E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Erectile Dysfunction (ED) |
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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 | 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 |
The primary objective of this study is to compare the efficacy and safety of vardenafil ODT 10 mg (PRN) after 12 weeks of treatment or LOCF with placebo in a general population of men with erectile dysfunction. In this study, 50% of the men on active treatment have to be 65 years-of-age or older. Primary efficacy variables are: - IIEF-EF Domain score at visit 4 (week 12) or LOCF - SEP 2 (success rates of penetration) and SEP 3 (maintenance of erection) at visit 4 (week 12) overall (co-primary variable)
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E.2.2 | Secondary objectives of the trial |
Secondary efficacy variables include: - Percentage of subjects achieving “back to normal” erectile function (IIEF-EF >= 26) at visit 4 (week 12) or LOCF; - All diary questions other than SEP 2 and 3 concerning erectile function administered over the entire treatment period; -Number of sexual attemps under medication till first successful attempt (SEP 3) - Treatment Satisfaction Scale (TSS) to be administered at the randomization visit and the final visit (or at Premature Discontinuation). - A Global Assessment Question (GAQ) concerning the overall effect on erectile function to be administered at the final visit only.
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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 |
24 Subjects will have PK- pharmacokinetic evaluations done at special selected sites. Details are in the protocol that also describes the main study, no additional documentation. |
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E.3 | Principal inclusion criteria |
1) Males 18 years-of-age or older. 2) Stable, heterosexual relationship for at least 6 months. 3) A history of erectile dysfunction (ED) for at least 6 months, defined as “the inability to achieve and maintain an erection of the penis sufficient to complete satisfactory sexual intercourse” by the NIH Consensus Development Panel on Impotence.1 4) The subject must make at least four attempts at sexual intercourse on four separate days during the untreated baseline period (according to the answer to the following question in the Subject Diary: “Was sexual activity initiated with the intention of intercourse?”) (to be fulfilled at visit 2). 5) At least 50% of attempts at sexual intercourse during the untreated baseline period must be unsuccessful, according to the following questions from the Subject Diary (at least one question should be answered with a “No”): a)“Were you able to achieve at least some erection (some enlargement of the penis)?” b)“Were you able to insert your penis in your partner’s vagina?” c)”Did your erection last long enough for you to have successful intercourse?” (to be fulfilled at visit 2). 6) Subjects highly motivated to obtain treatment for erectile dysfunction. 7) Documented, dated, written informed consent.
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E.4 | Principal exclusion criteria |
1) Any underlying cardiovascular condition, including unstable angina pectoris that would preclude sexual activity according to the NIH consensus report.1 2) History of myocardial infarction, stroke or life-threatening arrhythmia within 6 months prior to visit 1 (= screening). 3) Uncontrolled atrial fibrillation / flutter at screening (defined as ventricular response rate ≥ 100 bpm). 4) Bleeding disorder. 5) History of surgical prostatectomy (Note: Subjects with a history of transurethral resection of prostrate (TURP), cryosurgery, cryotherapy or cryoablation can be included in the study). 6) Hereditary degenerative retinal disorders such as retinitis pigmentosa. 7) History of loss of vision because of NAION, temporary or permanent loss of vision, including unilateral loss of vision. 8) Presence of penile anatomical abnormalities (e.g. penile fibrosis or Peyronie’s disease) which, in the investigator’s opinion, would significantly impair sexual performance. 9) Subjects who have been confirmed with phenylketonuria (PKU). 10) Primary hypoactive sexual desire. 11) Spinal cord injury. 12) Severe chronic or acute liver disease, history of moderate (Child-Pugh B), or severe (Child-Pugh C) hepatic impairment. 13) Clinically significant chronic hematological disease which may lead to priapism such as sickle cell anemia, multiple myeloma, and leukemia. 14) Active peptic ulceration. 15) 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). 16) History of syncope within the last 6 months prior to the entry into the study. 17) History of malignancy within the past 5 years (other than squamous or basal cell skin cancer). 18) History of positive test for Hepatitis B surface antigen (HbsAg) or Hepatitis C. 19) Symptomatic postural hypotension within 6 months of Visit 1. 20) 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. 21) History of congenital QT prolongation. 4.2.2.2 Concomitant medication 1) Subjects who are taking nitrates or nitric oxide donors. 2) Subjects who are exposed to androgens irrespective of their mode of administration. 3) Subjects who are taking anti-androgens, except 5alpha-reductase inhibitors. 4) Subjects who are taking alpha-blockers. 5) Subjects who are taking the following potent inhibitors of cytochrome P450 3A4: HIV protease inhibitors such as ritonavir or indinavir, the anti-mycotic agents itraconazole or ketoconazole (topical forms are allowed), and the macrolide antibiotics clarithromycin and erythromycin. 6) Subjects who have received any investigational drug (including placebo) within 30 days of Visit 1. 7) Use of any treatment for ED within 7 days of Visit 1 or during the study including oral medications, vacuum devices, constrictive devices, injections, urethral suppositories, gels, any over-the-counter or non-prescription medications, and products purchased via the internet. 4.2.2.3 Abnormal laboratory values 1) Subjects who have a total serum testosterone level of more than 25% below the lower limit of normal according to the range of the testing laboratory. 2) Subjects with a serum creatinine clearance (calculated) < 30.0 mg/min. 3) Elevation of AST and/or ALT > 3 times the upper limit of normal. 4.2.2.4 Other exclusion criteria 1) Subjects unwilling to cease use of any treatment for ED during the study, including oral medications, vacuum devices, constrictive devices, injections, urethral suppositories, gels, any over-the-counter or non-prescription medications, and products purchased via the internet. 2) Subjects with known hypersensitivity to vardenafil, BAY 38-9456 (also known as SB-782528) or any component of the investigational medication. 3) Subjects who are illiterate or unable to understand the questionnaires or the Subject Diary. 4) Subjects who are unwilling or unable to complete the Subject Diary. 5) Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedule or study procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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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The end of the study is defined as the Last Patient Last Visit date. This is the date of the last follow-up telephone call after visit 4 (or visit 5 for PK subjects). |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |