E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Inability to achieve or maintain erection sufficient for satisfactory sexual performance |
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E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061461 |
E.1.2 | Term | Erectile dysfunction |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015116 |
E.1.2 | Term | Erectile disturbance |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025503 |
E.1.2 | Term | Male erectile disorder |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052003 |
E.1.2 | Term | Erectile dysfunction NOS |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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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 demonstrate the efficacy of MED2005 versus placebo in male subjects clinically diagnosed with ED using the EF domain of the IIEF, the Sexual Encounter Profile (SEP) Question 2 and the SEP Question 3. The primary objective will be addressed by estimating the following estimand: difference between treatment policies (each MED2005 dose versus placebo) in all subjects who met the study inclusion/exclusion criteria and who were randomised and attempted intercourse post-randomisation at least once, assessed via the change compared to baseline in EF [IIEF EF], the ability to achieve vaginal penetration [SEP Question 2] and the ability to have successful intercourse [SEP Question 3] over 12 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of MED2005 in male subjects using the Self Esteem And Relationship (SEAR) questionnaire for men and women, the Global Assessment Questionnaire (GAQ), the additional domains of the IIEF, the Patient Global Impression of Severity (PGI S), the Patient Global Impression of Change (PGI C) as well as subjective measures of the time of onset and duration of action (erection) and erection hardness and additional questions on usage and application of MED2005 - To evaluate the long-term (up to 12 months) efficacy of MED2005 - To evaluate the safety of MED2005 using AEs and standard physico-chemical assessments
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 Acceptable methods of contraception are listed below; it should be noted that condoms, femidoms, diaphragms, caps or hormone rings are not permitted as a form of contraception in this study: Surgical sterilisation of the male partner (vasectomy with documentation of azoospermia if possible) The female partner has undergone documented tubal ligation (female sterilisation) The female partner uses combined hormone injectables The female partner uses medically prescribed hormonal implants The female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS) The female partner uses combined oral contraceptives The female partner uses progesterone only contraceptives The female partner uses combined hormonal patches Other than for male/female sterilisation, if any of these above listed methods are being used then their effectiveness must be determined by the PI or their delegate, taking into consideration the compliance and tolerance of the female partner with this method of contraception. 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 Acceptable methods of contraception are listed below; it should be noted that condoms, femidoms, diaphragms, caps or hormone rings are not permitted as a form of contraception in this study: - Surgical sterilisation of the male partner (vasectomy with documentation of azoospermia if possible) - The female partner has undergone documented tubal ligation (female sterilisation) - The female partner uses combined hormone injectables - The female partner uses medically prescribed hormonal implants - The female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS) - The female partner uses combined oral contraceptives - The female partner uses progesterone only contraceptives - The female partner uses combined hormonal patches Other than for male/female sterilisation, if any of these above listed methods are being used then their effectiveness must be determined by the PI or their delegate, taking into consideration the compliance and tolerance of the female partner with this method of contraception.
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E.4 | Principal 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; at PI's 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 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 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 or from the alcohol breath test at screening 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 HBsAG, hepatitis C antibody, and 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 4 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) Exclusion criteria for open-label extension: 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 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. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The change from baseline of the average of the Week 4, Week 8 and Week 12 IIEF EF domain scores 2. The change in percentage of sexual intercourse attempts in which subjects were able to insert their penis into their partner’s vagina (SEP Question 2) between baseline and the 12 week treatment period 3. The change in percentage of sexual intercourse attempts in which subjects were able to maintain an erection of sufficient duration to have successful intercourse (SEP Question 3) between baseline and the 12 week treatment period
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Week 4, Week 8 and Week 12 2. Week 12 3. Week 12
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E.5.2 | Secondary end point(s) |
- The SEAR questionnaire, completed by the male subjects and their female partners - Global assessment via completion of the GAQ, completed by the male subjects and their female partners - The additional domains of the IIEF questionnaire, completed by the male subjects - The other SEP questions (Questions 1, 4 and 5), completed by the male subjects - The SEP questions completed by the female partners - The PGI-S scale, completed by the male subjects - The PGI-C scale, completed by the male subjects - Time of onset and duration of action (erection) and erection hardness, completed by the male subjects and their female partners - Questions on the usage and application of the gels, completed by the male subjects
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As all secondary end points are associated with study questionnaires and scales, timepoints for evaluation of these end points will be visits when corresponding questionnaires and scales will be completed (please refer to Table 2 in section 8.1 of the Study Protocol). |
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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 | Yes |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 | No |
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 |
Bulgaria |
Czech Republic |
Georgia |
Hungary |
Latvia |
Poland |
Russian Federation |
Slovakia |
Ukraine |
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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 | 2 |
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 |