| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Benign Prostatic Hyperplasia (BPH) |
| Ipertrofia prostatica benigna |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10004446 |
| E.1.2 | Term | Benign prostatic hyperplasia |
| E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
|
| 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 |
| Evaluate the effect of tadalafil 5 mg once daily for 8 weeks compared with placebo on improving prostatic blood perfusion in men with signs and symptoms of BPH, also referred to as BPH-LUTS (lower urinary tract symptoms), as measured by arterial resistive index (RI) in the prostate transition zone |
| Valutare l’effetto di tadalafil 5 mg somministrato una volta/die per 8 settimane vs. placebo nel migliorare la perfusione ematica prostatica negli uomini con segni e sintomi di BPH, valutata mediante l’indice di resistenza (RI) arterioso nella zona di transizione della prostata. |
|
| E.2.2 | Secondary objectives of the trial |
| - To evaluate the effect of tadalafil 5 mg once daily for 8 weeks versus placebo on other regional blood flow and perfusion parameters in the prostate as measured by: Color Doppler ultrasound pixel intensity (color pixel intensity, CPI) in the prostate transition zone and arterial RI and CPI in prostate peripheral zone. - To evaluate the effect of tadalafil 5 mg once daily for 8 weeks versus placebo on blood flow and perfusion parameters in the bladder neck as measured by arterial RI and CPI. - To evaluate the effect of tadalafil 5 mg once daily for 4 weeks versus placebo on all of the above blood flow and perfusion parameters in the prostate and bladder neck |
-Valutare l’effetto di tadalafil 5 mg somministrato una volta/die per 8 settimane vs.placebo su altri parametri di flusso ematico e perfusione regionale nella prostata mediante:- intensita' dei pixel del Color Doppler (CPI) nella zona di transizione della prostata;- RI arterioso e CPI nella zona periferica della prostata.
- Valutare l’effetto di tadalafil 5 mg somministrato una volta/die per 8 settimane vs.placebo sui parametri di flusso ematico e perfusione nel collo della vescica mediante RI arterioso e CPI.
- Valutare l’effetto di tadalafil 5 mg somministrato una volta/die per 4 settimane vs.placebo su tutti i suddetti parametri di flusso ematico e perfusione nella prostata e nel collo della vescica |
|
| 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 at screening. 2. Are men 45 years of age or older at screening. 3. Provide signed informed consent at screening. 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: Finasteride therapy for at least 3 months prior to the TRUS assessment period, Dutasteride therapy for at least 6 months prior to the TRUS assessment period, All other BPH therapy for at least 4 weeks prior to the TRUS assessment period, Overactive bladder therapy for at least 4 weeks prior to the TRUS assessment period, ED therapy for at least 4 weeks prior to the TRUS assessment period, Any other experimental or off-label BPH therapy, such as injectable therapies with a protracted effect, for at least 6 months prior to the TRUS assessment period. 6 Have LUTS with a total IPSS >/= 13 under 1 of the following conditions: At screening if the subject does not require wash-out of therapy for BPH-LUTS. At the start of the TRUS assessment period if the subject requires wash-out (4 weeks) of BPH-LUTS therapy. 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 of >/= 150 to </= 550 mL and a minimum voided volume of 125 mL) under 1 of the following conditions: At screening if the subject does not require wash-out of therapy for BPH-LUTS. At the start of the TRUS assessment period if the subject requires wash-out (4 weeks) of BPH-LUTS therapy |
| 1. Presenza di ipertrofia prostatica benigna allo screening. 2. Uomini di eta' maggiore/uguale a 45 anni allo screening. 3. Firma del modulo per il consenso informato allo screening. 4 Accettare di non utilizzare altri farmaci approvati o in sperimentazione per BPH, vescica iperattiva (OAB), o disfunzione erettile (DE), compresi alfa bloccanti, gli inibitori della 5-alfa reduttasi (5-ARIs), antimuscarinici, inibitori della fosfodiesterasi di tipo 5 (PDE5), o preparazioni a base di erbe, in qualsiasi momento durante lo studio. 5 Non siano i trattamento con: Finasteride per almeno 3 mesi prima del periodo di valutazione TRUS, Dutasteride per almeno 6 mesi precedenti il periodo di valutazione TRUS, Altre terapie per BPH per almeno 4 settimane prima per il periodo di valutazione TRUS, altre terapie per vescica iperattiva per almeno 4 settimane prima del termine per la valutazione TRUS, Altre terapie per disfunzione erettile per almeno 4 settimane prima del termine per la valutazione TRUS, Altri trattamenti sperimentali o non in indicazione per BPH, come le terapie iniettabili con un effetto prolungato, per almeno 6 mesi precedenti il periodo di valutazione TRUS. 6 LUTS con IPSS totale >/= 13: allo screening se il soggetto non ha bisogno di wash-out da terapia per BPH-LUTS, oppure all'inizio del periodo di valutazione TRUS se e' richiesto wash-out (4 settimane) dalla terapia BPH-LUTS. 7 Ostruzione della vescica, definita da una velocita' di picco di flusso urinario (Qmax) >/= 4 e </= 15 ml / secondo (da un volume totale preminzione > / = 150 e </ = 550 ml e un volume svuotato minimo di 125 ml): allo screening se il soggetto non ha bisogno di wash-out da terapia per BPH-LUTS, oppure all'inizio del periodo di valutazione TRUS se e' richiesto wash-out (4 settimane) dalla terapia BPH-LUTS. |
|
| E.4 | Principal exclusion criteria |
| 8.(PSA)>10.0 ng/mL at screening. 9.PSA>/= 4.0 to </=10.0 ng/mL at screening if prostate malignancy has not been ruled out to the satisfaction of a urologist. 10.Bladder postvoid residual volume >/= 300 mL at screening. 11.History of: Pelvic surgery or any other pelvic procedure;Pelvic radiotherapy ;Any pelvic surgical procedure of the urinary tract;Lower urinary tract malignancy or trauma. 12.Lower urinary tract instrumentation within 30 days of screening. 13.History of urinary retention or lower urinary tract stones within 6 months of screening. 14.History of urethral obstruction due to stricture,valves,sclerosis,or tumor . 15. Clinical evidence or medical history of any of the following bladder conditions:Mullerian duct cysts;Atonic,decompensated or hypocontractile bladder;Detrusor-sphincter dyssynergia;Intravesical obstruction;Interstitial cystitis. 16.Clinical evidence of any of the following:Urinary tract infection;Urinary tract inflammation;Current antibiotic therapy for urinary tract infection;Clinically significant microscopic hematuria. 17.Clinical evidence of prostate cancer. 18.History of prostate saturation biopsy.19.Any condition which may preclude or negatively influence tolerance to TRUS. 20.Clinical evidence on TRUS of any of the following prostate conditions:Prominent median or midline lobe;Multiple prostatic cystic changes or multiple calcifications;Scarring from previous prostate biopsies. 21.Current neurologic disease or condition associated with neurogenic bladder. 22.History of significant renal insufficiency. 23.Clinical evidence of severe hepatic impairment at screening. 24.History of any of the following cardiac conditions:Angina requiring treatment with long-acting nitrates;and requiring treatment with short-acting nitrates within 90 days of screening;Unstable angina within 90 days of screening;Positive cardiac stress test without documented evidence of subsequent,effective cardiac intervention. 25.History of any of the following coronary conditions within 90 days of screening:Myocardial infarction;Coronary artery bypass graft surgery;Percutaneous coronary intervention. 26.Any evidence of moderate to severe cardiac disease within 6 months of screening. 27.Systolic blood pressure >160 or < 90 mmHg or diastolic blood pressure >100 or <50 mmHg at screening or malignant hypertension. 28.Scheduled or planned surgery during the course of the study. 29.History of drug,alcohol,or substance abuse within 6 months of screening. 30.Any condition that would interfere with subject ability to provide informed consent or comply with study instructions. 31.Current treatment with nitrates,androgens, antiandrogens,estrogens,luteinizing hormone-releasing hormone agonists/antagonists,anabolic steroids,or non-prescription products containing estrogenic or androgenic supplements. 32.Current systemic treatment with:Potent cytochrome P450 3A4 inhibitors,CYP3A4 inducer rifampicin. 33.Previously received pharmacological treatment for BPH-LUTS and failed to have a clinical response. 34.HbA1c >9% at Visit 1. 35.Have a BMI >/= 35 kg/m2 at Visit 1. 36.Invalid or unevaluable results from both the original and repeat baseline TRUS. 37.Known or suspected hypersensitivity to tadalafil or any study drug components. 38.Previously completed or withdrawn from this study or any other study investigating tadalafil. 39.Investigator site personnel directly affiliated with this study and/or immediate families. 40.Lilly employees. 41.Currently enrolled in, or discontinued within the last 30 days from a clinical trial. 42.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. 43.History of loss of vision in 1 eye because of NAION |
| 8. (PSA)>10,0 ng/mL a screening. 9.PSA>/= 4,0 e </= 10.0 ng/mL se tumore maligno della prostata non e' stato escluso dal medico urologo. 10.Volume residuo>/= 300 mL allo screening. 11.Storia di:chirurgia pelvica o qualsiasi altra procedura pelvica;radioterapia pelvica;Qualsiasi procedura chirurgica pelvica delle vie urinarie,neoplasie del tratto urinario inferiore o trauma. 12.Indagini strumentali del tratto urinario entro 30 giorni dallo screening. 13.Storia di ritenzione urinaria o calcoli alle vie urinatrie entro 6 mesi dallo screening. 14.Storia di ostruzione uretrale a causa di stenosi,valvole,sclerosi, o tumore. 15.Evidenza clinica di:Cisti del dotto Mullerian;vescica atoniche,scompensata o ipocontrattile;dissinergia del detrusore-sfintere,ostruzione intravescicale,cistite interstiziale. 16.Evidenza clinica di:infezioni del tratto urinario,infiammazione delle vie urinarie, attuale terapia antibiotica per l'infezione del tratto urinario;ematuria microscopica. 17.Evidenza clinica di cancro alla prostata. 18.Biopsia prostatica.19.Ogni condizione di saturazione della prostata che puo' precludere o influenzare negativamente la tolleranza al TRUS. 20.Evidenza clinica mediante TRUS di: lobo mediano prominente o linea mediana;cisti prostatiche multiple o calcificazioni multiple;cicatrici da biopsie prostatiche. 21.Malattie neurologiche o condizioni associate a vescica neurogena. 22.Insufficienza renale significativa. 23.Insufficienza epatica significativa allo screening. 24.Storia di una delle seguenti condizioni cardiache:angina che richiede trattamento con nitrati a lunga durata e a breve durata di azione entro 90 giorni dallo screening,angina instabile entro 90 giorni dallo screening;test di stress cardiaco positivo,intervento cardiaco. 25.Storia di una qualsiasi delle seguenti condizioni coronariche entro 90 giorni dallo screening:infarto del miocardio;bypass aortocoronarico;intervento coronarico percutaneo. 26.Evidenza di grado da moderato a grave di malattia cardiaca nei 6 mesi di screening.27.Pressione arteriosa sistolica > 160 e <90 mmHg o pressione diastolica > 100 o <50 mmHg o ipertensione maligna. 28.Intervento chirurgico durante il corso dello studio. 29.Storia di droga, alcool o abuso di sostanze nei 6 mesi di screening. 30.Condizioniche potrebbero interferire con la capacita' oggetto di fornire un consenso informato o seguire le istruzioni di studio. 31.Trattamento con nitrati,androgeni,antiandrogeni,estrogeni,agonisti/antagonisti dell’ormone luteinizzante,steroidi anabolizzanti,supplementi contenenti estrogeni o androgeni. 32.Trattamento sistemico con:inibitori potenti del citocromo P450 3A4,rifampicina,induttori del CYP3A4. 33.Trattamento farmacologico precedente per BPH-LUTS che non hanno dimostrato efficacia clinica. 34.HbA1c> 9% a visita1. 35. BMI>/= 35 kg/m2 alla visita1. 36.Risultati non validi o non valutabili della TRUS basale. 37.Nota o sospetta ipersensibilita' al tadalafil o ad uno dei componenti del farmaco in studio. 38.Partecipazione a questo studio o ad ogni altro studio su tadalafil. 39.Sperimentatori di studio e familiari. 40.Dipendenti Lilly. 41.Pazienti arruolati o che hanno interrotto uno studio clinico negli ultimi 30 giorni. 42.Trattamento negli ultimi 30 giorni con un farmaco che non ha ricevuto l'approvazione per qualsiasi indicazione,al momento dell'ingresso nello studio. 43.Storia di perdita della vista a un occhio a causa di NAION |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint, and basis for comparison between treatment groups, will be the change from baseline in prostatic transitional zone resistive index (RI) from baseline to Week 8 |
| L’endpoint primario di questo studio e' rappresentato dall’RI arterioso nella zona di transizione della prostata |
|
| 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 | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 15 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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