Clinical Trial Using Topically Applied Glyceryl Trinitrate (GTN) for the Treatment of Erectile Dysfunction

Inclusion Criteria:

1. Subject is a male aged between 18 and 70 years inclusive, at screening
2. Confirmed clinical diagnosis of ED for more than 3 months according to the NIHConsensus Statement ('the inability to achieve or maintain penile erection sufficientfor satisfactory sexual performance at least once')
3. Subject answers 'yes' to the question regarding the presence of residual EF over thepast 3 months: 'At home over the past 3 months, have you experienced at least somegrowth of your penis in response to: (1) mechanical stimulation by yourself or yourpartner, or (2) visual stimulation?'
4. Subject has been involved in a continuous heterosexual relationship for at least 6months prior to screening
5. Documented written informed consent from both subject and his female partner
6. If the male subject's female partner is of childbearing potential from the time offirst sexual intercourse attempt during the screening period until the lastadministration of study treatment, then the couple must have been using a medicallyacceptable form of contraception for at least 3 months prior to entering the study,and agree to continue such use for at least 1 month after the last study drugadministration. Subjects who are or wish to become pregnant will not be included inthe study.
7. Subject and his female partner are capable of understanding and complying with therequirements of the protocol and must have signed the ICF prior to participation inany study related procedures
8. Low IIEF-EF scores (≤ 25) during the screening period To continue in the open-label extension phase of the study, subjects must meet thefollowing inclusion criteria at the follow-up visit of the double-blind phase (Visit 6):
9. Subject and his female partner complete the double-blind phase
10. Subject and his female partner were compliant to study procedures during the doubleblind phase
11. Documented written informed consent from both subject and his female partner
12. If the male subject's female partner is of childbearing potential from the time offirst sexual intercourse attempt during the screening period until the lastadministration of study treatment, then the couple must have been using a medicallyacceptable form of contraception for at least 3 months prior to entering the study,and agree to continue such use for at least 1 month after the last study drugadministration. Subjects who are or wish to become pregnant will not be included inthe study.

Exclusion Criteria:

1. Any significant or serious cardiovascular, pulmonary, hepatic, renal,gastrointestinal, haematological, endocrinological, metabolic, neurological orpsychiatric disease which, in the opinion of the PI, renders the subject unfit to takepart in the study
2. Subject has any history of an unstable medical or psychiatric condition or using anymedication that, in the opinion of the PI, is likely to affect the subject's abilityto complete the study or precludes the subject's participation in the study Certainconcomitant medications; e.g. other vasodilators, calcium channel blockers,angiotensin converting enzyme (ACE) inhibitors, beta blockers, diuretics, antihypertensives, tricyclic anti depressants and major tranquillisers, as well as theconsumption of alcohol, may potentiate the BP lowering effects of MED2005; therefore,the PI must consider this carefully and include subjects at their discretion
3. Any presence of a symptomatic, active urinary tract infection diagnosed by the PI ortheir delegate at screening or during the study
4. Any presence of chronic indwelling urethral catheterisation or penile anatomicalabnormalities (e.g. penile fibrosis) that would significantly impair EF
5. Any history of operations for Peyronie's disease
6. Primary hypoactive sexual desire or any history of hypogonadism
7. Any history of radical prostatectomy
8. Any history of severe/uncontrolled diabetes
9. Subjects taking two or more anti hypertensives for the treatment of BP
10. Hypersensitivity to GTN or to any of the excipients, or idiosyncratic reactions toother organic nitrates
11. Concomitant treatment with sildenafil citrate, tadalafil, vardenafil and other PDE 5inhibitors
12. Subjects taking Alpha blockers
13. Subjects receiving testosterone pellets
14. Any penile surgery except circumcision
15. Any treatment with acetyl cysteine within 6 months
16. Any treatment with dihydroergotamine within 6 months
17. Postural hypotension, hypotension or uncorrected hypovolaemia, as the use of GTN insuch states could produce severe hypotension or shock
18. Increased intracranial pressure (e.g. head trauma or cerebral haemorrhage) orinadequate cerebral circulation
19. Any history of migraine or recurrent headache
20. Aortic or mitral stenosis
21. Hypertrophic obstructive cardiomyopathy
22. Constrictive pericarditis or pericardial tamponade
23. Closed-angle glaucoma
24. Subjects with nursing partners, known pregnant partners or with partners who wish tobecome pregnant during the course of the study
25. Confirmed positive results from urine drug screen (amphetamines, benzodiazepines,cocaine, cannabinoids, opiates, barbiturates, tricyclic antidepressants and methadone)or from the alcohol breath test at screening (for clarification, any positive resultfrom the urine drug screen or alcohol breath tests at screening will mean the subjectwill be excluded from the study). In the instance that a subject is using medicationwhich may give a positive result, exclusion will be at the PI's discretion
26. Subject has recent (last 12 months) clinical evidence of alcoholism or drug abuse.
27. Subject has a positive screen for hepatitis B, consisting of hepatitis B surfaceantigen (HBsAG), hepatitis C antibody, and human immunodeficiency virus (HIV)
28. Any clinically significant abnormal laboratory, vital signs or other safety findingsas determined by medical history, physical examination or other evaluations conductedat screening or on admission
29. Subjects unwilling to cease use of vacuum devices, intracavernosal injections, PDE-5sor other therapy for ED for the entire course of the study
30. Unwillingness of the subject or their partner to agree to make the required attemptsat sexual intercourse during treatment period
31. Any history of unresponsiveness to PDE 5 treatment or significant side effects,excluding visual disturbances, with PDE 5s
32. Fewer than four attempts at sexual intercourse during the screening period
33. Subjects or their partners who are illiterate or are unable to understand the languagein which the questionnaires are available
34. Subject has received any investigational product during the 90 days prior to dosingfor this study
35. Subject or his partner cannot communicate reliably with the PI
36. Subjects with severe premature ejaculation (little or no control of ejaculation at thetime of penetration) Subjects are prohibited from participating in the open-label extension phase of the studyif they meet any of the following exclusion criteria at the follow-up visit of thedouble-blind phase (Visit 6):
37. Subsequent to recruitment into the double-blind phase of the study, the development ofany significant or serious cardiovascular, pulmonary, hepatic, renal,gastrointestinal, haematological, endocrinological, metabolic, neurological orpsychiatric disease which, in the opinion of the PI, renders the subject unfit tocontinue in the open-label extension phase of the study
38. Subject using any medication that, in the opinion of the PI, is likely to affect thesubject's ability to complete or participate in the open-label phase of the study. NB The concomitant medications listed as exclusion criteria for the study apply to theopen-label extension phase. Certain concomitant medications; e.g. other vasodilators,calcium channel blockers, ACE inhibitors, beta blockers, diuretics, antihypertensives, tricyclic anti depressants and major tranquillisers, as well as theconsumption of alcohol, may potentiate the BP lowering effects of MED2005; therefore,the PI must consider this carefully and include subjects at their discretion
39. Any presence of a symptomatic, active urinary tract infection diagnosed by the PI ortheir delegate at the start of the open-label extension phase
40. Subsequent to recruitment into the double-blind phase of the study, the development ofpostural hypotension, hypotension or uncorrected hypovolaemia, increased intracranialpressure or inadequate cerebral circulation, any clinically significant vital signs orother safety findings as determined by medical history, physical examination or otherevaluations conducted at Visit 6 prior to recruitment to the open-label phase