| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Classification code | 10061461 | |
| 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 objective of this study is to compare the efficacy and safety of two modes of vardenafil therapy versus placebo to treat erectile dysfunction, starting within 14 days following bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP). Specifically, the primary objective is to determine whether early, NIGHTLY dosing with vardenafil significantly improves recovery of erectile function after surgery as compared to placebo, and whether early PRN dosing with vardenafil also improves recovery of function as compared to placebo | |
| E.2.2 | Secondary objectives of the trial | | To assess whether early dosing of either NIGHTLY or PRN vardenafil over 9 months, followed by 2 months of withdrawal, increases efficacy of subsequent PRN use significantly better than placebo | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | At Screening:
Males 18-64 years of age
Scheduled to undergo bilateral nerve-sparing radical retropubic BNSRRP, as selected according to the investigator’s usual clinical practice
Surgery scheduled within about 1 month of screening (Visit 1)
Expressed an interest in resuming sexual activity as soon as possible after prostatectomy
Heterosexual relationship.
No pre-operative erectile dysfunction: International Index of Erectile Function (IIEF) Erectile Function Domain Score score EF domain ≥26 at screening (Visit 1) without any therapy/devices for improvement of erections. No previous use of any therapy/devices for erectile dysfunction
Historical total prostate specific antigen (PSA) <10 ng/mL
Gleason Tumor Score ≤ 7 on biopsy
No perforation of the prostate capsule by tumor: Clinical stage pre-operatively T1c to T2a/2b
Documented, signed and dated written Informed Consent
At Randomization:
Bilateral nerve-sparing during the retropubic prostatectomy documented on the operating report
BNSRRP occurred within approximately 1 month post screening (Visit 1)
No perforation of the prostate capsule by tumor: No positive tumor margins confirmed after surgery: ≤T2 stage on pathology report from the surgery
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| E.4 | Principal exclusion criteria | At Screening:
A)Previous or Current Medical Conditions:
Any unstable medical, psychiatric, or substance abuse disorder that, in the opinion of the investigator, is likely to affect the subject's ability to complete the study or precludes the subject’s participation in the study
Presence of penile anatomical abnormalities (e.g. penile fibrosis or Peyronie’s disease) in the opinion of the Investigator would significantly impair sexual performance
Primary hypoactive sexual desire
Spinal cord injury
Hereditary degenerative retinal disorders such as retinitis pigmentosa
History of positive test for Hepatitis B surface antigen (HbsAg) or Hepatitis C
Severe chronic or acute liver disease, including history of moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
Clinically significant chronic hematological disease which may lead to priapism such as sickle cell anemia, multiple myeloma or leukemia
Bleeding disorder
Significant active peptic ulceration
Any underlying cardiovascular condition including unstable angina pectoris that would preclude sexual activity
History of myocardial infarction, stroke, or life-threatening arrhythmia within the prior 6 months
Uncontrolled atrial fibrillation/flutter at screening (ventricular response rate > 100 bpm)
Resting hypotension (a resting systolic blood pressure of <90 mm Hg) or hypertension (a resting systolic blood pressure >170 mm Hg or a resting diastolic blood pressure >110 mm Hg)
Symptomatic postural hypotension within 6 months of Visit 1
History of malignancy within the past 5 years (other than prostate cancer or squamous or basal cell skin cancer)
Life expectancy <3 years
Clinical diagnosis of significant untreated sleep apnea or working night shifts (e.g. 23:00h to 7:00 h).
Diabetes mellitus: type I, type II with presence of end organ symptomatology (e.g. peripheral neuropathy, nephropathy, retinopathy, amyotrophy)
B) Concomitant Medication:
Nitrates or nitric oxide donors
Oral or injectable androgens
Anti-androgens
Any of the following potent inhibitors of cytochrome P- 450 3A4: HIV protease inhibitors such as ritonavir or indinavir; anti-mycotic agents itraconazole and ketoconazole (topical forms are allowed); or erythromycin
Any investigational drug (including placebo) within 30 days of Visit 1
Any treatment for ED historically or during the study, including oral medications, vacuum devices, constrictive devices, injections or urethral suppositories
Alpha blockers
C) Abnormal Laboratory Values:
Serum total testosterone level >25% below the lower limit of normal (according to the range of the testing laboratory).
Serum creatinine > 3.0 mg/dL.
Elevation of AST and/or ALT >3X the ULN
D) Other Exclusions:
Known hypersensitivity to vardenafil, Bay 38-9456 (also known as SB-782528) or any component of the investigational medication
Illiterate or are unable to understand the questionnaires or subject diary
Unwilling or unable to complete the subject diary or questionnaires
At Randomization:
Residual prostate cancer, or requirement for radiotherapy or ADT
Need for a re-exploration surgery due to hemorrhage
Need for urethral catheter expected to be ≥3 weeks due to anastomotic fistula | |
| E.5 End points |
| E.5.1 | Primary end point(s) | The primary measure of efficacy in this study is:
Percent of subjects with the erectile function domain score of the International Index of Erectile Function (IIEF EF domain score, calculated as the sum of scores from Questions 1-5 and 15) of >22 after 9 months of double-blind treatment plus 1-2 months of single-blind placebo wash-out, using the single blind wash-out last observation carried forward (SB wash-out LOCF) method to account for dropouts. Only observations collected during the 2 month single blind washout period will be included in the SB washout LOCF.
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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 | 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 | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.3 | Single blind | Yes |
| 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 | | 9 months double blind, 2 months single blind placebo,2 months open label PRN active | |
| 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 | Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 | |
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
