| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild and/or moderate erectile dysfunction (ED) |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| 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 |
| To assess the efficacy of three GTN gel doses (0.3, 0.6, 0.9mg) applied to the glans of the penis in treating mild and/or moderate erectile dysfunction (ED) relative to placebo. |
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| E.2.2 | Secondary objectives of the trial |
to determine the safety and tolerability of three GTN gel doses (0.3, 0.6 and 0.9 mg) applied to the glans of the penis in subjects with mild and/or moderate erectile dysfunction.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Aged between 18 and 65 years of age.
2. Males with mild and/or moderate ED for more than 6 months, according to the NIH Consensus Statement (inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance).
3. IIEF-EF score in the range of 11 to 25 inclusive, denoting mild and/or moderate ED at screening.
4. The subject must make at least four attempts at sexual intercourse (according to the question in the screening phase diary: “Was sexual activity initiated with the intention of intercourse?”) on four separate days during the 4 weeks of the treatment-free run-in period.
5. 50% or more of the attempts during the 4 week run-in period must be unsuccessful, according to the following questions from the screening phase diary [at least one question should be answered "No"]: “Were you able to achieve at least some erection (some enlargement of the penis)?”, “Were you able to insert your penis into your partner’s vagina?” and “Did your erection last long enough for you to have successful intercourse?“.
6. Stable monogamous heterosexual relationship for more than 6 months prior to screening.
7. Reproduction and Contraception (at least one of the following criteria must apply):
a) Sterile male subjects documented by bilateral vasectomy, bilateral orchiectomy, or azoospermia prior to the subject’s entry into the study, OR
b) Female partners of study subjects that are of child bearing potential that are practicing a satisfactory method of contraception for at least 3 months prior to screening:
- oral contraceptive, either combined or progestogen alone OR
- injectable progestogen OR
- implants of levonorgestrel OR
- estrogenic vaginal ring OR
- percutaneous contraceptive patches OR
- intrauterine device (IUD) or intrauterine system (IUS) OR
- double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] plus spermicidal agent [foam, gel, film, cream, suppository]).
Additionally, a negative result to a human chorionic gonadotropin (HCG) urine pregnancy test performed at home must be obtained by the female partner of the study subject at the beginning of each treatment phase, OR
c) Female partners of study subjects that are post-menopausal, as defined as >45 years old, and greater than 1 year since their last menstrual period, in the absence of hormone replacement therapy, OR
d) Female partners who are medically proven to be infertile even in the absence of contraception.
8. Understands and is willing, able and likely to comply with all study procedures and restrictions.
9. Subject and his partner demonstrate understanding of the study and willingness to participate as evidenced by voluntary written informed consents and have received signed and dated copies of the informed consent forms.
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| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Previous or Current Medical Conditions
1. 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.
2. Presence of penile anatomical abnormalities (e.g., phimosis, penile fibrosis or Peyronie’s disease) that, in the opinion of the Investigator, would significantly impair sexual performance.
3. Primary hypoactive sexual desire.
4. Spinal cord injury.
5. History of any pelvic surgery (prostatectomy, colon surgery).
6. A history of priapism.
7. Clinically significant chronic haematological disease which may lead to priapism such as sickle cell anaemia, multiple myeloma or leukaemia.
8. Any underlying cardiovascular condition including unstable angina pectoris that would preclude sexual activity.
9. History of myocardial infarction, stroke, hypertrophic obstructive cardiomyopathy, aortic stenosis, cardiac tamponade, constrictive pericarditis, mitral stenosis or any life-threatening arrhythmia within the prior 6 months.
10. Uncontrolled atrial fibrillation/flutter (ventricular response rate 100 bpm) at the screening visit (Visit 1).
11. Resting hypotension (a resting systolic blood pressure of <90 mmHg) or hypertension (a resting systolic blood pressure >170 mmHg or a resting diastolic blood pressure >110 mmHg).
12. Symptomatic postural hypotension within 6 months of Screening.
13. History of malignancy within the past 5 years.
14. Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
15. Male subjects whose female partner is breastfeeding or plans to breastfeed at any time during the study.
Concomitant Medications
16. Subjects who are taking nitrates or nitric oxide donors.
17. Subjects who are taking anti-androgens.
18. Use of any treatment for ED in the past, including but not limited to oral ED medications, vacuum devices, intracavernosal injections, penile prosthesis, urethral suppositories.
19. Use of phosphodiesterase-5 inhibitors such as sildenafil, vardenafil or tadalafil is strictly prohibited during the course of the study.
Abnormal Laboratory Values
20. Subjects who have a serum total testosterone level below the lower limit of normal according to the range of the testing laboratory.
Other exclusion criteria
21. Subjects who are illiterate or unable to understand the questionnaires or the Subject Diary.
22. Subjects who are unwilling or unable to complete the Subject Diary.
23. Unwillingness of the subject to make 4 attempts at sexual intercourse on four separate days during the treatment-free baseline period.
24. Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedule of study procedures.
25. Inability to satisfactorily use the Del Pouch® to apply study medication.
26. Clinical Study/Experimental Medication
a. Participation in another clinical study or receipt of an investigational drug (including placebo) less than 3 months prior to the screening visit (Visit 1).
b. Previous participation in this study.
27. An employee or a close family member of either FMD or SSL.
28. An employee of the study site or a close family member of an employee at the study site.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
A successful outcome will have been deemed to occur if 0.3, 0.6 or 0.9 mg GTN gel treatment results in a statistically significant improvement over placebo treatment with regard to Sexual Encounter Profile SEP3 score.
The primary endpoint in assessing efficacy will be:
• Success rate in SEP3 (Did your erection last long enough for you to have successful intercourse?).
Success rates will be calculated first at the per-subject level and then averaged at the group level (i.e. mean success rate). In instances where a subject makes more than one sexual attempt per dose, a dose will be considered successful if one or more of the attempts are successful.
Analysis of Covariance (ANCOVA) will be used to analyse the proportion of successes for the SEP3 endpoint. Success rates for SEP3 during the 4 week run-in period will be used as baseline SEP3, and will be adjusted for in the analysis. Additionally, factors for treatment, study centre (or country), study period and subject (as a random effect) will be included in the model. Difference in least square means for placebo versus active doses, together with 95% confidence intervals and p-values will be presented.
If the assumptions of normality or variance heterogeneity are not met, an appropriate non-parametric method will be used instead.
The following specific null hypotheses will be tested for SEP3:
H01: There is no difference in scores for MED2005 0.3mg compared with placebo.
H02: There is no difference in scores for MED2005 0.6mg compared with placebo.
H03: There is no difference in scores for MED2005 0.9 mg compared with placebo.
The comparisons will be carried out at the 5% level of statistical significance. As the primary parameter has been specified and the objective is to identify a single dose level for further investigation, an adjustment to protect the overall experiment-wise Type I error rate has not been planned.
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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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.1.6 | Cross over | Yes |
| 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.8.3 |
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 | 7 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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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| Last visit of the last subject. |
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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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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