E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Erectile dysfunction following Bilateral Nerve-Sparing Radical Prostatectomy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050756 |
E.1.2 | Term | Radical prostatectomy |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
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 5 mg once a day (OAD) and tadalafil 20 mg on demand (PRN), compared with placebo, when taken orally over 9 months, in improving unassisted erectile function in men who develop erectile dysfunction after bilateral nerve-sparing radical prostatectomy. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of tadalafil 5 mg OaD on drug-assisted erectile function when administered to all subjects at the end of the 3-month, open-label period. - To evaluate the efficacy of tadalafil compared with placebo on drug-assisted erectile function at the end of the 9-month, placebo-controlled period. - To evaluate the efficacy of tadalafil compared with placebo on unassisted erectile function at the end of the washout period. - To evaluate the effect of tadalafil compared with placebo on penile length and girth. - To evaluate the effect of tadalafil compared with placebo on spontaneous morning erections. - To evaluate subjects’ satisfaction with tadalafil compared with placebo. - To evaluate subjects’ and partners’ quality of life following tadalafil compared with placebo. - To evaluate psychosocial outcomes of tadalafil compared with placebo. - To assess the safety of tadalafil 5 mg OaD and tadalafil 20 mg PRN, compared with placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male and aged >=18 years at Visit 1, and <65 years at time of BNSRP. -Able to read, understand and provide signed informed consent. -Have no history of ED at Visit 1, and a normal preoperative erectile function score, without the use of therapy or devices for the improvement of erections. -Are scheduled to undergo bilateral NSRP surgery for organ-confined, non-metastatic prostate cancer up to approximately 6 weeks after Visit 1. -Have an interest in resuming sexual activity as soon as possible after surgery and anticipate having the same adult female sexual partner during the study. -Have a historical total PSA level <10 ng/mL prior to Visit 1. -Have a clinical stage of prostate cancer of T1c to T2c. -Have a biopsy Gleason score <=7. -Agree not to use any other treatment for ED, including herbal and over-the-counter (OTC) medications, during the study. -Agree to participate in recording responses to questionnaires and other instruments used in this study. Post-Surgical Inclusion Criteria -Have an operating report with confirmation of bilateral nerve-sparing during the prostatectomy procedure, as determined by a total (composite) score of 3 or less. -Have Grade 0-3 Residual Erectile Function, as measured at Visit 4. -Have developed ED after surgery, as measured at Visit 4. -Have a final pathological stage that does not require the initiation of adjuvant therapy for prostate cancer. |
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E.4 | Principal exclusion criteria |
At Visit 1: -Have a history of ED, with or without treatment. -Have a history of prostatic surgery or prostatic physical treatments. -Have a history of penile implant. -Have a history of drug, alcohol or substance abuse within the previous 6 month. -Have a history of galactose intolerance, lapp lactase deficiency, or glucose-galactose malabsorption. At Visit 1 or Visit 4: -Have received previous or current treatment with tadalafil or any other PDE5 inhibitor. -Require treatment with doxazosin or nitrates after Visit 4, or have received treatment with cancer chemotherapy, luteinising hormone-releasing hormone (LH-RH) analogues, LH-RH antagonists, or anti-androgens. -Have undergone, or plan to undergo, radiation or hormonal therapy for prostate cancer. -Have ED post-BNSRP caused by untreated endocrine disease. -Have a clinically significant penile deformity. -Have a communicable skin or sexually transmitted disease, or have any rash or lesions on the penis or surrounding area. -Exhibit evidence of clinically significant renal insufficiency. -Exhibit clinical evidence of severe hepatic impairment. -Have a history of diabetes mellitus. -Present with chronic stable angina treated with long-acting nitrates, or with chronic stable angina requiring short-acting nitrates in the previous 90 days, or with angina occurring during sexual intercourse in the previous 6 months. -Have met the criteria for unstable angina within the previous 6 months, or have a history of myocardial infarction or coronary artery bypass graft surgery within the previous 90 days, or percutaneous coronary intervention within the previous 90 days. -Have any supraventricular arrhythmia with an uncontrolled ventricular response (mean heart rate >100 bpm) at rest, or have any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 bpm for >=30 seconds), or use an automatic internal cardioverter-defibrillator. -Have a history of sudden cardiac arrest. -Exhibit any evidence of congestive heart failure (New York Heart Association [NYHA] Class II or above) within the previous 6 months. -Have a history of new significant cardiac conduction defect within the previous 90 days. -Exhibit systolic BP >170 or <90 mmHg or diastolic BP >100 or <50 mmHg (if stress is suspected, retest under basal conditions), or have a history of malignant hypertension. -Have a history of significant central nervous system injuries within the previous 6 months. -Have a history of loss of vision in one eye because of nonarteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. -Have a history of human immunodeficiency virus (HIV) infection. -Have any condition that, in the opinion of the investigator, would interfere with the subject’s ability to provide informed consent or comply with study instructions, would place the subject at increased risk, or might confound the interpretation of the study results. -Are investigator site personnel directly affiliated with this study and/or their immediate family. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. -Are Lilly employees. -Are currently enrolled in, or have 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/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. -Have previously completed or withdrawn from this study or any other study investigating tadalafil. Exclusion Criteria Post-Surgery -Require radiotherapy, hormonal or adjuvant anti-cancer therapy for prostate cancer, according to the investigator’s clinical judgment and as assessed by clinical and PSA findings. -Require further surgery due to haemorrhage, or have any evidence of local recurrence or occurrence of any metastasis. -Urethral catheter expected to be in place for >3 weeks due to anastomotic insufficiency or fistula. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of subjects with a score of >=22 in the IIEF-EF Domain after 6 week drug-free washout. |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
The 9 month randomised treatment period is followed by a 3-month open label treatment period. |
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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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
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 | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |