E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Benign prostatic hyperplasia and erectile dysfunction. |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061461 |
E.1.2 | Term | Erectile dysfunction |
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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 once daily for 12 weeks compared with placebo in improving both IPSS and IIEF Erectile Function (EF) Domain in men with both ED and signs and symptoms of BPH.
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E.2.2 | Secondary objectives of the trial |
- efficacy of tadalafil 2.5 & 5 mg daily for 12 weeks v placebo in improving Patient Sexual Encounter Profile (SEP) diary Question 3 - efficacy of tadalafil 2.5 & 5 mg daily for 12 weeks v placebo in improving BII. - safety of tadalafil 2.5 & 5 mg daily for 12 weeks - change in mIPSS from baseline to 2 weeks for tadalafil 2.5 & 5 mg daily v placebo - change in IPSS, IIEF EF Domain, SEP diary Question 3, and BII from baseline to 4 and 8 weeks for tadalafil 2.5 & 5 mg daily v placebo - change in IPSS subscores, IIEF Overall and Intercourse Satisfaction Domains, IIEF Questions 3 & 4, and SEP diary Questions 2, 4 & 5 from baseline to 4, 8, & 12 weeks for tadalafil 2.5 & 5 mg daily v placebo - impact of tadalafil 2.5 & 5 mg daily for 12 weeks v placebo on urinary symptoms of BPH-LUTS - impact of tadalafil 2.5 & 5 mg daily for 12 weeks v placebo on improving erectile function - change in uroflowmetry parameters from baseline to 12 weeks for tadalafil 2.5 & 5 mg daily v placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- men 45 years of age or older at Visit 1. - present with BPH-LUTS based on the disease diagnostic criteria (Protocol Section 8.1.1 and have a history of ED based on the disease diagnostic criteria (Protocol Section 8.1.2) at Visit 1. - have LUTS with a Total IPSS ≥13 at Visit 2. - have bladder outlet obstruction (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) at Visit 2. - make at least 4 sexual intercourse attempts during the 4-week placebo lead-in period. - are sexually active with an adult female partner, and expect to remain sexually active with the same adult female partner for the duration of the study. - demonstrate compliance with study drug administration requirements during the placebo lead-in period by administering ≥70% of prescribed doses. - agree not to use any other approved or experimental pharmacologic BPH, OAB, or ED treatments, including alpha blockers, 5-ARIs, antimuscarinics, PDE5 inhibitors, or herbal preparations, at any time during the study. - 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 (including herbal preparations) for at least 4 weeks prior to Visit 2. [10] Provide signed informed consent at Visit 1. |
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E.4 | Principal exclusion criteria |
- PSA >10.0 ng/mL at Visit 1. - PSA ≥4.0 to ≤10.0 ng/mL at Visit 1 if prostate malignancy has not been ruled out by a urologist. - bladder PVR ≥300 at Visit 1. - 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. - lower urinary tract instrumentation within 30 days of Visit 1. - history of urinary retention or lower urinary tract (bladder) stones within 6 months - clinical evidence of severe hepatic impairment at Visit 1. - history of urethral obstruction due to stricture, valves, sclerosis, or tumor. - 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. - 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] Significant microscopic hematuria as determined by a urologist. - clinical evidence of prostate cancer. - current neurologic disease or condition associated with neurogenic bladder. - history of significant renal insufficiency (receiving renal dialysis or an estimated creatinine clearance <30 mL/minute at Visit 1 as calculated using the Cockroft-Gault formula). - history of ED caused by other primary sexual disorders including premature ejaculation or ED caused by untreated endocrine disease. - presence of penile deformity judged by the investigator to be clinically significant. - history of any of the following cardiac conditions: [a] Chronic stable angina treated 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] Angina occurring during sexual intercourse in the last 6 months. [e] Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention. - 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. - new significant cardiac conduction defect within 90 days prior to Visit 1. - any supraventricular arrhythmia with an uncontrolled ventricular at rest despite medical or device therapy, or any history of spontaneous or induced sustained ventricular tachycardia despite medical or device therapy, or the presence of an automatic internal cardioverterdefibrillator. - history of resuscitated cardiac arrest. - any evidence of heart disease (New York Heart Association [NYHA] ≥ Class II) within 6 months of Visit 1. - systolic blood pressure >160 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at Visit 1 or malignant hypertension. - history of human HIV infection. - scheduled or planned surgery during the course of the study. - history of significant central nervous system injuries within 6 months of Visit 1. - history of drug, alcohol, or substance abuse within 6 months of Visit 1. - 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. - current treatment with nitrates, androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone agonists/antagonists, anabolic steroids, or cancer chemotherapy. - current systemic treatment with any of the following: [a] Potent cytochrome P450 3A4 (CYP3A4) inhibitors. [b] CYP3A4 inducers. - HbA1c >9% at Visit 1. - known or suspected hypersensitivity to tadalafil or any study drug components. - prior treatment with PDE5 inhibitors judged by the investigator to be ineffective. - are investigator site personnel directly affiliated with this study and/or their immediate families. - are Lilly employees and their immediate family. - are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug or device (other than the study drug used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. - have previously completed or withdrawn from this study or any other study investigating tadalafil. 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) |
Mean changes from baseline to the end of therapy in Total IPSS and IIEF EF Domain Score. |
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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 | Information not present in EudraCT |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |