E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Benign Prostatic Hyperplasia (BPH) |
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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 |
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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 evaluate the efficacy of tadalafil 5 mg daily for 12 weeks compared with placebo in improving the International Prostate Symptom Score (IPSS) in men with signs and symptoms of benign prostatic hyperplasia (BPH; also referred to as BPH-LUTS [lower urinary tract symptoms]). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the change from baseline of tadalafil 5 mg daily for 12 weeks compared with placebo in the treatment of men with BPH-LUTS as assessed by BPH Impact Index (BII), IPSS domains and Global Impression of Improvement indices
To evaluate the change from baseline of tadalafil 5 mg daily for 12 weeks compared with placebo in the treatment of men with BPH-LUTS as assessed by uroflowmetry measurements
To evaluate the change from baseline of tadalafil 5 mg daily compared with placebo after 1 week of treatment in men with BPH-LUTS as assessed by the Modified IPSS
To evaluate the change from baseline of tadalafil 5 mg compared with placebo after 4 weeks of treatment in men with BPH-LUTS
To examine the impact of tadalafil 5 mg for 12 weeks on erectile function (EF) in men with both BPH-LUTS and erectile dysfunction as assessed by the International Index of Erectile Function EF Domain
To assess the safety of tadalafil 5 mg for 12 weeks in the treatment of men with BPH-LUTS |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Present with benign prostatic hyperplasia based on the disease diagnostic criteria (Section 4.1.1 of protocol) at Visit 1. [2] Are men 45 years of age or older at Visit 1. [3] Provide signed informed consent at Visit 1. [4] Agree not to use any other approved or experimental pharmacologic BPH, overactive bladder (OAB), or erectile dysfunction (ED) treatments, including alpha blockers, 5-alpha reductase inhibitors (5 ARIs), antimuscarinics, phosphodiesterase type 5 (PDE5) inhibitors, or herbal preparations at any time during the study. [5] Have not taken the following treatments within the indicated duration: [a] Finasteride therapy for at least 3 months prior to Visit 2. [b] Dutasteride therapy for at least 6 months prior to Visit 2. [c] All other BPH therapy (including herbal preparations) for at least 4 weeks prior to Visit 2. [d] OAB therapy for at least 4 weeks prior to Visit 2. [e] ED therapy for at least 4 weeks prior to Visit 2. [6] Have LUTS with a Total International Prostate Symptom Score (IPSS) greater than or equal to 13 at Visit 2. [7] Have bladder outlet obstruction as defined by a urinary peak flow rate (Qmax) of greater than or equal to 4 to less than or equal to 15 mL/second (from a prevoid total bladder volume [assessed by ultrasound] of greater than or equal to 150 to less than or equal to 550 mL and a minimum voided volume of 125 mL) at Visit 2. [8] Demonstrate compliance with study drug administration requirements during the placebo lead-in period by administering greater than or equal to 70% of prescribed doses, confirmed by documentation that the subject returned less than or equal to 30% of prescribed doses at Visit 3.
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E.4 | Principal exclusion criteria |
[9] Prostate specific antigen (PSA) > 10.0 ng/mL at Visit 1. [10] PSA greater than or equal to 4.0 to less than or equal to 10.0 ng/mL at Visit 1 if prostate malignancy has not been ruled out to the satisfaction of an urologist. [11] Bladder postvoid residual volume (PVR) greater than or equal to 300 mL by ultrasound determination at Visit 1. [12] History of any of the following pelvic conditions: [a] Pelvic surgery or any other pelvic procedure. [b] Pelvic radiotherapy. [c] Any pelvic surgical procedure of the urinary tract. [d] Lower urinary tract malignancy or trauma. [13] Lower urinary tract instrumentation within 30 days of Visit 1. [14] History of urinary retention or lower urinary tract stones within 6 months of Visit 1. [15] History of urethral obstruction due to stricture, valves, sclerosis, or tumor. [16] Clinical evidence of any of the following bladder conditions: [a] Mullerian duct cysts. [b] Atonic, decompensated, or hypocontractile bladder. [c] Detrusor-sphincter dyssynergia. [d] Intravesical obstruction. [e] Interstitial cystitis. [17] Clinical evidence of any of the following urinary tract conditions at Visit 1: [a] Urinary tract infection. [b] Urinary tract inflammation. [c] Current antibiotic therapy for urinary tract infection. [d] Clinically significant microscopic haematuria. [18] Clinical evidence of prostate cancer. [19] Current neurologic disease or condition associated with neurogenic bladder. [20] History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance < 30 mL/minute at Visit 1. [21] Clinical evidence of severe hepatic impairment at Visit 1. [22] 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. [23] 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. [24] Any evidence of heart disease (New York Heart Association [NYHA] greater than or equal to Class III within 6 months of Visit 1. [25] Systolic blood pressure >160 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at Visit 1, or malignant hypertension. [26] Scheduled or planned surgery during the course of the study. [27] History of significant central nervous system injuries (including stroke or spinal cord injury) within 6 months of Visit 1. [28] History of drug, alcohol, or substance abuse within 6 months of Visit 1. [29] 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. [30] Current treatment with nitrates, androgens, antiandrogens, estrogens, luteinizing hormone releasing hormone agonists/antagonists, or anabolic steroids. [31] Current systemic treatment with any of the following: [a] Potent cytochrome P450 3A4 (CYP3A4) inhibitors, such as ketoconazole or ritonavir. [b] CYP3A4 inducer rifampicin. [32] Glycosylated hemoglobin (HbA1c) >9% at Visit 1. [33] Known or suspected hypersensitivity to tadalafil or any study drug components. [34] Are investigator site personnel directly affiliated with this study and/or their immediate families. [35] Are Lilly employees (defined in protocol). [36] Previously completed or withdrawn from this study or any other study investigating tadalafil. [37] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. Subjects who have been screen failures in previous studies may be eligible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in IPSS from baseline after 12 weeks. |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
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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
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |