E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Benign Prostatic Hyperplasia (BPH) |
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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 |
Change from baseline in International Prostate Symptom Score (IPSS) at 12 weeks, tadalafil compared with placebo. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the: - Change from baseline in International Prostate Symptom Score (IPSS) at 12 weeks, tamsulosin compared with placebo. - Change from baseline in modified International Prostate Symptom Score (mIPSS) at 1 week) and in IPSS at 4 weeks. - Change from baseline at 12 weeks in the International Index of Erectile Function - Erectile Function Domain (IIEF-EF). - Uroflowmetry measurements. -safety of tadalafil in treating BPH.
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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 |
- Addendum 1 (version 22 April 2009) / NAION Addendum Title: 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 Symptomsof Benign Prostatic Hyperplasia
Rationale: Some countries participating in Protocol H6D-MC-LVID have a contraindication for subjects with a history of vision loss due to nonarteritic anterior ischemic optic neuropathy (NAION). Therefore, an exclusion criterion (number 40) for these subjects is being added for consistency with the local CIALIS® (tadalafil) label. The exclusion criterion is only for those participating countries where this contraindication is in effect. |
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E.3 | Principal inclusion criteria |
-Men 45 years of age or older at Screening Visit. -Provide signed informed consent at Screening Visit. -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. -Have not taken the following treatments within the indicated duration: [a] Finasteride therapy for at least 3 months prior to Placebo Lead in Visit. [b] Dutasteride therapy for at least 6 months prior to Placebo Lead in Visit. [c] Other BPH therapy (including herbal preparations) for at least 4 weeks prior to Placebo Lead in Visit. [d] OAB therapy for at least 4 weeks prior to Placebo Lead in Visit. [e] ED therapy for at least 4 weeks prior to Placebo Lead in Visit. [f] Other experimental or off-label BPH therapy, such as injectable therapies with a protracted effect, for at least 1/2 year prior to Placebo Lead in Visit. -Have LUTS with a Total IPSS >=13 at Placebo Lead in Visit. -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 Placebo Lead in Visit. -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 Randomization Visit. |
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E.4 | Principal exclusion criteria |
-PSA >10.0 ng/mL at Screening Visit. -PSA >=4.0 to <=10.0 ng/mL at Screening Visit if prostate malignancy has not been ruled out to the satisfaction of an urologist. -Bladder PVR >=300 mL by ultrasound determination at Screening Visit. -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 Screening Visit. -History of urinary retention or lower urinary tract stones within 6 months of Screening Visit. -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 Screening Visit : [a] Urinary tract infection. [b] Urinary tract inflammation. [c] Current antibiotic therapy for urinary tract infection. [d] Clinically 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, defined as receiving renal dialysis or having an estimated creatinine clearance <30 mL/minute at Screening Visit as calculated by the central laboratory using the Cockroft-Gault Formula. -Clinical evidence of severe hepatic impairment at Screening Visit. -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 Screening Visit. [c] Unstable angina within 90 days of Screening Visit. [d] Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention. -History of any of the following coronary conditions within 90 days of Screening Visit : [a] Myocardial infarction. [b] Coronary artery bypass graft surgery. [c] Percutaneous coronary intervention. -Any evidence of heart disease (New York Heart Association [NYHA] >=Class III within 6 months of Screening Visit. -Systolic blood pressure >160 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at Screening Visit, or malignant hypertension. -Scheduled or planned surgery during the course of the study. -Scheduled or planned cataract surgery during the course of the study due to risk of intraoperative floppy iris syndrome (IFIS). -History of significant central nervous system injuries within 6 months of Screening Visit. -History of drug, alcohol, or substance abuse within 6 months of Screening Visit. -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, or anabolic steroids. -Current systemic treatment with any of the following: [a] Potent cytochrome P450 3A4 (CYP3A4) inhibitors, such as ketoconazole or ritonavir. [b] Potent CYP3A4 inducer, such as rifampicin. -Glycosylated hemoglobin (HbA1c) >9% at Screening Visit. -Known or suspected hypersensitivity to tadalafil, tamsulosin or any study drug components. -History of symptomatic orthostatic hypotension, recurrent episodes of dizziness, vertigo, loss of consciousness, or syncope. -Are investigator site personnel directly affiliated with this study and/or their immediate families. -Are Lilly employees. -Previously completed or withdrawn from this study or any other study investigating tadalafil. -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, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Subjects who have been screen failures in previous studies may be eligible.
Exclusion criteria relative to Addendum 1 (version 22 April 2009) / NAION Addendum: -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 in IPSS 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 | 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.8.5 | 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 |
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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 | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |