| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Benign Prostatic Hyperplasia (BPH) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10004446 |
| E.1.2 | Term | Benign prostatic hyperplasia |
|
| 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 this study is to test the hypothesis that tadalafil 5 mg once daily co-administered with finasteride is superior to placebo once daily co-administered with finasteride for 12 weeks in improving the International Prostate Symptom Score (IPSS) in men with lower urinary tract symptoms (LUTS) and prostatic enlargement secondary to benign prostatic hyperplasia (BPH). |
|
| E.2.2 | Secondary objectives of the trial |
•To examine the impact of tadalafil 5 mg once daily versus placebo when co-administered with finasteride on erectile function in men with LUTS and prostatic enlargement secondary to BPH at 4, 12 and 26 weeks.
•To evaluate the change from baseline of tadalafil 5 mg once daily versus placebo when coadministered with finasteride in the treatment of men with LUTS and prostatic enlargement secondary to BPH
•To examine the impact of tadalafil 5 mg once daily versus placebo when coadministered with finasteride on urinary symptoms of BPH assessed at 26 weeks in men with LUTS and prostatic enlargement secondary to BPH
•To assess the safety of tadalafil 5 mg once daily versus placebo when co-administered with finasteride for 26 weeks in the treatment of men with LUTS and prostatic enlargement secondary to BPH, as examined by the following measures: adverse events; vital signs; clinical laboratory tests; and Postvoid residual volume. |
|
| 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 |
| 1. Sample Banking Addendum H6D-CR-LVIW(1), version 11 May 2010: Variable response to LY450190 may be due to genetic determinants that impact drug absorption, distribution, metabolism, and excretion. For this reason, samples will be stored and analysis may be performed on genetic variants involved in the metabolism of tadalafil or finasteride. Analysis may be performed on genetic variants including, but not limited to: genes in the phosphodiesterase pathway, including PDE5; and genes that may play a role in the efficacy or pathways associated with mechanism of action of LY450190, including AR, eNOS, ACE, GNB3, NP-1, and NPR-1. In the event of an unexpected adverse event or the observation of a subject subpopulation that responds differently to LY450190, the samples may be genotyped for markers related to safety. Samples will only be used for investigations related to disease and drugs under study in the context of this clinical trial. They will not be used for broad exploratory genetic analysis 2. Protocol Addendum H6D-CR-LVIW(4), version 23 June 2010: Some countries (including Belgium) participating in Protocol H6D-CR-LVIW have a contraindication for subjects with a history of vision loss due to nonarteritic anterior ischemic optic neuropathy (NAION). Therefore, an exclusion criterion 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. |
|
| 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, OAB, or ED treatments, including alpha blockers, additional 5 ARIs, antimuscarinics, PDE5 inhibitors, or herbal preparations, at any time during the study.
[6] Have not previously taken finasteride or dutasteride at any time prior to screening.
[7] Have not previously taken any other short-acting BPH therapy (including herbal preparations), OAB, or ED therapy for at least 4 weeks prior to the start of the placebo lead-in period, or any investigational BPH therapy with an anticipated prolonged effect, within 6 months of screening.
[8] Have LUTS with a total IPSS ≥13 at the start of the placebo lead-in period.
[9] 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 the start of the placebo lead-in period.
[10] Have prostate enlargement: prostate volume 30 cc or greater on TRUS at screening.
[11] 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. |
|
| E.4 | Principal exclusion criteria |
12] Prostate-specific antigen levels >10.0 ng/mL at screening.
13] Prostate-specific antigen levels ≥4.0 to ≤10.0 ng/mL at screening, if prostate malignancy has not been ruled out to the satisfaction of an urologist.
14] Bladder postvoid residual volume ≥300 mL by ultrasound determination at the start of the placebo lead-in period.
15] 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]Urologic malignancy or trauma.
16] Lower urinary tract instrumentation within 30 days of screening.
17] History of urinary retention or bladder stones within 6 months of screening
18] History of urethral obstruction due to stricture, valves, sclerosis, or tumor
19] Clinical evidence of any of the following bladder conditions:[a] Mullerian duct cysts [b] Atonic, decompensated, hypocontractile bladder [c] Detrusor-sphinctor dyssynergia [d] Intravesical obstruction [e] Interstitial cystitis
20] Clinical evidence of any of the following urinary tract conditions at screening: [a] Urinary tract infection [b] Urinary tract inflammation [c] Current antibiotic therapy for urinary tract infection. [d] Clinically significant microscopic hematuria
21] Clinical evidence of prostate cancer
22] Current neurologic disease or condition associated with neurogenic bladder
23] History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance of <30 mL/minute at screening, as calculated by the central laboratory using the Cockroft-Gault formula
24] Clinical evidence of severe hepatic impairment at screening.
25] 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. [c] Unstable angina within 90 days of screening [d] Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention
26] History of any of the following coronary conditions within 90 days of screening: [a] Myocardial infarction [b] Coronary artery bypass graft surgery [c] Percutaneous coronary intervention
27] Any evidence of moderate to severe heart failure within 6 months of screening 28] Systolic blood pressure >160 or <90 mmHg, or diastolic blood pressure >100 or <50 mmHg at screening (if stress is suspected, retest under basal conditions), or malignant hypertension
29] Scheduled or planned surgery (or any procedure requiring general, spinal, or epidural anesthesia) during the course of the study.
30] History of significant central nervous system injuries within 6 months of screening
31] History of drug, alcohol, or substance abuse within 6 months of screening.
32] Any condition that would interfere with the subject’s 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
33] Current treatment with nitrates, androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone agonists/antagonists, anabolic steroids, antidiuretic hormone, atypical antipsychotics, cancer chemotherapy, serotonin norepinephrine reuptake inhibitors, or tricyclic antidepressants
34] Chronic use or intermittent use of cholinergics, anticholinergics, antimuscarinics, antihistamines, decongestants, sympathomimetics, or phenothiazines
35] Current systemic treatment with any of the following: [a] Potent cytochrome P450 3A4 inhibitors [b] Cytochrome P450 3A4 inducers
36] Glycosylated hemoglobin >9% at screening.
37] Known or suspected hypersensitivity to tadalafil or any other PDE5 inhibitor, finasteride, or any study drug components.
38] Are investigator site personnel directly affiliated with this study and/or their immediate families
39] Are Lilly employees
40] 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, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
41] Have previously completed or withdrawn from this study or any other study investigating tadalafil
42] Are currently in or are planning to be in a sexual relationship with a pregnant female or are currently in a relationship where either partner is actively trying to conceive
43] Are currently in a sexual relationship with a female of child-bearing capacity where no form of birth control is being used
44] History of loss of vision in 1 eye because of NAION, regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy measure is the change in total International Prostate Symptom Score (IPSS) from baseline to 12 weeks of treatment |
|
| 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 | Yes |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 29 |
| 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 |
|
| 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
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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