E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Men with 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 LVHJ is 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 |
Evaluate the change of tadalafil 5 mg daily for 12 weeks compared with placebo daily for 12 weeks in the treatment of men with BPH-LUTS as assessed by the following measures:IPSS storage, voiding and nocturnias subscore,IPSS Quality of Life Index,BPH Impact Index,Patient Global Impression of Improvement,Clinician Global Impression of Improvement,Voiding dribble diary-To evaluate the change 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 of tadalafil 5 mg compared with placebo after 4 weeks of treatment in men with BPH-LUTS as assessed by the following measures:IPSS,BII. To examine the impact of tadalafil 5 mg for 12 weeks on erectile function in men with both BPH-LUTS and erectile dysfunction as assessed by the IIEF EF Domain.To assess the safety of tadalafil 5 mg for 12 weeks in the treatment of men with BPH-LUTS as examined by:Adverse events,Vital signs,Clinical laboratory tests,PRV |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Present with benign prostatic hyperplasia (BPH; also referred to as BPH LUTS based on the disease diagnostic criteria at V1. 2.Are men 45 years of age or older at V1. 3.Provide signed informed consent at V1. 4.Agree not to use any other approved or experimental pharmacologic BPH, overactive bladder, or erectile dysfunction 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 V2,Dutasteride therapy for at least 6 months prior to V2,All other BPH therapy for at least 4 weeks prior to V2.OAB therapy for at least 4 weeks prior to V2, ED therapy for at least 4 weeks prior to V2. 6.Have LUTS with a Total International Prostate Symptom Score (IPSS) >/=13 at V2. 7.Have bladder outlet obstruction as defined by a urinary peak flow rate (Qmax) of >/=4 to </=15 mL/second at V2. 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 V3. |
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E.4 | Principal exclusion criteria |
9.PSA>10.0 ng/mL at V1.10.PSA >/=4.0 to </=10.0 ng/mL at V1 if prostate malignancy has not been ruled out to the satisfaction of the investigator.11.Bladder PVR>/=300 mL by ultrasound determination at V1.12.History of any of the following pelvic conditions:Pelvic surgery or any other pelvic procedure, including radical prostatectomy, pelvic surgery for removal of malignancy, or bowel resection;Pelvic radiotherapy;Any pelvic surgical procedure of the urinary tract, including minimally invasive BPH LUTS therapies and penile implant surgery.Lower urinary tract malignancy or trauma.13.Lower urinary tract instrumentation (including prostate biopsy) within 30 days of V1.14.History of urinary retention or lower urinary tract (bladder) stones within 6 months of V1.15.History of urethral obstruction due to stricture, valves, sclerosis, or tumor.16.Clinical evidence of any of the following bladder conditions:Mullerian duct cysts,Atonic, decompensated, or hypocontractile bladder,Detrusor-sphincter dyssynergia, Intravesical obstruction,Interstitial cystitis.17.Clinical evidence of any of the following urinary tract conditions at V1:Urinary tract infection,Urinary tract inflammation,Current antibiotic therapy for urinary tract infection.18.Clinical evidence of prostate cancer.19Current 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 V121.Clinical evidence of severe hepatic impairment at V1.22.History of any of the following cardiac conditions:Angina requiring treatment with long-acting nitrates,Angina requiring treatment with short-acting nitrates within 90 days of V1,Unstable angina within 90 days of V1,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 V1:Myocardial infarction,Coronary artery bypass graft surgery,Percutaneous coronary intervention. 24.Any evidence of heart disease (New York Heart Association [NYHA] >/= Class III within 6 months of V1.25.Systolic blood pressure >160 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at V1 or malignant hypertension.26.Scheduled or planned surgery during the course of the study. 27.History of significant central nervous system injuries within 6 months of V1.28.History of drug, alcohol, or substance abuse within 6 months of V1.29.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:Potent cytochrome P450 3A4 (CYP3A4) inhibitors,CYP3A4 inducer rifampicin.32.Glycosylated hemoglobin >9% at V1. 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.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.38.History of loss of vision in 1 eye because of nonarteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous phosphodiesterase type 5 (PDE5) inhibitor exposure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change 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 | 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.8.4.1 | 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 | 0 |
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 years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |