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

A Phase III, Dose Ranging, Multi-centre, Randomised, Double Blind, Placebo Controlled, Home Use, Parallel Group Clinical Trial of Topically-applied Glyceryl Trinitrate for the Treatment of Erectile Dysfunction, With an Open Label Extension

To demonstrate the efficacy of various doses of MED2005 versus placebo in male patients with clinically diagnosed erectile dysfunction, and to evaluate the long-term efficacy and safety (12 months) of MED2005.

A phase III, dose-ranging, multi-centre, randomised, double-blind, placebo controlled , home-use, parallel group clinical trial of topically applied glyceryl trinitrate for the treatment of erectile dysfunction with an open label extension

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 NIH Consensus Statement ('the inability to achieve or maintain penile erection sufficient for satisfactory sexual performance at least once')
3. Subject answers 'yes' to the question regarding the presence of residual EF over the past 3 months: 'At home over the past 3 months, have you experienced at least some growth of your penis in response to: (1) mechanical stimulation by yourself or your partner, or (2) visual stimulation?'
4. Subject has been involved in a continuous heterosexual relationship for at least 6 months 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 of first sexual intercourse attempt during the screening period until the last administration of study treatment, then the couple must have been using a medically acceptable 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 drug administration. Subjects who are or wish to become pregnant will not be included in the study.
7. Subject and his female partner are capable of understanding and complying with the requirements of the protocol and must have signed the ICF prior to participation in any 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 the following inclusion criteria at the follow-up visit of the double-blind phase (Visit 6):

1. Subject and his female partner complete the double-blind phase
2. Subject and his female partner were compliant to study procedures during the double blind phase
3. Documented written informed consent from both subject and his female partner
4. If the male subject's female partner is of childbearing potential from the time of first sexual intercourse attempt during the screening period until the last administration of study treatment, then the couple must have been using a medically acceptable 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 drug administration. Subjects who are or wish to become pregnant will not be included in the study.

Exclusion Criteria:

1. Any significant or serious cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological or psychiatric disease which, in the opinion of the PI, renders the subject unfit to take part in the study
2. Subject has any history of an unstable medical or psychiatric condition or using any medication that, in the opinion of the PI, is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study Certain concomitant medications; e.g. other vasodilators, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, beta blockers, diuretics, anti hypertensives, tricyclic anti depressants and major tranquillisers, as well as the consumption 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 or their delegate at screening or during the study
4. Any presence of chronic indwelling urethral catheterisation or penile anatomical abnormalities (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 to other organic nitrates
11. Concomitant treatment with sildenafil citrate, tadalafil, vardenafil and other PDE 5 inhibitors
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 in such states could produce severe hypotension or shock
18. Increased intracranial pressure (e.g. head trauma or cerebral haemorrhage) or inadequate 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 to become 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 result from the urine drug screen or alcohol breath tests at screening will mean the subject will be excluded from the study). In the instance that a subject is using medication which 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 surface antigen (HBsAG), hepatitis C antibody, and human immunodeficiency virus (HIV)
28. Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission
29. Subjects unwilling to cease use of vacuum devices, intracavernosal injections, PDE-5s or 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 attempts at 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 language in which the questionnaires are available
34. Subject has received any investigational product during the 90 days prior to dosing for 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 the time of penetration)

Subjects are prohibited from participating in the open-label extension phase of the study if they meet any of the following exclusion criteria at the follow-up visit of the double-blind phase (Visit 6):

1. Subsequent to recruitment into the double-blind phase of the study, the development of any significant or serious cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological or psychiatric disease which, in the opinion of the PI, renders the subject unfit to continue in the open-label extension phase of the study

2. Subject using any medication that, in the opinion of the PI, is likely to affect the subject'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 the open-label extension phase. Certain concomitant medications; e.g. other vasodilators, calcium channel blockers, ACE inhibitors, beta blockers, diuretics, anti hypertensives, tricyclic anti depressants and major tranquillisers, as well as the consumption 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 or their delegate at the start of the open-label extension phase

4. Subsequent to recruitment into the double-blind phase of the study, the development of postural hypotension, hypotension or uncorrected hypovolaemia, increased intracranial pressure or inadequate cerebral circulation, any clinically significant vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at Visit 6 prior to recruitment to the open-label phase