E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Benign Prostatic Hyperplasia |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
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 |
The primary objective of Study LVID is to evaluate the efficacy of tadalafil 5 mg once daily (QD) 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]). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are as follows: To evaluate the efficacy of tamsulosin 0.4 mg QD for 12 weeks compared with placebo in improving IPSS in men with BPH-LUTS. To evaluate the efficacy of tadalafil 5 mg QD compared with placebo and tamsulosin 0.4 mg QD compared with placebo for 12 weeks in the treatment of men with BPH-LUTS as assessed by the following measures: - BPH Impact Index (BII) - IPSS storage (irritative) subscore - IPSS voiding (obstructive) subscore - IPSS nocturia subscore - IPSS Quality of Life (QoL) Index - Patient Global Impression of Improvement (PGI-I) - Clinician Global Impression of Improvement (CGI-I) - The Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) To evaluate the efficacy of tadalafil 5 mg QD compared with placebo and tamsulosin 0.4 mg QD compared with placebo after 1 week of treatment in men with BPH-LUTS as assessed by the Modified IPSS (mIPSS). |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA: Versione:Addendum 2 Data:2009/04/22 Titolo:Protocol Sample Banking Addendum H6D-MC-LVID(2) A Phase 3, Randomized, Double-Blind, Placebo- Controlled, Parallel-Design, Global Multicenter Study to Evaluate the Efficacy and Safety of Tadalafil Once Daily Dosing for 12 Weeks in Men with Signs and Symptoms of Benign Prostatic Hyperplasia Obiettivi:Lo Sposor ha incluso questo studio nel programma CSB (Combined Specimen Banking), per la raccolta e conservazione collettiva dei campioni in una Banca di campioni provenienti da pazienti che hanno partecipato a studi Eli Lilly & Company. I campioni di questa Banca sono raccolti e conservati a scopi di ricerca, per identificare geni, prodotti genici e marker biochimici associati con le patologie e le risposte ai trattamenti in sperimentazione e ad altri eventuali farmaci utilizzati durante la sperimentazione. Nello studio H6D-MC-LVID, possono essere oggetto di ricerca: la relazione in geni candidati, marcatori di infiammazione come la proteina C-reattiva, tra le varianti genetiche che si costituiscono in modo naturale e l immunomodulazione attraverso inibitori della fosfodiesterasi come il tadalafil.
|
|
E.3 | Principal inclusion criteria |
[1] Present with BPH (also referred to as BPH-LUTS) based on the disease diagnostic criteria (Section 8.1.1) 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] 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. [f] Other experimental or off-label BPH therapy, such as injectable therapies with a protracted effect, for at least 1/2 year 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 (see Protocol Attachment LVID.3). [8] Demonstrate compliance with study drug administration requirements during the placebo lead-in period by administering ≥70% of prescribed doses, confirmed by documentation that the subject returned ≤30% of prescribed doses at Visit 3 |
|
E.4 | Principal exclusion criteria |
[9] Prostate-specific antigen (PSA) >10.0 ng/mL at Visit 1. [10] PSA &#8805;4.0 to &#8804;10.0 ng/mL at Visit 1 if prostate malignancy has not been ruled out to the satisfaction of an urologist. [11] Bladder PVR &#8805;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, including radical prostatectomy, pelvic surgery for removal of malignancy, or bowel resection. [b] Pelvic radiotherapy. [c] Any pelvic surgical procedure of the urinary tract, including minimally invasive BPH-LUTS therapies and penile implant surgery. [d] Lower urinary tract malignancy or trauma. [13] Lower urinary tract instrumentation (including prostate biopsy) within 30 days of Visit 1. [14] History of urinary retention or lower urinary tract (bladder) 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 (contraction of the detrusor without sphincter relaxation). [d] Intravesical obstruction (for example, intravesical median lobe of the prostate). [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 (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. [c] Current antibiotic therapy for urinary tract infection. [d] Clinically significant microscopic hematuria as determined by a urologist. [18] Clinical evidence of prostate cancer. [19] Current neurologic disease or condition associated with neurogenic bladder (for example, Parkinsons disease, multiple sclerosis). [20] History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance <30 mL/minute at Visit 1 as calculated by the central laboratory using the Cockroft-Gault formula: (140 &#8722; age [years]) � weight [kg] / (72 � serum creatinine [mg/dL]) [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 as defined in Protocol Attachment LVID.4 (Braunwald 1989) 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 (for example, angioplasty or stent placement). [24] Any evidence of heart disease (New York Heart Association [NYHA] &#8805; Class III as defined in Protocol Attachment LVID.5 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 (if stress is suspected, retest under basal conditions), or malignant hypertension. [26] Scheduled or planned surgery (or any procedure requiring general, spinal, or epidural anesthesia) during the course of the study. [27] Scheduled or planned cataract surgery during the course of the study due to risk of intraoperative floppy iris syndrome (IFIS). [28] History of significant central nervous system injuries (including stroke or spinal cord injury) within 6 months of Visit 1. [29] History of drug, alcohol, or substance abuse within 6 mo |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Tadalafil 5 mg QD resulted in a clinically and statistically significant improvement in IPSS (primary endpoint) compared with placebo after 12 weeks. |
|
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) | Yes |
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 | 43 |
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
|
ultima visita dell`ultimo paziente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
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 | 4 |