informed consent or comply with study instructions, would place subject at increased risk, or might confound the interpretation of the study results. [22] Current treatment with nitrates, cancer chemotherapy, androgens, anti androgens, estrogens, luteinizing hormone releasing hormone (LHRH) agonists/antagonists, or anabolic steroids. [23] Current systemic treatment with any of the following: [a] Potent cytochrome P450 3A4 (CYP3A4) inhibitors, such as ketoconazole or ritonavir. [b] Cytochrome P450 3A4 (CYP3A4) inducers, such as rifampicin or bosentan. [24] Glycosylated hemoglobin (HbA1c) >9% at Visit 1. [25] Invalid results from both the original and repeat baseline urodynamics assessments (as determined by the central reader). [26] Investigators, site personnel directly affiliated with this study, and their immediate families (defined as a spouse, parent, child, or sibling, whether biological or legally adopted). [27] Employed by Lilly or ICOS (that is, employees, temporary contract workers, or designees responsible for the conduct the study) and their immediate families. [28] Previously completed or withdrawn from this study or any other study investigating tadalafil. [29] Received treatment within the last 30 days with a drug or device that has not received regulatory approval for any indication at the time of Visit 1. [30] History of loss of vision in one eye due to NAION, regardless of whether this episode was in connection with previous PDE5 inhibitor exposure. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the detrusor pressure at maximum flow rate, which is measured during baseline and end of study urodynamics assessments. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 20 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 20 |