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 | 14.0 |
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 |
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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 LVIR is to 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. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are as follows: •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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects are eligible to be included in the study only if they meet all of the following criteria: [1] Present with benign prostatic hyperplasia (BPH; also referred to as BPH-LUTS [lower urinary tract symptoms]) 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 (including herbal preparations and vitamin preparations containing saw palmetto) 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 [assessed by ultrasound] 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. |
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E.4 | Principal exclusion criteria |
[8] Prostate specific antigen (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 by ultrasound determination at screening [11] History of any of the following pelvic conditions: • 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 conditions at screening: • 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 at the start of the TRUS assessment period or other findings related to prostate anatomy on screening TRUS that may interfere with measurement of ultrasound blood flow parameters • 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 • Angina 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 mm Hg or diastolic blood pressure >100 or <50 mm Hg at screening (if stress is suspected, retest under basal conditions) 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, would place subject at increased risk, or might confound the interpretation of the study results [31] Current treatment with nitrates (as outlined in Exclusion Criterion 24), 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 any of the following: • Potent cytochrome P450 3A4 inhibitors • CYP3A4 inducer rifampicin [33] Previously received pharmacological treatment for BPH-LUTS (alpha-blockers or 5-alpha reductase inhibitors) and failed to have a clinical response [34] Glycosylated hemoglobin (HbA1c) >9% at Visit 1. [35] Have a body mass index ≥ 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] Are investigator site personnel directly affiliated with this study and/or their immediate families [40] Are Lilly employees [41] Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study [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 nonarteritic anterior ischemic optic neuropathy |
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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. |
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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 | 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 |
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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 | 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 | 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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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |