E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Benign Prostatic Hyperplasia |
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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 |
The primary objective of Study LVHG is to test the hypothesis that tadalafil 5 mg once a day for 12 weeks is superior to placebo in improving the International Prostate Symptom Score (IPSS) in men with signs and symptoms of benign prostatic hyperplasia (also referred to as BPH-LUTS [lower urinary tract symptoms]). |
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E.2.2 | Secondary objectives of the trial |
To examine whether a dose-response relationship exists for placebo and tadalafil 2.5 mg, 5 mg, 10 mg, and 20 mg once a day for 12 weeks in the treatment of BPH-LUTS. To test the hypothesis that tadalafil 5 mg once a day for 12 weeks is superior to placebo in the treatment of BPH-LUTS as assessed by uroflowmetry parameters and the scores obtained in the following questionnaires:IPSS, BPH Impact Index (BII), LUTS Global Assessment Question (LUTS GAQ) To examine the impact of tadalafil once a day on erectile function in men with both BPH-LUTS and Erectile Disfunction. To assess the safety of tadalafil 2.5 mg, 5 mg, 10 mg, and 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,electrocardiograms (ECGs),prostate-specific antigen (PSA)and postvoid residual volume (PVR). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
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 ICD at Visit 1. [4] Agree not to use any other approved or experimental pharmacologic BPH or ED treatments 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 12 months prior to Visit 2.[c] All other BPH therapy (including herbal preparations) for at least 4 weeks prior to Visit 2.[d] ED therapy for at least 4 weeks prior to Visit 2. [6] Have LUTS with a total IPSS >=13 at Visit 2. [7] Have bladder outlet obstruction as defined by a urinary peak flow rate (Qmax) of >=4 to <=15 mL/second (from a prevoid total bladder volume [assessed by ultrasound] of >=150 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 run-in period by administering >=70% of prescribed doses, confirmed by documentation that the subject returned <=30% of prescribed doses at Visit 3. |
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E.4 | Principal exclusion criteria |
[1] PSA >10.0 ng/mL at Visit 1. [2] PSA >=4.0 to <=10.0 ng/mL at Visit 1 without documentation of a histologic biopsy of the prostate negative for cancer within 12 months of Visit 1. [3] Bladder PVR >=300 mL by ultrasound determination 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, including penile implant surgery.[d] Lower urinary tract malignancy or trauma. [5] Lower urinary tract instrumentation (including prostate biopsy) within 30 days of Visit 1. [6] History of urinary retention or lower urinary tract (bladder) stones within 6 months of Visit 1. [7] History of urethral obstruction due to stricture, sclerosis, or tumor. [8] Clinical evidence of any of the following bladder conditions:[a] Mullerian duct cysts. [b] Bladder calculi.[c] Atonic or hypocontractile bladder.[d] Detrusor-sphincter dyssynergia. [9] 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. [10] History of intravesical obstruction. [11] Clinical evidence of prostate cancer. [12] Current neurologic disease or condition associated with neurogenic bladder. [13] History of significant renal insufficiency. [14] Clinical evidence of hepatic impairment at Visit 1. [15] History of Angina or positive cardiac stress test. [16] 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 (for example, angioplasty or stent placement). [17] Any evidence of heart disease within 6 months of Visit 1. [18] Systolic blood pressure >180 or <90 mm Hg or diastolic blood pressure >110 or <50 mm Hg at Visit 1 (if stress is suspected, retest under basal conditions), or malignant hypertension. [19] Scheduled or planned surgery (or any procedure requiring general anesthesia) during the course of the study. [20] History of significant central nervous system (CNS) injuries within 6 months of Visit 1. [21] History of drug, alcohol, or substance abuse within 6 months of Visit 1. [22] Current treatment with nitrates, cancer chemotherapy, androgens, antiandrogens,estrogens, LHRH agonists/antagonists, or anabolic steroids. [23] Current systemic treatment with a potent cytochrome P450 3A4 inhibitor [24] Glycosylated hemoglobin (HbA1c) >11% at Visit 1. [25]History of loss of vision in one eye because of nonarteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change in total IPSS change from baseline to Week 12. |
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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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |