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
Phase: PHASE3
Conditions: Erectile Dysfunction
Sponsor: Futura Medical Developments Ltd.

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                CONFIDENTIAL 
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Protocol Reference: FM57                                           Version 7.0 dated 27 July 2018 
 
CLINICAL STUDY PROTOCOL 
Sponsor’s Reference Number: FM57 
EudraCT Number: 2017-000960-14 
TITLE: 
A 
Phase 
III, 
dose-ranging, 
multi-centre, 
randomised, 
double-blind, placebo-controlled, home use, parallel group 
clinical trial of topically-applied glyceryl trinitrate (GTN) for the 
treatment of erectile dysfunction (ED) with an open label 
extension 
PHASE: 
Phase III 
DRUG: 
MED2005 
SPONSOR: 
Futura Medical Developments Ltd. 
Surrey Technology Centre 
40 Occam Road 
Guildford 
Surrey, GU2 7YG, UK 
Telephone: +44 (0)1483 685670  
 
Fax: 44 (0)1483 685671 
CHIEF INVESTIGATOR: 
Dr Rupert Mason 
Protocol Version 
and Date: 
Version 7.0 
27 July 2018  
 
 
 
 
 
 
 
Information in this protocol is confidential and should not be disclosed, other than to 
those directly involved in the execution or the ethical/regulatory review of the study, 
without written authorisation from Futura Medical Developments Ltd (hereinafter known 
as FMD). 
 
 
 
 

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                CONFIDENTIAL 
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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
1. 
PROTOCOL APPROVAL SIGNATURES 
 
 
Version 7.0, dated 27 July 2018 
 
Sponsor’s Approval 
 
This protocol has been approved by Futura Medical Developments Ltd. 
Sponsor’s Signatories:  
 
Tim Holland, Clinical Development Director, Futura Medical Developments Ltd 
 
Signature: 
 
Date: 
 
 
 
Consultant Statistician, Dr Paul Terrill, Cytel 
 
Signature: 
 
Date: 
 
 
 
Medical Advisor: 
Dr Rupert Mason, Futura Medical Developments Ltd 
 
Signature: 
 
Date: 
 
 

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                CONFIDENTIAL 
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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
Investigator’s Agreement: 
 
I have read this FMD Protocol No. FM57 
A Phase III, dose-ranging, multi-centre, randomised, double-blind, placebo-controlled, 
home use, parallel group clinical trial of topically-applied glyceryl trinitrate (GTN) for the 
treatment of erectile dysfunction (ED) with an open label extension 
I have fully discussed the objectives of this study and the contents of this protocol with FMD 
(the Sponsor). 
I understand that the information in this protocol is confidential and should not be disclosed, 
other than to those directly involved in the execution or the ethical/regulatory review of the 
study, without written authorisation from FMD. It is, however, permissible to provide information 
to a subject in order to obtain consent. 
I agree to conduct this study according to this protocol and to comply with its requirements, 
subject to ethical and safety considerations and guidelines, and to conduct the study in 
accordance with International Council for Harmonisation (ICH) guidelines on Good Clinical 
Practice (GCP) and with the applicable regulatory requirements. 
I understand that FMD may decide to suspend or prematurely terminate the study at any time 
for whatever reason; such a decision will be communicated to me in writing. Conversely, should 
I decide to withdraw from execution of the study I will communicate my intention immediately 
in writing to FMD. 
Principal Investigator:  
 
Printed 
Name: 
 
 
 
 
Signature: 
 
 
Date: 
 

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                CONFIDENTIAL 
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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
2. 
STUDY PERSONNEL 
Sponsor’s Representative 
Tim Holland 
Clinical Development Director 
Futura Medical Developments Ltd. 
Surrey Technology Centre 
40 Occam Road 
Guildford 
Surrey, GU2 7YG, UK 
Telephone: +44 (0)1483 685670  
Fax: +44 (0)1483 685671 
Email: Tim.Holland@futuramedical.com 
 
Sponsor’s Main Contact 
Tim Holland 
Clinical Development Director 
Futura Medical Developments Ltd. 
Surrey Technology Centre 
40 Occam Road 
Guildford 
Surrey, GU2 7YG, UK 
Telephone: +44 (0)1483 685670  
Fax: +44 (0)1483 685671 
Email: Mirfat.Band@futuramedical.com 
 
Sponsor’s Medical Advisor 
Dr Rupert Mason 
Medical Advisor 
Futura Medical Developments Ltd. 
Surrey Technology Centre 
40 Occam Road 
Guildford 
Surrey, GU2 7YG, UK  
Telephone: +44 (0)1767 627085 
Mobile: +44 (0)7811 195044 
Email: rupertmason48@gmail.com 
 
 
 
For complete study administrative structure, see the relevant Sponsor’s file. Where 
applicable, administrative changes are to be documented in the Sponsor’s file without 
requiring formal protocol amendment. 

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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
3. 
TABLE OF CONTENTS  
1. 
PROTOCOL APPROVAL SIGNATURES .......................................................... 2 
2. 
STUDY PERSONNEL ....................................................................................... 4 
3. 
TABLE OF CONTENTS .................................................................................... 5 
4. 
LIST OF ABBREVIATIONS ............................................................................... 9 
5. 
STUDY SYNOPSIS ........................................................................................ 12 
6. 
INTRODUCTION ............................................................................................ 16 
6.1 
Background ..................................................................................................... 16 
6.2 
Rationale for Conducting Study ....................................................................... 17 
6.3 
Clinical Studies with MED2005 ....................................................................... 17 
6.3.1 
Pharmacokinetics ..................................................................................... 17 
6.3.2 
Pharmacodynamics .................................................................................. 18 
6.3.3 
Efficacy and Safety ................................................................................... 18 
6.4 
Risk-Benefit Evaluation ................................................................................... 19 
6.4.1 
Potential Benefits ...................................................................................... 19 
6.4.2 
Potential Risks .......................................................................................... 19 
6.5 
Conduct of the Study....................................................................................... 19 
7. 
STUDY OBJECTIVES ..................................................................................... 20 
7.1 
Primary Objective ............................................................................................ 20 
7.2 
Secondary Objectives ..................................................................................... 20 
8. 
STUDY DESIGN ............................................................................................. 20 
8.1 
Overall Study Design and Plan ....................................................................... 20 
8.2 
Rationale for Study Design ............................................................................. 28 
8.2.1 
Discussion of Study Design ...................................................................... 28 
8.2.2 
Choice of Subjects .................................................................................... 29 
8.2.3 
Rationale for Study Drug Dose and Schedule ........................................... 29 
8.2.4 
Choice of Route and Rate of Administration ............................................. 30 
8.2.5 
Monitoring and Communication of AEs ..................................................... 30 
8.2.6 
Study Principal Investigator, Site Facilities and Personnel ........................ 30 
8.3 
Stopping Criteria ............................................................................................. 30 
9. 
SELECTION AND WITHDRAWAL OF SUBJECTS ......................................... 31 
9.1 
Number and Source of Subjects to be Studied ................................................ 31 
9.2 
Inclusion Criteria ............................................................................................. 31 
9.3 
Exclusion Criteria ............................................................................................ 33 
9.4 
Subject Restrictions ........................................................................................ 35 
9.5 
Subject Inclusion and Randomisation ............................................................. 35 
9.6 
Withdrawal of Subjects .................................................................................... 36 
9.6.1 
Criteria for Withdrawal from Study Drug .................................................... 36 

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9.6.2 
Criteria for Withdrawal from the Study ...................................................... 36 
9.6.3 
Procedures for Subject Withdrawal ........................................................... 37 
10. 
STUDY AND CONCOMITANT TREATMENTS ............................................... 37 
10.1 
Investigational Medicinal Product .................................................................... 37 
10.2 
Methods of Assigning Subjects to Treatment Groups ...................................... 37 
10.3 
Drug Accountability ......................................................................................... 37 
10.4 
Blinding ........................................................................................................... 38 
10.4.1 Methods for Ensuring Blinding .................................................................. 38 
10.4.2 Methods for Unblinding the Study ............................................................. 38 
10.5 
Prior and Concomitant Medications ................................................................. 38 
10.5.1 Prohibited Medications ............................................................................. 39 
10.6 
Treatment Compliance .................................................................................... 39 
11. 
STUDY ASSESSMENTS AND SCHEDULES ................................................. 39 
11.1 
Schedule of Assessments ............................................................................... 39 
11.1.1 Pre-screening Assessments ..................................................................... 39 
11.1.2 Screening Assessments (Visit 1) .............................................................. 40 
11.1.3 Double-Blind Phase: Treatment Period Assessments ............................... 40 
11.1.4 Double-Blind Phase: Follow-up Assessments (Visit 5 + 7 days [ 2 days]; 
Visit 6) ...................................................................................................... 43 
11.1.5 Open-Label Extension Phase Assessments ............................................. 44 
11.2 
Efficacy Assessments ..................................................................................... 46 
11.2.1 International Index for Erectile Function (IIEF) Questionnaire ................... 46 
11.2.2 Sexual Encounter Profile (SEP) Questionnaire ......................................... 47 
11.2.3 Self-Esteem And Relationship (SEAR) Questionnaire .............................. 47 
11.2.4 Global Assessment Questionnaire (GAQ) ................................................. 47 
11.2.5 Patient Global Impression (PGI) Scales .................................................... 48 
11.2.6 Onset and Duration of Action (Erection) and Erection Hardness 
Questions ................................................................................................. 48 
11.2.7 Usage and Application .............................................................................. 48 
11.3 
Safety Assessments........................................................................................ 49 
11.3.1 Adverse events ......................................................................................... 49 
11.3.2 Physical Examination ................................................................................ 49 
11.3.3 Laboratory Safety Assessments ............................................................... 49 
11.3.4 Vital Signs ................................................................................................ 52 
11.3.5 12-lead ECGs ........................................................................................... 52 
11.4 
Other Assessments ......................................................................................... 53 
11.4.1 Informed Consent ..................................................................................... 53 
11.4.2 Eligibility ................................................................................................... 53 
11.4.3 Medical History ......................................................................................... 53 
11.4.4 Volume of Blood Sampling ........................................................................ 53 
11.4.5 Training .................................................................................................... 53 
12. 
ADVERSE EVENTS........................................................................................ 54 

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12.1 
Adverse Events ............................................................................................... 54 
12.1.1 Definitions ................................................................................................. 54 
12.1.2 Recording of Adverse Events ................................................................... 55 
12.1.3 Assessment of Adverse Events ................................................................ 56 
12.1.4 Reporting of Serious AEs.......................................................................... 57 
12.1.1 Reporting and Follow-Up of Pregnancy .................................................... 58 
13. 
QUALITY ASSURANCE AND QUALITY CONTROL ....................................... 59 
13.1 
Quality Assurance and Quality Control ............................................................ 59 
13.2 
Monitoring ....................................................................................................... 59 
13.3 
Blinded Review Meeting .................................................................................. 59 
14. 
STATISTICAL ANALYSES.............................................................................. 60 
14.1 
Analysis Sets .................................................................................................. 60 
14.2 
Demographic and Baseline Measurements ..................................................... 61 
14.3 
Prior and Concomitant Medication .................................................................. 61 
14.4 
Number of Intercourse Attempts ..................................................................... 61 
14.5 
Efficacy Evaluation .......................................................................................... 62 
14.5.1 Efficacy Measures .................................................................................... 62 
14.5.2 Handling of Missing Values ....................................................................... 62 
14.5.3 Primary Analysis ....................................................................................... 63 
14.5.4 Other Efficacy Variables ........................................................................... 64 
14.6 
Evaluation of Safety ........................................................................................ 65 
14.6.1 Vital Signs ................................................................................................ 65 
14.6.2 Clinical Laboratory Safety Tests ............................................................... 65 
14.6.3 ECGs 65 
14.6.4 Adverse Events ........................................................................................ 65 
14.7 
Sample Size .................................................................................................... 66 
15. 
DATA MANAGEMENT .................................................................................... 66 
15.1 
Case Report Forms ......................................................................................... 67 
16. 
SPONSOR AND INVESTIGATOR RESPONSIBILITIES ................................. 67 
16.1 
Sponsor Responsibilities ................................................................................. 67 
16.1.1 GCP Compliance ...................................................................................... 67 
16.1.2 Regulatory Approval ................................................................................. 67 
16.1.3 Indemnity/liability and Insurance ............................................................... 68 
16.1.4 Protocol Management ............................................................................... 68 
16.1.5 End of Study Notification .......................................................................... 68 
16.1.6 Submission of Summary of Clinical Trial Report to Competent Regulatory 
Authorities of Member States Concerned and ECs ................................... 68 
16.2 
Investigator Responsibilities ............................................................................ 68 
16.2.1 GCP Compliance ...................................................................................... 68 
16.2.2 Protocol Adherence and Investigator Agreement ...................................... 69 
16.2.3 Documentation and Retention of Records ................................................ 69 

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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
16.3 
Ethical Considerations .................................................................................... 69 
16.3.1 Informed Consent ..................................................................................... 69 
16.3.2 Ethics Committee Approval ....................................................................... 69 
16.4 
Confidentiality ................................................................................................. 70 
16.5 
Publication Policy ............................................................................................ 70 
17. 
REFERENCES LIST ....................................................................................... 70 
18. 
APPENDIX 1 ................................................................................................... 73 
18.1 
IIEF Questionnaire .......................................................................................... 73 
18.2 
SEP Questionnaire ......................................................................................... 75 
18.3 
SEAR Questionnaire ....................................................................................... 76 
18.4 
GAQ ................................................................................................................ 77 
18.5 
PGI Scales ...................................................................................................... 78 
18.6 
Onset and Duration of Action (Erection) and Erection Hardness Questions .... 79 
18.7 
 Questions on Usage and Application ............................................................. 80 
LIST OF TABLES 
Table 1 
Schedule of Events ................................................................................... 24 
Table 2 
Schedule of Questionnaires ...................................................................... 28 
Table 3 
Laboratory Safety Variables ...................................................................... 50 
 

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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
4. 
LIST OF ABBREVIATIONS  
Abbreviation 
Explanation 
ABPI  
Association of British Pharmaceutical Industry  
ACE  
Angiotensin Converting Enzyme  
ADR  
Adverse Drug Reaction  
AE  
Adverse Event  
ALP  
Alkaline Phosphatase  
ALT  
Alanine Aminotransferase  
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
AST  
Aspartate Aminotransferase  
BMI  
Body Mass Index  
BP 
Blood Pressure  
CI 
Chief Investigator 
CK 
Creatine Kinase  
Cmax  
Maximum plasma concentration  
CRO 
Clinical Research Organisation  
CRP  
C-reactive Protein  
CSR  
Clinical Study Report  
DHP 
Data Handling Plan 
EC 
Ethics Committee  
ECG  
Electrocardiogram  
eCRF 
electronic Case Report Form  
ED 
Erectile Dysfunction  
EF 
Erectile Function  
ePRO 
electronic Patient-Reported Outcomes 
EU 
European Union  
FAS 
Full Analysis Set  
FMD  
Futura Medical Developments Ltd  
GAQ 
Global Assessment Questionnaire  
GCP  
Good Clinical Practice  
GGT 
Gamma-Glutamyl Transpeptidase 
GMP 
Good Manufacturing Practice  
GTN 
Glyceryl Trinitrate  
HBc 
Hepatitis B Core antibodies 
HbsAG 
Hepatitis B Surface Antigen  

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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
HCV 
Hepatitis C Virus 
HIV  
Human Immunodeficiency Virus  
HR 
Heart Rate  
IB 
Investigator’s Brochure 
ICF  
Informed Consent Form  
ICH 
International Council for Harmonisation  
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IIEF  
International Index for Erectile Function  
IMP 
Investigational Medicinal Product  
IP 
Inorganic Phosphate  
IUD 
Intrauterine Device  
IUS 
Intrauterine System  
IVRS 
Interactive Voice Response System 
IWRS 
Interactive Web Response System 
LDH 
Lactate Dehydrogenase  
LS 
Least-Squares 
MCID 
Minimal Clinically Important Difference 
MedDRA 
Medical Dictionary for Regulatory Activities  
MNAR 
Missing Not At Random 
NIH 
National Institutes of Health 
NO 
Nitric Oxide  
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
OLAS 
Open-Label Analysis Set 
PD 
Pharmacodynamic  
PDE-5 
Phosphodiesterase type 5  
PGE 1 
Prostaglandin E1  
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PI 
Principal Investigator  
PK 
Pharmacokinetic  
PP 
Per Protocol  
PT  
Preferred Term  
QA 
Quality Assurance  
QC 
Quality Control  
QP  
Qualified Person  

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ROC 
Receiver Operating Characteristics 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation  
SE 
Standard Error 
SEAR 
Self-Esteem And Relationship questionnaire 
SEP 
Sexual Encounter Profile  
SOC 
System Organ Class  
SPC  
Summary of Product Characteristics  
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
T1/2 
Terminal elimination half-life  
Tmax 
Time to reach Cmax  
TMF 
ULN 
Trial Master File 
Upper Limit of Normal  
US 
United States  
w/w 
Weight in weight 

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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
5. 
STUDY SYNOPSIS 
Protocol Ref: FM57 
Study Product: MED2005 
Title of the Study: 
A Phase III, dose-ranging, multi-centre, randomised, double-blind, placebo-controlled, home use, parallel group 
clinical trial of topically-applied glyceryl trinitrate (GTN) for the treatment of erectile dysfunction (ED) with an open 
label extension 
Chief Investigator:  
Dr Rupert Mason 
Sites: 
Approximately 50 investigational sites in countries including Poland, Hungary, Czech Republic, Slovakia, 
Georgia, Russia, Ukraine, Bulgaria and Latvia. 
Study Period (planned): 
2018–2020 
Clinical Phase: 
III  
 
Objectives: 
Primary Objective 
 
To demonstrate the efficacy of MED2005 versus placebo in male subjects clinically diagnosed with ED using 
the erectile function (EF) domain of the International Index for Erectile Function (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 
Secondary Objectives 
 
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) &  erection hardness 
and  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 adverse events (AEs) and standard physico-chemical 
assessments 
Study Design: 
A Phase III, dose-ranging, multi-centre, randomised, double-blind, placebo-controlled, home use, parallel group 
clinical study to evaluate the efficacy and safety of MED2005, a topically applied GTN gel for the treatment of 
ED. The study will include a screening period, a double-blind phase and an open-label extension phase. 
Screening Period: Subjects will be screened for eligibility during a screening period between Day –43 and Day –
1. The IIEF questionnaire will be completed by the subject at the start of the screening period at the first site visit 
(Visit 1) and the EF domain of the IIEF (IIEF-EF; i.e. Questions 1–5 and 15) will be used to determine 
pre-screening eligibility of the subject. A score of ≤ 25 will be acceptable for inclusion in the screening period of 
the study. Both the male subject and his female partner will be required to attend Visit 1. Subject and partner 
training in the use of questionnaires and IMP application will be given at this visit.  
During the screening period, subjects and their partners are required to make a minimum of four attempts at 
sexual intercourse within a 4-week period (without treatment). They will be asked to complete questionnaires to 
record their experiences after each sexual intercourse attempt (using the SEP [male subjects and their female 
partners]) and at the end of the 4-week period (using the IIEF and PGI-S [male subjects only] and SEAR [male 
subjects and their female partners]) according to a prescribed schedule of questionnaires. Subjects who cannot 
comply with the minimum number of intercourse attempts or who exceed 25 on the IIEF-EF at the end of the 
screening period will be excluded from the study.  
Double-Blind Phase: Eligible subjects will participate in the double-blind phase, comprising a 12-week treatment 
period (Visits 2, 3, 4 and 5) and a 1-week follow-up visit (Visit 6). The subject and his female partner will be 
required to attend Visit 2 at the start of the double-blind phase. 
During the treatment period subjects will be randomly allocated to receive placebo or one of three doses of 
MED2005 (0.6 mg GTN, 1.2 mg GTN, 1.8 mg GTN). Subjects will be divided into sub-groups based on their 
baseline ED severity scores (from the end of the screening period): mild (IIEF-EF domain score of 17–25), 
moderate (IIEF-EF 11–16) or severe (IIEF-EF ≤ 10). The number of subjects in each of the three baseline ED 
severity groups will be monitored during the trial in order to have approximately equal numbers in each group. 

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Protocol Reference: FM57                                                Version 7.0 dated 27 July 2018 
 
At home, subjects or their partners should apply the investigational medicinal product (IMP) immediately prior to 
sexual intercourse and make at least four intercourse attempts in each of the three 4-weekly periods during 
treatment (Weeks 1–4, 5–8 and 9–12). The subjects and their partners will be asked to complete questionnaires 
using electronic patient-reported outcomes (ePRO) to record their experiences after each sexual intercourse 
attempt (using the SEP questionnaire and the onset and duration of action [erection] and erection hardness 
questions at home [male subjects and their female partners]), and at the end of each of the three 4-week periods 
during treatment (using the IIEF, PGI-S and PGI-C questionnaires [male subjects only], and the SEAR and GAQ 
questionnaires [male subjects and their female partners]; to be completed at site visits for subjects and at home 
for their partners if preferred).  
Subjects and their female partners will be monitored for AEs by being asked to complete 4-week diaries at home 
of untoward signs and symptoms as they experience them (i.e. in real time) throughout the duration of the 
double-blind phase of the study (from signing of informed consent until the follow-up assessment at Visit 6). The 
diaries will be reviewed at each study visit. 
Subjects will be asked to return to the study site at the end of each of the three 4-week (± 1 week) periods during 
treatment (i.e. at Visits 3, 4 and 5) to return used and unused IMP, to enable the clinical staff to check compliance 
and to assess subject health status, including assessment of any AEs and recording concomitant medications. 
These visits will be optional for the female partners. Subjects and their female partners will be required to attend 
a follow-up visit (Visit 6) 7 days (± 2 days) after the Week 12 visit (Visit 5). 
At the end of the double-blind phase, during Visit 6, subjects and their female partners will be invited to take part 
in the open-label extension phase at the 0.6% MED2005 (1.8 mg GTN) dose level. Participation in the extension 
phase will be at the discretion of the individual subject and his partner and if there are still available places. 
Recruitment will continue until approximately 450 subjects and their female partners have consented. The 
remaining subjects will be discharged from the study. 
Open-Label Extension Phase: The open-label extension phase will comprise 12-months treatment for eligible 
subjects, with visits every 3 months. For each 3-month period subjects will be dispensed 12 tubes per month 
(36 tubes at each visit) to allow them to use the tubes as they require. Male subjects will be asked to complete 
the SEP questionnaire to record their experiences after each sexual intercourse attempt as and when they occur. 
At each site visit male subjects will be asked to complete the IIEF questionnaire to cover the previous 1 month. 
Subjects and their female partners will be monitored for AEs by completing diaries of untoward signs and 
symptoms as they experience them (i.e. in real time) throughout the duration of the open-label extension phase. 
Once they have entered the open-term extension phase, male subjects will be asked to return to the study site 
every 3 months (at Day 180 [Visit 7], Day 270 [Visit 8], Day 360 [Visit 9] and Day 450 [Visit 10]) to enable the 
clinical staff to check AEs and concomitant medications (in the diaries), SEP questionnaire completed after each 
intercourse attempt to cover each 3-month period, IIEF to cover previous 1-month period and compliance on IMP 
usage. Vital signs and a penis examination will be undertaken at each 90 day visit. An electrocardiogram (ECG) 
will be done at 12 months (Day 450). Visits during the open-label extension phase will be optional for the female 
partners. 
Number of Subjects: 
Double-Blind Phase: It is planned to randomise and treat 250 male subjects for each of the four treatment groups, 
clinically diagnosed with ED, and their female partners (total N = 1000).  
Open-Label Extension Phase: It is planned to include a total of 450 male subjects who have completed the 
double-blind phase of the study, and their female partners. 
Diagnosis and Main Criteria for Admission: 
Double-Blind Phase: Male subjects aged 18–70 years with a confirmed clinical diagnosis of ED for more than 
3 months (according to the National Institutes of Health Consensus Statement ‘the inability to achieve or maintain 
penile erection sufficient for satisfactory sexual performance at least once’), verified by the IIEF-EF domain (a 
score of ≤ 25 points at the end of the screening period) and involved in a continuous heterosexual relationship 
with their partner for at least 6 months. 
Exclusion criteria include: any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, 
haematological, endocrinological, metabolic, neurological or psychiatric disease; any history of an unstable 
medical or psychiatric condition or using any medication that, in the opinion of the Principal Investigator (PI), is 
likely to affect the subject's ability to complete the study or precludes the subject’s participation in the study. 
Open-Label Extension Phase: Subjects who complete the double-blind phase, were compliant to study 
procedures and who consent to the open-label extension phase. 
Exclusion criteria include: 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. 

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Study Treatments and Mode of Administration: 
Double-Blind Phase: Subjects will be randomly allocated in a 1:1:1:1 ratio to receive one of the following gel 
treatments according to a parallel group design (i.e. subjects will receive one treatment only): 
 
MED2005 0.2% (w/w) GTN gel to deliver a 0.6 mg dose of GTN 
 
MED2005 0.4% (w/w) GTN gel to deliver a 1.2 mg dose of GTN 
 
MED2005 0.6% (w/w) GTN gel to deliver a 1.8 mg dose of GTN 
 
Placebo vehicle 
Randomisation will be carried out on Day 1 of the treatment period of the double-blind phase (Visit 2) according 
to an interactive voice/web response system (IVRS/IWRS), stratified by baseline ED severity. No stratification by 
site will be done. During the treatment period, the subjects or their partners will be required to topically apply a 
single dose (approximately 300 mg) to the glans of the penis and rub in for at least 15 seconds (to ensure 
thorough distribution of the gel and promote penetration of the active substance) immediately prior to sexual 
intercourse. Subjects will be asked to leave a washout period of at least 12 hours before the next attempt at 
sexual intercourse using the IMP gel. 
Open-Label Extension Phase: All subjects will receive treatment with MED2005 0.6% (w/w) GTN gel to deliver 
a 1.8 mg (0.6%) dose of GTN. The gel is to be used as described above for the double-blind phase. 
Reference Treatment and Mode of Administration: 
Placebo vehicle gel, identical in appearance to the three active MED2005 gels. The placebo gel will be 
administered as a single dose in the same way and at the same volume as MED2005. 
Duration of Treatment: 
Double-Blind Phase: Eligible subjects will participate in a 12-week treatment period (Visits 2, 3, 4 and 5) and a 
1-week follow-up visit (Visit 6). Subjects will be asked to apply the IMP immediately prior to sexual intercourse 
and to make at least four intercourse attempts in each of the three 4-weekly periods during treatment (Weeks 1–
4, 5–8 and 9–12). 
Open-Label Extension Phase: Eligible subjects will participate for a further 360 days of treatment (Visits 7, 8, 9 
and 10). Subjects will use the IMP immediately prior to sexual intercourse as they require. 
Criteria for Evaluation: 
Efficacy Assessments: 
Efficacy will be evaluated using questionnaires (IIEF, SEP, SEAR, GAQ, PGI-S, PGI-C) as well as subjective 
measures of time of onset and duration of action (erection) and erection hardness. The co-primary efficacy 
outcomes will be the IIEF-EF domain, SEP Question 2 and SEP Question 3, completed by the male subjects. 
Information on usage and application of the gels will be evaluated. 
Safety Assessments: 
Safety will be evaluated throughout the double-blind phase using standard assessments including physical 
examinations and visual examination of the penis, vital signs (blood pressure [BP], heart rate [HR], body 
temperature), standard clinical laboratory safety tests (haematology, biochemistry, urinalysis), 12-lead ECGs and 
monitoring of AEs and concomitant medications with paper diaries (potential partner AEs will be captured at site 
visits or by telephone). Safety will be evaluated throughout the open-label extension phase by monitoring of AEs 
and concomitant medications with paper diaries (potential partner AEs will be captured at site visits or by 
telephone), monitoring of vital signs, ECGs, and visual examination of the penis. 
Statistical Methods: 
In general, safety and efficacy variables will be presented by means of descriptive statistics and figures, as 
appropriate, by treatment (active at each dose level and placebo) and by time point and gender, if applicable.  
A Bonferroni correction will be used to take into account that there are three active versus placebo comparisons; 
i.e. all p-values resulting from comparing the three different MED2005 doses (0.6 mg GTN, 1.2 mg GTN, 1.8 mg 
GTN) versus placebo will be multiplied by three and statistical significance will then be declared if p < 0.05. 
Corresponding Bonferroni corrected 95% confidence intervals will be produced. 
Efficacy Analyses: 
Double-Blind Phase: Primary and secondary analyses will be performed on the Full Analysis Set (FAS; all 
randomised subjects who used medication at least once). 
The co-primary efficacy endpoints, assessed in the male subjects, are:  
 
The change from baseline of the average of the Week 4, Week 8 and Week 12 IIEF-EF domain scores 
 
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 
 
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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The primary objective will be assessed by testing hypotheses for each MED2005 group (0.6 mg GTN, 1.2 mg 
GTN or 1.8 mg GTN) separately. The basic statistical model for the primary analysis for all three co-primary 
endpoints is an analysis of covariance (ANCOVA) including terms for treatment group, site and baseline (as a 
continuous variable). Baseline ED severity (mild, moderate or severe, based on Visit 2 IIEF-EF) will be included 
in the analysis of the SEP questions, and will be included in the analysis of IIEF-EF as a sensitivity analysis. The 
estimated treatment means and differences (MED2005 versus placebo) will be reported as part of this analysis. 
The objective is for all co-primary endpoints to show superiority of MED2005 to placebo in order to conclude a 
significant result. No adjustment for multiplicity of the error probability for the individual co-primary endpoints is 
required. However, the three co-primary endpoints will still be considered in a hierarchy of their importance: 
IIEF-EF domain, SEP Question 3 and SEP Question 2. 
The following secondary efficacy analyses will be performed in a supportive way to describe the effect of 
treatment: 
 
The analysis of the three co-primary endpoints will be repeated in the three pre-specified subgroups of 
ED severity: mild, moderate and severe 
 
The change in the IIEF-EF domain, SEP Question 2 and SEP Question 3 at each 4-week visit will be 
analysed 
 
Responder analyses assessing the proportion of subjects with a specific increase in the IIEF-EF domain 
from baseline, using a different responder definition defined separately for each baseline severity group 
 
Responder analyses for SEP Questions 2 and 3 will be conducted in the same way as for the IIEF-EF 
 
Responder analyses will also be conducted using responder thresholds (that represent meaningful 
within-patient changes) in the three co-primary endpoints that are determined using anchor-based 
methods. The thresholds will be defined using a suitable set of data from this study prior to study 
unblinding. 
The following secondary efficacy analyses will be conducted in a more exploratory way: 
 
The GAQ will be analysed via logistic regression including terms for treatment group, site and baseline 
ED severity (categorical variable) 
 
The change in the other domains of the IIEF questionnaire, the other SEP questions (Questions 1, 4 
and 5), the overall SEAR questionnaire score, the scores in the two subdomains of the SEAR 
questionnaire (sexual relationship satisfaction and confidence), the PGI-S at time points 4, 8 and 
12 weeks will be analysed using ANCOVA as described for the primary endpoint analysis. The PGI-C 
will be analysed using an analysis of variance (ANOVA) 
 
Subjective measures of the time of onset and duration of action (erection) and erection hardness will be 
analysed using an ANCOVA model fitted to the average of Wilcoxon Rank Scores 
 
Usage and application question responses will be summarised by treatment group 
All efficacy assessments provided by the female partners will be analysed using the same statistical models as 
for the male subjects. 
Open-Label Extension Phase: Efficacy assessments will be summarised, including (where applicable) changes 
from baseline, where the baseline assessments are the ones prior to the double-blind phase. 
Safety Analyses 
Summary statistics will be presented for scheduled assessments and change from baseline for vital signs, ECGs 
and clinical laboratory safety tests. 
Dosing duration and frequency will be summarised. 
AEs will be listed by system organ class (SOC) and preferred term (PT) classifications assigned to the event 
using the Medical Dictionary for Regulatory Activities (MedDRA; Version 20.1 or higher). The number of AEs and 
number (and %) of subjects with AEs will be summarised by SOC and PT. In addition, AEs will be summarised 
by severity, relationship to treatment, time to onset (from the last dose of IMP prior to AE start date) and duration 
(offset).  
Listings will be presented of serious adverse events (SAEs) and AEs leading to withdrawal. 

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6. 
INTRODUCTION 
6.1 
Background 
Erectile dysfunction (ED) is a chronic condition affecting male sexual function and has a 
significant health economic impact worldwide. It has been surmised that if all men in the United 
States (US) sought care for ED, the cost of treatment in the US alone would reach $15 billion 
[1]. Although it can affect all age groups, the frequency of ED increases with age. The 
probability of ED triples from 5% in men aged 40 years to 15% in men aged 70 years [2]. A 
recent study which evaluated ED in men aged 40–79 years suggested that the prevalence of 
ED was highest in men aged 70 years or older [3]. When adjusted for age, patients with 
cardiovascular disease and diabetes have an increased risk of ED [4]. Given the increase in 
life expectancy across the western world coupled with higher frequencies of cardiovascular 
disease and diabetes, it is predicted that by 2025 the global prevalence of ED will be 
approximately 322 million, which could contribute to a significant cost burden on healthcare 
systems [5]. 
ED is a multi-factorial condition with a treatment trajectory compounded because aging men 
are often affected with several diseases, leading to polypharmacy and treatment regimens that 
could potentially worsen the ED. According to the National Institutes of Health (NIH) 
Consensus Development Conference, ED can be defined as ‘the persistent inability to achieve 
or maintain penile erection sufficient for satisfactory sexual performance’ [6]. In view of this 
definition, the NIH also recommends the use of ‘erectile dysfunction’ as the agreed term 
instead of ‘impotence’.  
The treatment of ED usually follows a circuitous route. Erectile function (EF) involves a 
complex coordination of physiological processes and as such the management of ED reflects 
this complexity. Evidence suggests that 80% of ED cases are of organic origin [6]. These 
organic causes are diverse and include, but are not limited to, vascular disorders (such as 
cardiovascular disease, hypertension), iatrogenic factors (such as hormonal agents, 
beta-blockers), penile injury/anatomic abnormalities (such as Peyronie's disease, priapism) 
and endocrine disorders (such as diabetes, hypogonadism). The most frequent organic causes 
of ED are thought to be vascular in origin and patients frequently present with decreased blood 
flow to the penis owing to cardiovascular disease [7]. Many cases of ED are characterised as 
‘vascular’ indicating a correlation with cardiovascular risk factors and events [8].  
Usually, first-line therapies for the treatment of ED are lifestyle changes (exercise and weight 
loss) and modifications to risk factors [9], followed by treatment with oral phosphodiesterase 
type 5 (PDE-5) inhibitors such as sildenafil, tadalafil or vardenafil [10]. Other treatments such 
as intracavernosal injections [11] and intraurethral suppositories have been used previously; 
however, these treatments are frequently associated with adverse events (AEs) such as local 
pain and priapism and poor compliance owing to their invasive nature [12]. Topical 
prostaglandin E1 (PGE 1) has been used for the treatment of ED [13]. In one study, the 
treatment was safe, well-tolerated and significantly increased penile blood flow in 8 patients. 
The treatment has gained popularity owing to its ease of use [14], and the topical administration 
of alprostadil (a synthetic form of PGE 1) is licensed for the treatment of ED in men aged 
≥ 18 years [15]. Owing to their less invasive routes of administration and ease of use, topical 
therapies approved for other indications have been explored as alternative candidates for the 
treatment of ED.  
Although PDE-5 inhibitors are widely used in ED and their side-effects have been well 
documented, all PDE-5 drugs are contraindicated in patients taking nitrates (such as glyceryl 

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trinitrate [GTN], a potent smooth muscle vasodilator) for cardiovascular disease. From an 
epidemiological perspective this fact has broader implications given the putative link between 
ED and cardiovascular disease in the elderly.  
The vasodilator GTN is a well-known and well documented therapeutic agent. GTN has 
established clinical use for the prophylaxis of angina. It is usually administered inter-nasally, 
orally or sublingually as short- or long-acting tablets and sprays, or transdermally via patches 
or topical ointments. Clinical data for nitric oxide (NO) donors and their impact on ED is less 
extensive compared with PDE-5 inhibitors; however, available evidence suggests that NO 
donors, for example topically applied GTN, might be a potentially useful approach to the 
management of sexual dysfunction [16]. Topical GTN is also licensed for the treatment of anal 
fissure. 
The first case of an organic nitrate improving ED was reported in 1977 in a patient taking 
sublingual GTN. Since then, several studies have shown that GTN (either as a topical ointment 
at concentrations ranging from 2 to 10%, or as a topical plaster) is effective in increasing penile 
tumescence in patients with organic, psychogenic or mixed ED with no significant differences 
between ED subtypes [17]. Whilst so far there is little empirical evidence on the effect of topical 
GTN on ED, one study has shown that topical application of a cream containing the NO donor, 
isorbide dinitrate, is efficacious [18]. In a randomised, double-blind, placebo-controlled study, 
21 out of 36 men with ED reported full erection and satisfactory intercourse after 1 week of 
treatment with an active cream containing aminophylline 3%, isosorbide dinitrate 0.25% and 
co-dergocrine mesylate 0.05% versus placebo. There were no cases of priapism or significant 
AEs, and none of the 21 subjects reported complaints from their partner.  
6.2 
Rationale for Conducting Study 
In light of the recent literature, Futura Medical Developments Ltd (FMD) are developing a gel 
formulation of GTN (MED2005) as a topical treatment for ED delivered using DermaSys®, a 
versatile and bespoke technology. Of particular interest are subjects who are currently taking 
chronic oral nitrate therapy, for whom the use of oral PDE-5s are contraindicated. 
FMD has conducted three Phase I, dose-ranging clinical studies with MED2005: a 
pharmacokinetic (PK) study (Study FM33), a pharmacodynamic (PD) study (FM35), which 
used penile blood flow changes as a surrogate marker of efficacy; a second PK study 
(Study FM58) and one Phase IIa study in male subjects clinically diagnosed with ED (Study 
FM53). In view of the results of these studies (see Section 6.3 below), FMD is further 
developing MED2005 for the intended treatment of ED in male subjects  
6.3 
Clinical Studies with MED2005 
For further details of the clinical studies carried out with MED2005, please refer to the current 
version of the FMD MED2005 Clinical Investigator’s Brochure (IB). 
6.3.1 
Pharmacokinetics 
The Phase I PK study (FM33) demonstrated a dose-response relationship with regard to 
plasma levels of GTN in 16 healthy male volunteers. The time to reach the maximum plasma 
concentration (tmax) ranged between 6.5 and 9.0 minutes, and the terminal elimination half-life 
(t1/2) was approximately 4 minutes. The second Phase 1 PK study (FM58 PK), the CSR for 
which has yet to be finalised, demonstrated a dose response relationship with regards to 
plasma levels in 30 healthy male volunteers. The tmax ranged between 10-12 minutes. The data 

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suggested that MED2005 doses in the range of 0.2%-0.6% may be optimum for further efficacy 
and safety studies. 
6.3.2 
Pharmacodynamics 
The Phase I volunteer study (FM35) has shown evidence of PD effects supportive of the 
intended indication. This single-centre, placebo-controlled, double-blind, dose-ranging, 
crossover study assessed the physiological effects of GTN gels on application to the glans 
penis in 15 healthy male volunteers. The study, which used Doppler ultrasound to measure 
penile blood flow, was not powered to produce statistically significant outcomes. However it 
provided a complex data set from which the following conclusions were drawn: 
 
MED2005 appeared to stimulate penile blood flow in a number of subjects relative to 
placebo 
 
Some vascular changes (penile artery, peak systolic velocity, end diastolic velocity) 
achieved statistical significance with certain doses at certain time points 
 
MED2005 at a dose of 0.6 mg appeared to induce a greater effect on blood flow than 
any of the other doses used 
 
Dr Paul Sidhu, a Consultant at Kings College Hospital, London and an expert in the use 
of Doppler ultrasound, commented that the blood flow changes induced by MED2005 
were consistent with the erection process and therefore that these data were 
encouraging in regard to GTN's proposed erectogenic action 
6.3.3 
Efficacy and Safety 
The efficacy and safety of MED2005 was assessed in a recent Phase IIa, multi-centre, 
randomised, double-blind, placebo-controlled, crossover study in male subjects clinically 
diagnosed with ED (Study FM53). The application of 0.6 mg MED2005 gel to the glans penis 
was associated with a statistically significant increase (i.e. improvement) in the EF domain 
score of the International Index for Erectile Function (IIEF; the primary endpoint) compared 
with a placebo gel. The efficacy of MED2005 compared with placebo was further supported by 
the analyses of the secondary efficacy outcome variables.  
The tolerability and safety profile of MED2005 appears to be predictable and consistent with 
the known pharmacological profile of GTN. In Study FM53, 15 mild related headaches were 
reported in 1023 intercourse attempts and only 2 mild related headaches were reported by the 
female partners. 
The Phase I, healthy volunteer studies FM33, FM35 and FM58 demonstrated a favourable 
safety profile of MED2005. There was a low incidence of mild transient headache, no clinically 
significant effects on blood pressure (BP) and no serious adverse events (SAEs). In the Phase 
IIa study in male subjects clinically diagnosed with ED (FM53), a locally applied dose of 
MED2005 was considered safe, well-accepted and well-tolerated by the male subjects and 
their female partners. FMD has also conducted a single-blind, placebo-controlled, 
dose-ranging study to assess the physiological effects and tolerability of a different GTN gel 
formulation (Zanafil) applied to the vaginas of a group of healthy, pre-menopausal, female 
volunteers (Study FM22). No AEs were reported following vaginal application of 0.5 mg and 
1 mg doses of GTN gel. This suggests that even if the full dose of MED2005 was transferred 
to the female partner during sexual intercourse, it would be unlikely to cause any notable 
tolerability problems.  

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For further safety information, please refer to the ‘Reference Safety Information’ of the current 
version of MED2005 IB. 
Additional studies in subjects with ED are required to further demonstrate the efficacy and 
safety of MED2005. This is the reason for the current study. 
6.4 
Risk-Benefit Evaluation 
6.4.1 
Potential Benefits 
MED2005 is being developed for the treatment of ED and as such, subjects receiving treatment 
with MED2005 might benefit from improvements in EF and quality of life for themselves and 
their partners. 
6.4.2 
Potential Risks 
Preclinical studies demonstrate that GTN does not possess teratogenic potential, has no 
adverse effects on male or female reproductive organs and is unlikely to have the potential to 
cause sensitisation or irritation at the intended site of application in men or women. 
Published clinical studies and literature reports confirm the pharmacologically predictable 
tolerability profile of GTN. The most common AEs that have been reported are headache 
(generally mild and short-lived) and hypotension (not normally symptomatic). The literature 
reports relative success following the application of GTN transdermal patches or GTN ointment 
to the shaft of the penis. 
GTN has been used in clinical practice in numerous countries for more than 100 years for the 
treatment of angina pectoris and other cardiovascular conditions. The side-effects of GTN are 
well documented and reports indicate that the most common undesirable effects include 
headache, facial flushing and nausea. In subjects treated with GTN ointments, for example for 
rectal pain or angina prophylaxis, the reported AEs are similar to those documented for other 
GTN treatments. For the treatment of rectal pain, the most commonly reported 
treatment-related AEs using Rectogesic® 4 mg/g rectal ointment were dose-dependent 
increases in headache (57% of subjects) followed by dizziness and nausea [19]. For 
prophylaxis of angina pectoris, AEs related to Percutol® 2% ointment have also been shown 
to be dose-related and almost all were the result of vasodilator activity. Headache was the 
most commonly reported AE [20]. Other commonly reported AEs with GTN 2% ointment 
include nausea and vomiting. Uncommon side-effects include cardiac disorders (tachycardia, 
bradycardia [in the presence of syncope]), vascular disorders (hypotension, circulatory 
collapse), allergic skin disorders (eczema, dermatitis, pruritus, urticaria, non-specific rashes) 
and immune system disorders (hypersensitivity reactions, anaphylaxis). 
The study is designed for careful monitoring of any potential AEs of MED2005. 
6.5 
Conduct of the Study 
This study will be performed in compliance with the protocol, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) and applicable regulatory requirements 
including European Union (EU) Good Manufacturing Practice (GMP) requirements for 
investigational medicinal products (IMPs). 

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7. 
STUDY OBJECTIVES  
7.1 
Primary Objective 
 
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 
7.2 
Secondary Objectives 
 
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  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 
8. 
STUDY DESIGN 
8.1 
Overall Study Design and Plan 
This is a Phase III, multi-centre, randomised, double-blind, placebo-controlled, home use, 
parallel group clinical study to evaluate the efficacy and safety of MED2005, a topically applied 
GTN gel for the treatment of ED. The study will include a screening period, a double-blind 
phase and an open-label extension phase. 
The study population will comprise male subjects aged between 18 and 70 years clinically 
diagnosed with ED, and their female partners. A total of 1000 subjects are planned to be 
randomised and treated in the double-blind phase of the study at a suitable number of sites 
within Eastern Europe. After completing the final follow-up visit (Visit 6) in the double-blind 
phase, subjects and their female partners will be invited to take part in the 12-month open-label 
extension phase. Participation in the extension phase will be at the discretion of the individual 
subject and his partner. Recruitment will continue until approximately 450 subjects and their 
partners have consented to participate in the open-label extension phase.  

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During the double-blind phase, treatment will involve topical self- or partner-administration of 
a gel to the glans penis prior to attempting sexual intercourse. Subjects will be randomised to 
receive one of the following gel treatments in a 1:1:1:1 ratio: 
 
MED2005 0.2% (w/w) GTN gel to deliver a 0.6 mg dose of GTN 
 
MED2005 0.4% (w/w) GTN gel to deliver a 1.2 mg dose of GTN 
 
MED2005 0.6% (w/w) GTN gel to deliver a 1.8 mg dose of GTN 
 
Placebo vehicle 
During the open-label extension phase, all subjects will receive MED2005 0.6% (w/w) GTN gel 
to deliver a 1.8 mg dose of GTN.  
Subjects will be screened for eligibility during a screening period between Day –43 and Day –
1. The IIEF questionnaire will be completed by the male subjects at the start of the screening 
period at the first site visit (Visit 1) and the EF domain of the IIEF (IIEF-EF; i.e. Questions 1–5 
and 15) will be used to determine the pre-screening eligibility of the subject. A score of ≤ 25 
will be acceptable for inclusion in the screening period of the study. Informed consent will be 
signed by male subjects and their female partners during screening (Visit 1) before they can 
be admitted into the study. There will also be subject and partner training in the use of 
questionnaires and IMP application at Visit 1.  
During the screening period, at home and after refraining from using other ED treatments for 
a period of at least 14 days, subjects and their partners are required to make a minimum of 
four attempts at sexual intercourse, at their convenience but within a 4-week period (without 
treatment). The subjects and their partners will be asked to complete questionnaires to record 
their experiences after each sexual intercourse attempt (using the SEP questionnaire at home 
[male subjects and their female partners]) and at the end of the 4-week period (using the IIEF 
and PGI-S [male subjects only], and the SEAR [male subjects and their female partners] 
questionnaires). The IIEF-EF completed at the end of the screening period will be used to 
confirm eligibility for randomisation. Subjects who cannot comply with the minimum number of 
intercourse attempts verified by completed SEPs or who exceed 25 on the IIEF-EF will be 
excluded from the study. This eligibility check will be completed prior to randomisation and 
dosing. The scores generated from the screening period will be used as an established 
baseline in the planned analyses. 
Eligible subjects will then participate in the double-blind phase, comprising a 12-week 
treatment period (Visits 2, 3, 4 and 5) and a 1-week follow-up visit (Visit 6). Male subjects will 
be required to attend all study visits. The female partner will be required to attend Visits 1, 2 
and 6; attendance at the other visits (Visits 3, 4 and 5) will be optional. 
During the treatment period, subjects will be randomly allocated to receive placebo or one of 
the three doses of MED2005 (0.6 mg GTN, 1.2 mg GTN or 1.8 mg GTN). Randomisation will 
be carried out on Day 1 of the treatment period (Visit 2) using an interactive voice/web 
response system (IVRS/IWRS). Subjects will be stratified for randomisation based on their 
baseline ED severity scores from the end of the screening period (see Section 9.5 for details). 
The number of subjects in each of the three baseline ED severity groups (i.e. mild, moderate 
and severe) will be monitored during the trial in order to have approximately equal numbers in 
each group.  
Training on the application of the IMP will be repeated/ reinforced. Medication will be dispensed 
on Day 1 of the treatment period (Visit 2): 12 units will be supplied for each 4-week period. At 

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home, subjects or their partners should apply the dispensed gel immediately prior to sexual 
intercourse and make at least four intercourse attempts in each of the three 4-weekly periods 
during treatment (Weeks 1–4, 5–8 and 9–12). Subjects will be asked to leave a washout period 
of at least 12 hours before the next attempt at sexual intercourse using the IMP. The subjects 
and their partners will be asked to complete questionnaires using electronic patient-reported 
outcomes (ePRO) to record their experiences after each sexual intercourse attempt (using the 
SEP questionnaire and the onset and duration of action [erection] and erection hardness 
questions at home [male subjects and their female partners]), and at the end of each of the 
three 4-week periods during treatment (using the IIEF, PGI-S and PGI-C questionnaires [male 
subjects only], and the SEAR and GAQ questionnaires [male subjects and their female 
partners]; to be completed at site visits for subjects and at home for their partners if preferred).  
Subjects and their female partners will be monitored for AEs by being asked to complete 
4-week diaries at home of untoward signs and symptoms as they experience them (i.e. in real 
time) throughout the duration of their participation in the double-blind phase of the study (from 
signing of informed consent until the follow-up assessment at Visit 6). The diaries will be 
reviewed at each study visit. 
Subjects will be asked to return to the study site at the end of each of the three 4-week 
(± 1 week) periods during treatment (i.e. at Visits 3, 4 and 5) to return used and unused IMP, 
to enable the clinical staff to check compliance and to assess subject health status, including 
assessment of any AEs and recording concomitant medications. At these visits, dispensed 
IMP tubes will be visually inspected to check if the tube has been pierced to help assess subject 
compliance and allow re-training on expressing a dose if deemed necessary. These visits will 
be optional for the female partners. 
Subjects and their female partners will be required to attend a follow-up visit (Visit 6), 7 days 
(± 2 days) after the Week 12 visit (Visit 5) for safety assessment. At the end of the double-blind 
phase, during Visit 6, subjects and their partners will be invited to take part in the open-label 
extension phase. Participation in the extension phase will be at the discretion of the individual 
subject and his partner. Recruitment will continue until approximately 450 subjects and their 
female partners have consented. The remaining subjects will be discharged from the study. 
The open-label extension phase will comprise 12-months treatment with visits every 3 months. 
During the extension phase, all subjects will receive MED2005 0.6% (w/w) GTN gel to deliver 
a 1.8 mg dose of GTN. Treatment will involve topical self- or partner-administration of the gel 
to the glans penis immediately prior to attempting sexual intercourse. Subjects will be asked 
to leave a washout period of at least 12 hours before the next attempt at sexual intercourse 
using the IMP gel. Training on the application of the IMP will be provided and 
repeated/reinforced as necessary throughout the extension phase. 
For each 3-month period subjects will be dispensed 12 tubes per month (36 tubes at each visit) 
to allow them to use the tubes as they require. Male subjects will be asked to complete the 
SEP questionnaire to record their experiences after each sexual intercourse attempt as and 
when they occur. At each site visit male subjects will be asked to complete the IIEF 
questionnaire to cover the previous 1 month. Subjects and their female partners will also be 
monitored for AEs by completing diaries of untoward signs and symptoms as they experience 
them (i.e. in real time) throughout the duration of the open-label extension phase. 
Once they have entered the open-label extension phase, subjects will be asked to return to 
the study site every 3 months (at Day 180 [Visit 7], Day 270 [Visit 8], Day 360 [Visit 9] and Day 
450 [Visit 10]) to enable the clinical staff to check AEs and concomitant medications (in the 

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diaries), SEP questionnaire completed after each intercourse attempt to cover each 3-month 
period, IIEF to cover previous 1-month period and compliance on IMP usage. Vital signs and 
a penis examination will be undertaken at each visit. An electrocardiogram (ECG) will be done 
at 12 months (Day 450). Visits during the open-label extension period will be optional for 
female partners. 
Subject participation in the double-blind phase will comprise 12 weeks of treatment and a 
1-week follow-up visit. Subjects who continue in the open-label extension phase will 
participate for a further 360 days of treatment. The end of the study will be the last visit of the 
last subject.  
Efficacy will be evaluated using questionnaires (IIEF, SEP, SEAR, GAQ, PGI-S, PGI-C) as 
well as subjective measures of time of onset and duration of action (erection) and erection 
hardness. Information on usage and application of the gels will be evaluated.  
Safety will be evaluated throughout the double-blind phase using standard assessments 
including physical examinations and visual examination of the penis, vital signs (BP, heart rate 
[HR], body temperature), standard clinical laboratory testing (haematology, biochemistry, 
urinalysis), 12-lead ECGs, alcohol and drugs of abuse testing, serology testing, pregnancy 
testing (females of childbearing potential only) and recording of AEs and concomitant 
medications with paper diaries (potential partner AEs will be captured at site visits or by 
telephone). Safety will be evaluated throughout the open-label extension phase by monitoring 
of AEs and concomitant medications with paper diaries (potential partner AEs will be captured 
at site visits or via telephone call), monitoring of vital signs, ECGs, and visual examination of 
the penis.  
All assessments are detailed in the schedule of events below (Table 1). The timetable for 
completion of the questionnaires for evaluating efficacy is detailed in the schedule of 
questionnaires below (Table 2). 
 
 

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Table 1 
Schedule of Events 
Assessments/ 
procedures 
Screening 
period 
Double-blind phase 
Open-label extension phase 
Screening 
Treatment period 
Follow-
upa,b 
 
 
Day –43 
to  
Day –1 
Day 1 
Week 1 
End of 
Week 4 
(± 1 week) 
End of 
Week 8 
(± 1 week) 
End of 
Week 12 
(± 1 week) 
Visit 5 + 
7 days 
( 2 days) 
Visit 5 + 
7 days 
( 2 days) 
Day 180 
(± 7 days) 
Day 270 
(± 7 days) 
Day 360 
(± 7 days) 
Day 450 
(± 7 days) 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Male subject 
attendance 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Female partner 
attendance 
X 
X 
 
 
 
X 
 
 
 
 
 
Informed consent 
(M+F) 
X 
 
 
 
 
 
X 
 
 
 
 
Eligibility check 
Xc 
X 
 
 
 
 
X 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
Physical 
examinationd 
X 
X 
 
 
X 
X 
 
X 
X 
X 
X 
Height, body weight, 
BMI 
X 
 
 
 
 
 
 
 
 
 
 
Alcohol breath test 
X 
 
 
 
 
 
 
 
 
 
 
Haematology 
X 
 
X 
X 
X 
 
 
 
 
 
 
Biochemistry 
X 
 
X 
X 
X 
 
 
 
 
 
 
Serologies 
X 
 
 
 
 
 
 
 
 
 
 
Endocrinologye 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
X 
 
X 
X 
X 
 
 
 
 
 
 
Urine drugs of abuse 
X 
 
 
 
 
 
 
 
 
 
 
Training in the use 
of subject 
questionnaire and 
IMP applicationf 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
 
X 
 

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Protocol Reference: FM57                                                                                                                                  Version 7.0 dated 27 July 2018 
 
Table 1 
Schedule of Events 
Assessments/ 
procedures 
Screening 
period 
Double-blind phase 
Open-label extension phase 
Screening 
Treatment period 
Follow-
upa,b 
 
 
Day –43 
to  
Day –1 
Day 1 
Week 1 
End of 
Week 4 
(± 1 week) 
End of 
Week 8 
(± 1 week) 
End of 
Week 12 
(± 1 week) 
Visit 5 + 
7 days 
( 2 days) 
Visit 5 + 
7 days 
( 2 days) 
Day 180 
(± 7 days) 
Day 270 
(± 7 days) 
Day 360 
(± 7 days) 
Day 450 
(± 7 days) 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Urine pregnancy test 
(females of 
childbearing 
potential only)g 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
Randomisation 
 
X 
 
 
 
 
 
 
 
 
 
Dispensing of 
medication suppliesh 
 
X 
X 
X 
 
 
X 
X 
X 
X 
 
Study drug 
administration 
 
 
 
 
Return and visual 
inspection of 
medication supplies 
 
 
X 
X 
X 
 
 
X 
X 
X 
X 
IIEF questionnairei 
Xj 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
SEP questionnairei, k 
 
 
 
SEAR questionnairei 
X 
X 
X 
X 
X 
 
 
 
 
 
 
GAQi 
 
 
X 
X 
X 
 
 
 
 
 
 
PGI-Si 
X 
X 
X 
X 
X 
 
 
 
 
 
 
PGI-Ci 
 
 
X 
X 
X 
 
 
 
 
 
 
Onset/duration of 
action (erection) and 
erection hardness 
questions 
 
 
 
 
 
 
 
 
 
Usage and 
application 
 
 
 
 
X 
 
 
 
 
 
 

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Protocol Reference: FM57                                                                                                                                  Version 7.0 dated 27 July 2018 
 
Table 1 
Schedule of Events 
Assessments/ 
procedures 
Screening 
period 
Double-blind phase 
Open-label extension phase 
Screening 
Treatment period 
Follow-
upa,b 
 
 
Day –43 
to  
Day –1 
Day 1 
Week 1 
End of 
Week 4 
(± 1 week) 
End of 
Week 8 
(± 1 week) 
End of 
Week 12 
(± 1 week) 
Visit 5 + 
7 days 
( 2 days) 
Visit 5 + 
7 days 
( 2 days) 
Day 180 
(± 7 days) 
Day 270 
(± 7 days) 
Day 360 
(± 7 days) 
Day 450 
(± 7 days) 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
questionsl 
Vital signs (BP 
[supine and 
standing], HR, body 
temperature)m 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
ECGn 
X 
 
 
 
X 
 
 
 
 
 
X 
Concomitant 
medications 
recordingo 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
AE reviewo 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
Invitation to 
open-label extension 
 
 
 
 
 
X 
 
 
 
 
 
 
a Subjects and their female partners will return to the study site to have a follow-up 7 days (± 2 days) after their end of treatment visit in the double-blind phase. 
b At the end of the double-blind phase, and after completing their Visit 6 follow-up visit assessments, subjects and their female partners will be invited to take part in the open-label extension 
phase. Participation in the extension phase will be at the discretion of the individual subject and his partner and subject to availability of places. Visit 6 will be the end of study visit for subjects 
who do not participate in the open-label extension phase 
c Eligibility will include the IIEF questionnaire and ED history. 
d A full physical examination (including a penis examination) will be carried out at screening (Visit 1) and a brief examination, focusing on any changes since screening, will be carried out on 
Day 1 (Visit 2) and all other visits indicated in the table.  
e Morning testosterone samples will be taken for male subjects at screening (Visit 1). If the reading is below the laboratory normal range the test should be repeated using an early morning specimen. 
Repeated low levels indicate the possibility of hypogonadism and the subject should be referred for full investigation and not recruited. 
f Training in IMP application and the completion of questionnaires will be carried out at screening (Visit 1). Training in IMP application will be repeated/reinforced on Day 1 of the treatment 
period (Visit 2), and if deemed necessary also at Visits 3, 4, 6, 7, 8 and 9 (i.e. if the investigator thinks the subject/partner needs re-training on expressing a dose after visually inspecting previously 
used IMP tubes to check if the tube has been pierced).  

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Protocol Reference: FM57                                                                                                                                  Version 7.0 dated 27 July 2018 
 
g A urine pregnancy test will be completed by female subjects of childbearing potential on Day 1 of the treatment period (Visit 2; at the study site) and at the follow-up visit (Visit 6; either at the 
study site or at the subject’s home if preferred). For subjects participating in the open-label extension phase, a urine pregnancy test will also be completed by female subjects of childbearing 
potential at Visits 7, 8 9 and 10 (either at the study site or at the subject’s home if preferred). The pregnancy test kit will be provided. 
h Medication will be dispensed on Day 1 of the treatment period (Visit 2) and at Visits 3, 4, 6, 7, 8 and 9.  
i Double-blind phase: Subjects and their partners will be asked to complete questionnaires using ePRO to record their experiences after each sexual intercourse attempt, at the end of the screening 
period and at the end of each of the three 4-week periods during treatment. Subjects and their female partners should complete the SEP questionnaire and the onset and duration of action (erection) 
and erection hardness questions at home after each sexual intercourse attempt during the study. The IIEF (male subjects only) and SEAR (male subjects and their female partners) questionnaires 
will be completed at the end of the screening period (i.e. at the end of the 4-week no-treatment period) and at the end of each of the three 4-week periods during treatment. The PGI-S (male subjects 
only) will be completed at the end of Visit 1 and Visit 2 and at the end of each of the three 4-week periods during treatment. The GAQ (male subjects and their female partners) and PGI-C (male 
subjects only) will be completed at the end of each of the three 4-week periods during treatment. The IIEF, SEAR, GAQ, PGI-S and PGI-C will be completed at site visits for subjects; their female 
partners can complete the SEAR and GAQ at home if preferred.  
  Open-label extension phase: Male subjects will be asked to complete questionnaires using ePRO to record their experiences after each sexual intercourse attempt and at the end of each of the 
3-month periods during treatment. Subjects should complete the SEP questionnaire at home after each sexual intercourse attempt during the study. The IIEF questionnaire to cover the previous 
1 month will be completed at each site visit during the study. 
j Pre-screening IIEF (i.e. IIEF-EF Questions 1–5 and 15). 
k During the screening period (between site Visit 1 and Visit 2), subjects and their female partner will make at least four attempts at sexual intercourse without treatment. Subjects with less than 
four attempts at sexual intercourse or high IIEF scores (> 25) will be excluded prior to randomisation and entry into the treatment period. Subjects and their partners should complete the SEP 
questionnaire after each sexual intercourse attempt between Visit 1 and Visit 2. 
l  Questions on the usage and application of the gels will be completed by the male partner at the end of the treatment period (Visit 5). 
m For supine vital sign measurements, the subjects will be required to rest in a supine position for at least 10 minutes prior to their measurements. Standing vital signs measurements will then be 
taken after 1 minute of standing. 
n 12-lead ECG done in triplicate approximately 1 minute apart (subjects will be required to rest in a supine position for at least 10 minutes prior to their ECG measurements).  
o AEs will be monitored throughout the duration of study using paper diaries (4-week diaries during the double-blind phase, 3-month diaries during the open-label extension phase) completed by 
the subjects and their female partners at home as they experience any untoward signs and symptoms (i.e. in real time). Concomitant medications will also be monitored using the diaries. The diaries 
will be reviewed at study visits and AEs and concomitant medications will be recorded on the appropriate pages of the eCRF. For female partners the AE review can be conducted by telephone. 
Abbreviations: AE=adverse events, BMI=body mass index, BP=blood pressure, ECG=electrocardiogram, eCRF=electronic case report form; ED=erectile dysfunction, ePRO=electronic 
patient-reported outcomes, F=female, GAQ=Global Assessment Questionnaire, HR=heart rate, IIEF=International Index for Erectile Function questionnaire, IMP=investigational medicinal 
product, M=male, PGI-C=Patient Global Impression of Change, PGI-S=Patient Global Impression of Severity, SEAR=Self-Esteem And Relationship questionnaire, SEP=Sexual Encounter Profile 
questionnaire. 
 

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Table 2 
Schedule of Questionnaires 
Questionnaire  
Participant 
Schedule  
IIEF 
Male only 
 
At the start of the screening period (Visit 1) to 
determine pre-screening eligibility of the subject 
(pre-screening IIEF i.e. Questions 1–5 and 15 only) 
 
At Day 1 Week 1 (Visit 2) without treatment 
 
At the end of each of the three 4-week periods during 
treatment in the double-blind phase (Visits 3, 4 and 5) 
 
At each of the 3-month visits to cover the previous 
1 month in the open-label extension phase (Visits 7, 8, 9 
and 10) 
SEP 
Male and Female 
 
After each sexual intercourse attempt during the 4-week 
screening period (without treatment): minimum of 
4 sexual course attempts (between Visit 1 and 2)  
 
After each sexual intercourse attempt during each of the 
three 4-weekly periods during treatment (between 
Visits 2 to 5) in the double-blind phase 
 
Male only 
 
After each sexual intercourse attempt during the 
open-label extension phase 
SEAR 
Male and Female 
 
At the end of the 4-week screening period (without 
treatment; end of Visit 1)  
 
At the end of each of the three 4-week periods during 
treatment in the double-blind phase (Visits 3, 4 and 5) 
GAQ 
Male and Female 
 
At the end of each of the three 4-week periods during 
treatment in the double-blind phase (Visits 3, 4 and 5) 
PGI-S 
Male only 
 
At the end of Visit 1 and Visit 2  
 
At the end of each of the three 4-week periods during 
treatment in the double-blind phase (Visit 3, 4 and 5) 
PGI-C 
Male only 
 
At the end of each of the three 4-week periods during 
treatment in the double-blind phase (Visit 3, 4 and 5) 
Onset and duration of 
action (erection) and 
erection hardness 
Male and Female 
 
After each sexual intercourse attempt in each of the 
three 4-weekly periods during treatment in the double-
blind phase (Visits 2 to 5) 
Usage and 
application 
Male only 
 
At Visit 5 
Abbreviations: GAQ=Global Assessment Questionnaire, IIEF=International Index for Erectile Function questionnaire, 
PGI-C=Patient Global Impression of Change, PGI-S=Patient Global Impression of Severity, SEAR=Self-Esteem And 
Relationship questionnaire, SEP=Sexual Encounter Profile questionnaire. 
8.2 
Rationale for Study Design 
8.2.1 
Discussion of Study Design 
This study will evaluate the efficacy and safety of three doses of topically applied GTN gel 
compared with a placebo vehicle gel in male subjects clinically diagnosed with ED and their 
female partners.  
The randomised, double-blind, placebo-controlled features of the study design are intended to 
reduce the effect of selection bias on the results. The parallel group design means that multiple 
treatment arms are more practical and concerns about possible carryover effects are 
eliminated (compared with a crossover design). However, the main issue with using parallel 

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groups is the effect of inter-subject variability. The random allocation of a matching placebo is 
intended to define the placebo response and therefore clarify the effects of GTN. 
In addition, there will be a 12-month open-label extension phase starting at the end of the 
double-blind phase for approximately 450 patients. The safety and efficacy of the long-term 
use of 0.6% MED2005 (1.8 mg GTN) in subjects with ED and their female partners will be 
evaluated in the open-label extension phase. 
8.2.2 
Choice of Subjects 
The study will be conducted in adult male subjects clinically diagnosed with ED and verified by 
the IIEF-EF domain (a score of ≤ 25 points at the end of the screening period), and their female 
partners. Adult males with ED are the target population for the future intended use of 
MED2005. The selection criteria are defined in such a way that subjects eligible for 
participation in the study will be known to be free from any significant illness which could 
potentially confound the study results. 
8.2.3 
Rationale for Study Drug Dose and Schedule 
The justification for choice of doses to be tested in this study was based on PK and clinical 
data generated in earlier developmental studies with MED2005, and the clinical use of a 2.5 mg 
gel of GTN in a related FMD product. 
FMD has previously tested the following doses of MED2005: 
FMD study 
Dose 
Phase 
Number of 
Volunteers/Patients 
FM33 
MED2003 0.075 mg, 0.1 mg, 0.25 mg, 0.5 mg 
MED2004 0.75 mg MED2005 1.2 mg 
I 
16 healthy volunteers 
FM35 
MED2003 0.01 mg, 0.075 mg, 0.25 mg 
MED2005 0.6 mg 
I 
15 healthy volunteers 
FM53 
MED2005 0.6 mg 
IIa 
232 patients 
FM58 
MED2005 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg 
I 
30 healthy volunteers 
 
In the FM58 PK study, MED2005 0.6 mg, 1.2 mg, and 1.8 mg demonstrated similar or lower 
PK values than the sublingual tablet comparator (Nitrostat 1.8mg GTN); however, in some of 
the PK parameters the MED2005 2.4 mg was slightly higher compared to Nitrostat. There were 
no safety concerns for any of the studied doses of MED2005. 
FMD currently market a condom based product with an ancillary medicinal substance. The 
class III medical device incorporates a topical gel which contains 2.5 mg GTN in a non-aqueous 
base and is used to help maintain an erection. Users are exposed to the topical application of 
2.5 mg of GTN under the occlusion of the device. The extended clinical use of a 2.5 mg GTN 
gel in a class III has a validated satisfactory safety record. 
Therefore MED2005 0.6 mg, 1.2 mg, and 1.8 mg were selected for the double-blind phase of 
this study. For the open-label extension phase, all subjects will be provided with MED2005 
1.8 mg as this dose is expected to have the greatest efficacy and provide the most significant 
information on safety and efficacy. 

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During the double-blind phase subjects are asked to make at least four intercourse attempts 
using the IMP in each of the three 4-weekly period during treatment in order to get a reasonable 
assessment of the efficacy and safety of MED2005 versus placebo.  
The open-label extension phase is designed to assess long-term safety of MED2005 as it 
might be used once it is on the market. Therefore, subjects will be asked to use the IMP as 
and when they wish to and medication use will be assessed as part of the open-label analyses. 
8.2.4 
Choice of Route and Rate of Administration 
In the double-blind phase of this study, the subject or their female partner will topically apply 
one of the three MED2005 gels (0.6 mg GTN, 1.2 mg GTN or 1.8 mg GTN) or the placebo 
vehicle gel to the glans penis. In the open-label extension phase, all subjects will receive 
treatment with the 0.6% MED2005 gel to deliver a dose of 1.8 mg GTN. 
The IMP will be self- or partner-applied at home. This is the intended method of administration 
after licensing. Subjects or their partners will be required to apply a single dose (approximately 
300 mg) of gel to the glans of the penis and rub for at least 15 seconds (to ensure thorough 
distribution of the gel and promote penetration of the active substance) immediately prior to 
sexual intercourse. Subjects will be asked to leave a washout period of at least 12 hours before 
the next attempt at sexual intercourse using the IMP. 
8.2.5 
Monitoring and Communication of AEs 
AEs will be monitored throughout the duration of the study from signing of the Informed 
Consent Form (ICF) at screening (Visit 1) until the final study visit. AEs of any untoward signs 
and symptoms for both the subject and his female partner will be documented in paper diaries 
to be completed at home by the subjects and their partners as they experience them (i.e. in 
real time) during each 4-week period in the double-blind phase and each 3-month period in the 
open-label extension phase and reviewed regularly by the Principal Investigator (PI) or his/her 
delegate (potential partner AEs will be captured at site visits or by telephone). If any information 
relating to the study product becomes available after the submission of a final protocol to the 
Competent Authority which may impact on the conduct of the study, including but not limited 
to the risk and benefit evaluations underpinning approvals and subject consent, FMD shall 
notify the study site in writing as soon as practically possible and the parties will agree, in 
writing, what steps need to be taken, if any. 
8.2.6 
Study Principal Investigator, Site Facilities and Personnel 
This multi-centre study will be conducted at approximately 50 investigational sites in countries 
including Poland, Hungary, Czech republic, Slovakia, Georgia, Russia, Ukraine, Bulgaria and 
Latvia. At all sites, the study will be conducted by an experienced PI and well-trained medical, 
clinical and technical staff with experience in the conduct of clinical studies. The study is 
designed to closely monitor, treat and communicate potential expected adverse reactions 
(based on the known mode of action of the IMP) as well as potential unexpected AEs. 
8.3 
Stopping Criteria  
The study will be discontinued if any unacceptable safety findings are identified. This decision 
will be made jointly by the Chief Investigator (CI) (or deputy) and the Sponsor. A written 
document signed by the CI (or deputy) and Sponsor will be produced ratifying the decision. 
Please see Section 9.6 for possible reasons for discontinuation of an individual subject 

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The PI and the Sponsor will have joint judgment of an unacceptable tolerability profile (stopping 
criteria) based on the frequency and intensity of observed AEs (including SAEs and 
treatment-related AEs).  
Any subject suffering from a clinically relevant AE will be monitored closely and provided with 
the appropriate medical care and follow-up. 
9. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
9.1 
Number and Source of Subjects to be Studied 
It is planned to randomise and treat 1000 male subjects clinically diagnosed with ED, along 
with their female partners, in the double-blind phase of the study. Additional subjects may be 
randomised if there are a substantial number of dropouts to ensure that sufficient data are 
available for analysis; this would be detailed in a protocol amendment. Subjects will be 
identified and recruited through volunteer databases, site/clinician recruitment and/or 
advertisements as necessary.  
For the open-label extension phase, it is planned to include a total of 450 male subjects and 
their female partners. 
9.2 
Inclusion Criteria 
All subjects must meet all of the following inclusion criteria to be eligible for the study (following 
screening [Visit 1], an eligibility check will be carried out on Day 1 of the treatment period 
[Visit 2]): 
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 

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 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 

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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.  
 
9.3 
Exclusion Criteria 
Subjects are prohibited from participating in the study if they meet any of the following 
exclusion criteria (following screening [Visit 1], an eligibility check will be carried out on Day 1 
of the treatment period [Visit 2]): 
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 

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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 

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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  
9.4 
Subject Restrictions 
Subjects and their female partners will have to comply with the following restrictions:  
 
Blood donation will not be allowed at any time during the study and up to 3 months 
(90 days) after completion of the study 
 
Male subjects should not donate sperm and their female partners should not donate 
egg(s) from the time of the first administration of IMP until 3 months after the last 
administration of IMP 
 
Condoms, femidoms, diaphragms, caps or hormone rings are not permitted as a form of 
contraception in this study 
9.5 
Subject Inclusion and Randomisation 
Subjects who sign the ICF for the study at Visit 1 and undergo screening procedures will be 
identified during screening by a unique screening number. Subjects who fulfil the eligibility 
criteria will be assigned consecutive subject numbers and randomised before study medication 
is dispensed on Day 1 of the treatment period (Visit 2).  
Subjects will be randomised to receive one of the following gel treatments in a 1:1:1:1 ratio 
according to a parallel group design (i.e. subjects will receive one treatment only): 
 
MED2005 0.2% (w/w) GTN gel to deliver a 0.6 mg dose of GTN 
 
MED2005 0.4% (w/w) GTN gel to deliver a 1.2 mg dose of GTN 
 
MED2005 0.6% (w/w) GTN gel to deliver a 1.8 mg dose of GTN 
 
Placebo vehicle 
Subjects will be stratified for randomisation based on their baseline ED severity scores from 
the end of the screening period: 
 
Mild (IIEF-EF domain score of 17–25) 
 
Moderate (IIEF-EF domain of 11–16) 
 
Severe (IIEF-EF domain ≤ 10)  

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It is intended to randomise an approximately equal number of subjects for each baseline 
severity group. No stratification by site will be done as, with four treatment groups and three 
baseline ED severity strata, it is not deemed feasible without risking overall balance for 
treatments.  
If a subject discontinues from the study, the subject number will not be re-used and the subject 
will not be allowed to re-enter the study. 
Randomisation will be carried out using an IVRS/IWRS.  
For the open-label extension phase, eligible subjects who sign the ICF for the extension phase 
at Visit 6 will continue in the study. All subjects will receive MED2005 0.6% (w/w) GTN gel to 
deliver a 1.8 mg dose of GTN. 
9.6 
Withdrawal of Subjects 
Each subject (and their female partners) will be informed of their right to withdraw from the 
study at any time and for any reason. The reasons for any subject withdrawal will be recorded 
on the electronic Case Report Form (eCRF).  
9.6.1 
Criteria for Withdrawal from Study Drug 
Subjects (and their female partners) may be withdrawn from the study drug at any time. All 
subjects who withdraw from the study drug during the double-blind phase will be asked to 
continue completing the IIEF and SEP questionnaires in order to address the primary efficacy 
objective of difference between treatment policies. 
A PI will withdraw a subject from study drug at any time for any of the following reasons:  
 
If a subject experiences a serious or intolerable AE, that prevents them from continuing.  
 
If a subject incurs a significant protocol violation which impacts on their safety (this will 
be discussed on a case-by-case basis with the Sponsor).  
 
At the request of the Sponsor.  
 
If it is considered that the subject’s health is composed by remaining in the study or the 
subject is not sufficiently cooperative.  
9.6.2 
Criteria for Withdrawal from the Study 
Subjects (and their female partners) are free to withdraw from the study at any time, without 
prejudice (withdrawal of consent). 
Subjects may be withdrawn from the study at any time; however, once treatment has 
commenced, every attempt should be made to continue with the safety and IIEF and SEP 
questionnaires up to the end of the double-blind phase to ensure the safety of the subject and 
in order to address the primary efficacy objective of difference between treatment policies. 
Reasons for withdrawing a subject from the study can include: 
 
Voluntary discontinuation by the subject and/or his female partner, who are free to 
discontinue participation in the study at any time 
 
Severe non-compliance to the protocol as judged by the PI and/or Sponsor 
 
Any other reason as judged by the PI 

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9.6.3 
Procedures for Subject Withdrawal 
Subjects who withdraw from the study (and their female partners) should always be asked 
about their reason(s) for withdrawal and the presence of any AEs. Study-related AEs will be 
monitored closely and provided with the appropriate medical care and follow-up.  
10. 
STUDY AND CONCOMITANT TREATMENTS 
10.1 
Investigational Medicinal Product 
The IMP under study is MED2005, a gel formulation of GTN currently under development by 
FMD as a topical treatment for ED. The matching placebo used will be the vehicle gel 
containing no active ingredients.  
During the double-blind phase, MED2005 (at three strengths: 0.2% GTN gel, 0.4% GTN gel 
and 0.6% GTN gel) or placebo (vehicle gel) will be provided in single unit dose aluminium 
tubes with 800 mg of gel in every tube packed in cartoon boxes of 4 tubes per box. For each 
subject, 12 units will be supplied for each of the three 4-week periods during treatment (Weeks 
1–4, 5–8 and 9–12).  
During the open-label extension phase, MED2005 0.6% GTN gel will be provided in single unit 
dose aluminium tubes with 800 mg of gel in every tube packed in cartoon boxes of 4 tubes per 
box. For each 3-month period of the extension phase, 12 units per month (36 tubes at each 
visit [Visits 6, 7, 8 and 9]) will be supplied to each subject to allow them to use the tubes as 
they require.  
Each 800 mg filled tube will contain sufficient gel to apply a single dose (approximately 300 mg) 
of MED2005 (0.2%, 0.4% or 0.6%) or placebo at each application. Subjects and their female 
partners will be trained on the application of the gel to the glans of the penis and cautioned not 
to use more than one tube of gel per sexual intercourse event. Subjects will be asked to leave 
a washout period of at least 12 hours before the next attempt at sexual intercourse using the 
IMP. The placebo gel will be identical in appearance to the three active MED2005 gels and will 
be administered in the same way and at the same volume as MED2005.  
The IMP will be clearly labelled with text that is in full regulatory compliance with each 
participating country and is translated into the required language(s) for each of those countries.  
10.2 
Methods of Assigning Subjects to Treatment Groups 
See Section 9.5 above for details of randomisation. 
10.3 
Drug Accountability 
The PI, trained delegate or pharmacy staff (as applicable) is responsible for the correct storage 
of the study medication according to the manufacturer’s recommendations. The medication 
made available for this clinical study must be used in accordance with the protocol and must 
only be handled by the pharmacist or other authorised personnel. The pharmacy staff must 
maintain complete and accurate records, showing the receipt and disposition of all supplies of 
the study medication. These records must include a master record which lists the date of 
receipt of all study medication and the quantities received, and a dispensing record which 
includes all quantities dispensed, the subject numbers to whom the medication was dispensed, 
the date of each dispensing and the identification of the dispenser. IMP will not be destroyed 
without prior written confirmation from the Sponsor. The Clinical Research Organisation (CRO) 
will be responsible for coordinating the destruction of any unused medication at the sites. 

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Written proof of destruction must be kept in the Sponsor Oversight File and/or the Trial Master 
File (TMF) and Investigator Site File. 
At site visits at the end of each of the three 4-week periods during treatment in the double-blind 
phase (i.e. at Visits 3, 4 and 5) and at the end of each of the 3-month periods during the 
open-label extension phase (i.e. at Visits 7, 8, 9 and 10), subjects will be asked to return used 
and unused tubes of IMP to enable the clinical staff to check treatment compliance. Clinical 
staff will examine the IMP tubes visually to check if the tube has been pierced to help assess 
subject compliance and allow re-training on expressing a dose if deemed necessary. 
10.4 
Blinding 
10.4.1 
Methods for Ensuring Blinding 
During the double-blind phase of the study both the subjects and the investigators will be 
unaware (blinded) which of the four treatments (0.2% GTN gel, 0.4% GTN gel, 0.6% GTN gel 
or placebo gel) each subject will be administered. All four treatments will be identical in 
appearance; i.e. they will be supplied in identical 800 mg filled aluminium tubes each containing 
sufficient gel to apply a single dose of approximately 300 mg of identical clear, translucent gels 
with no smell. 
Randomisation will be carried out using an IVRS/IWRS.  
Subjects should remain blinded to the double-blind treatment during the open-label extension 
phase.  
Blinding is not applicable for the open-label treatment. 
10.4.2 
Methods for Unblinding the Study 
In an emergency, details of the assigned treatment allocation can be obtained from the 
IVRS/IWRS. This should not be done except in medical emergencies when the appropriate 
management of the subject necessitates knowledge of the treatment randomisation. The PI or 
delegate must document and report to FMD any break of the treatment allocations. FMD 
retains the right to obtain knowledge of the treatment allocations for SAEs suspected to be 
causally-related to MED2005 and that potentially require expedited reporting to the Regulatory 
Authorities and/or Ethics Committees (ECs). Treatment allocations will not be exposed for the 
planned analyses of the double-blind phase until all decisions on the evaluability of the data 
from each individual subject and his partner have been made and documented.  
10.5 
Prior and Concomitant Medications 
Subjects stabilised for a minimum of 3 months on long-term nitrate therapies such as other 
GTN products, isosorbide dinitrate and amyl or butyl nitrate for the treatment/prevention of 
angina can, at the discretion of the PI, continue their medication and enter the study. 
Prescription or non-prescription medication is allowed at the discretion of the PI as long as it 
does not have a negative impact on the safety of the subject or the integrity of the study data.  
Use of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid are permitted 
for the treatment of AEs. 
Details of previous and concomitant medications will be recorded throughout the study on the 
appropriate pages of the eCRF. 

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10.5.1 
Prohibited Medications 
Subjects are prohibited from taking the following medications: 
 
Androgens (e.g. testosterone), trazodone or anti-androgens 
 
Any therapy for ED, including within 14 days of screening 
 
Subjects taking an alpha blocker  
 
Phosphodiesterase inhibitors; e.g. sildenafil, tadalafil and vardenafil 
 
Acetyl cysteine  
 
Heparin 
 
Dihydroergotamine 
During the course of the study, subjects should not take any medication which, in the opinion 
of the PI, could interfere with the treatment procedure, recovery or assessments of safety and 
effectiveness. 
10.6 
Treatment Compliance 
During the double-blind phase subjects will be asked to return to the study site at the end of 
each of the three 4-week (± 1 week) periods during treatment (i.e. at Visits 3, 4 and 5) to return 
used and unused tubes of IMP, to enable the clinical staff to check compliance and to assess 
subject health status. At these visits, IMP tubes will be examined visually to check if the tube 
has been pierced to help assess subject compliance and allow re-training on expressing a 
dose if deemed necessary. 
During the open-label extension phase, subjects will be asked to return to the study site at the 
end of each of the 3-month (± 1 week) periods during treatment (i.e. at Visits 7, 8, 9 and 10) to 
return used and unused IMP, to enable the clinical staff to check compliance and to assess 
subject health status. At these visits, IMP tubes will be examined visually to check if the tube 
has been pierced to help assess subject compliance and allow re-training on expressing a 
dose if deemed necessary. 
11. 
STUDY ASSESSMENTS AND SCHEDULES 
11.1 
Schedule of Assessments 
All study assessments are detailed in the schedule of events (Table 1) and the schedule of 
questionnaires (Table 2) and described in detail below. 
11.1.1 
Pre-screening Assessments 
At their first site visit (Visit 1), all subjects will be required to complete the IIEF. The IIEF-EF 
will be used to determine the pre-screening eligibility of the subject. A score of ≤ 25 will be 
acceptable for inclusion in the main screening period of the study. 

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11.1.2 
Screening Assessments (Visit 1) 
Visit 1 must be attended by the male subject and his female partner. Following written informed 
consent, the following assessments should be carried out during the screening period between 
Day –43 and Day –1: 
 
Eligibility check 
 
Medical history (including history of ED and surgical history) 
 
Full physical examination (including height, weight and body mass index [BMI]) 
 
Alcohol breath test  
 
Urine drugs of abuse screen 
 
Vital signs (BP, HR and body temperature) 
 
Laboratory safety assessments (haematology, biochemistry and urinalysis) 
 
12-lead ECG (in triplicate, approximately 1 minute apart) 
 
Serology 
 
Endocrinology 
 
Training in the use of subject questionnaires and IMP application 
 
AE review  
 
Prior and concomitant medications and procedures 
 
SEAR questionnaire (male subject and his female partner) 
 
PGI-S (male subject only) 
During the screening period (between site Visits 1 and 2), subjects and their partners are 
required to make a minimum of four attempts at sexual intercourse (without treatment) within 
a 4-week period at their convenience. The following assessments should be carried out during 
this time: 
 
SEP questionnaire (to be completed by the subject and his partner at home after each 
sexual intercourse attempt) 
 
Pre-screening IIEF questionnaire (i.e. IIEF-EF Question 1 to 5 and 15 only) to be 
completed by the subject at the end of the screening period on site, to confirm eligibility. 
Subjects who cannot comply with the minimum number of intercourse attempts or who exceed 
25 on the IIEF-EF will be excluded from the study before randomisation and dosing. 
11.1.3 
Double-Blind Phase: Treatment Period Assessments 
The following assessments should be carried out during the 12-week treatment period 
(including site Visits 2, 3, 4, and 5). 

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11.1.3.1 Day 1, Week 1 (Visit 2) 
At Site: 
Visit 2 must be attended by the male subject and his female partner. 
 
Eligibility check 
 
Medical history check 
 
Brief physical examination (focusing on any changes since screening) 
 
Repeated/reinforced training in the use of IMP application 
 
Urine pregnancy test (female partners of childbearing potential only) 
 
Randomisation 
 
Dispensing of medication supplies 
 
Vital signs (BP, HR, body temperature) 
 
AE review 
 
Concomitant medications monitoring 
 
IIEF questionnaire (male subject only) 
 
SEAR questionnaire (male subject and his female partner; can be completed by female 
partners at home if preferred) 
 
PGI-S (male subject only) 
11.1.3.2  Treatment Weeks 1–4 
At Home: 
 
Study drug administration 
 
SEP questionnaire (male subject and his female partner; after each sexual intercourse 
attempt) 
 
Onset and duration of action (erection) and erection hardness questions (male subject 
and his female partner; after each sexual intercourse attempt) 
 
AE completion and concomitant medication recording (using paper diaries) 
At Site (End of Week 4 1 week; Visit 3): 
Visit 3 must be attended by the male subject; attendance by his female partner is optional. 
 
Return of medication supplies (including visual inspection of IMP tubes) 
 
Repeated/reinforced training in the use of IMP application (if deemed necessary) 
 
Laboratory safety assessments (haematology, biochemistry and urinalysis) 
 
Vital signs (BP, HR, body temperature) 
 
IIEF questionnaire (male subject only) 
 
SEAR questionnaire (male subject and his female partner; can be completed by female 
partners at home if preferred) 
 
GAQ (male subject and his female partner; can be completed by female partners at home 
if preferred) 

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 
PGI-S (male subject only) 
 
PGI-C (male subject only)  
 
Dispensing of medication supplies 
 
AE review  
 
Concomitant medications monitoring 
11.1.3.3 Treatment Weeks 5–8 
At Home: 
 
Study drug administration 
 
SEP questionnaire (male subject and his female partner; after each sexual intercourse 
attempt) 
 
Onset and duration of action (erection) and erection hardness questions (male subject 
and his female partner; after each sexual intercourse attempt) 
 
AE completion and concomitant medication recording (using paper diaries) 
At Site (End of Week 8 1 week; Visit 4): 
Visit 4 must be attended by the male subject; attendance by his female partner is optional. 
 
Return of medication supplies (including visual inspection of IMP tubes) 
 
Repeated/reinforced training in the use of IMP application (if deemed necessary) 
 
Laboratory safety assessments (haematology, biochemistry and urinalysis) 
 
Vital signs (BP, HR, body temperature) 
 
IIEF questionnaire (male subject only) 
 
SEAR questionnaire (male subject and his female partner; can be completed by female 
partners at home if preferred) 
 
GAQ (male subject and his female partner; can be completed by female partners at home 
if preferred) 
 
PGI-S (male subjects only) 
 
PGI-C (male subjects only)  
 
Dispensing of medication supplies 
 
AE review  
 
Concomitant medications monitoring 

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11.1.3.4 Treatment Weeks 9–12 
At Home: 
 
Study drug administration 
 
SEP questionnaire (male subject and his female partner; after each sexual intercourse 
attempt) 
 
Onset and duration of action (erection) and erection hardness questions (male subject 
and his female partner; after each sexual intercourse attempt) 
 
AE completion and concomitant medication recording (using paper diaries) 
At Site (End of Week 12 1 week; Visit 5): 
Visit 5 must be attended by the male subject; attendance by his female partner is optional. 
 
Return of medication supplies (including visual inspection of IMP tubes) 
 
Full physical examination 
 
Laboratory safety assessments (haematology, biochemistry and urinalysis) 
 
Vital signs (BP, HR, body temperature) 
 
12-lead ECG (in triplicate, approximately 1 minute apart) 
 
IIEF questionnaire (male subjects only) 
 
SEAR questionnaire (male subject and his female partner; can be completed by female 
partners at home if preferred) 
 
GAQ (male subject and his female partner; can be completed by female partners at home 
if preferred) 
 
PGI-S (male subjects only) 
 
PGI-C (male subjects only) 
 
Usage and application questions 
 
AE review  
 
Concomitant medications monitoring 
11.1.4 
Double-Blind Phase: Follow-up Assessments (Visit 5 + 7 days [ 2 days]; 
Visit 6) 
Visit 6 must be attended by the male subject and his female partner. The following 
assessments should be carried out during the follow-up period, 7 days (± 2 days) after the 
Week 12 visit (Visit 5): 
 
Brief physical examination 
 
Urine pregnancy test (female partners of childbearing potential only; can be done at 
home if preferred) 
 
Vital signs (BP, HR, body temperature) 
 
AE review  
 
Concomitant medications monitoring  
 

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Following completion of these assessments, subjects may be invited to participate in the 
open-label extension phase of the study. See Section 11.1.5 for open-label extension phase 
assessments. 
11.1.5 
Open-Label Extension Phase Assessments 
At the end of the double-blind phase follow-up visit (Visit 6) subjects and their female partners 
who meet the eligibility criteria and consent to continue in the open-label extension phase of 
the study will be provided with medication supplies and repeated/reinforced training in the use 
of questionnaires and IMP application will be provided if required. 
11.1.5.1 Study Days 91–180 
At Home: 
 
Study drug administration 
 
SEP questionnaire (male subject only; after each sexual intercourse attempt) 
 
AE completion and concomitant medication recording (using paper diaries) 
At Site (Day 180  7 days; Visit 7): 
Visit 7 must be attended by the male subject; attendance by his female partner is optional. 
 
Brief physical examination (including a penis examination) 
 
Urine pregnancy test (female partners of childbearing potential only; can be done at 
home if preferred) 
 
Repeated/reinforced training in the use of IMP application (if deemed necessary) 
 
Dispensing of medication supplies 
 
Return of medication supplies (including visual inspection of IMP tubes) 
 
IIEF questionnaire (male subject only) 
 
Vital signs (BP, HR, body temperature) 
 
AE review  
 
Concomitant medications monitoring 
11.1.5.2 Study Days 181–270 
At Home: 
 
Study drug administration 
 
SEP questionnaire (male subject only; after each sexual intercourse attempt) 
 
AE completion and concomitant medication recording (using paper diaries) 
At Site (Day 270  7 days; Visit 8): 
Visit 8 must be attended by the male subject; attendance by his female partner is optional. 
 
Brief physical examination (including a penis examination) 
 
Urine pregnancy test (female partners of childbearing potential only; can be done at 
home if preferred) 

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 
Repeated/reinforced training in the use of IMP application (if deemed necessary) 
 
Dispensing of medication supplies 
 
Return of medication supplies (including visual inspection of IMP tubes) 
 
IIEF questionnaire (male subject only) 
 
Vital signs (BP, HR, body temperature) 
 
AE review  
 
Concomitant medications monitoring 
11.1.5.3 Study Days 271–360 
At Home: 
 
Study drug administration 
 
SEP questionnaire (male subject only; after each sexual intercourse attempt) 
 
AE completion and concomitant medication recording (using paper diaries) 
At Site (Day 360  7 days; Visit 9): 
Visit 9 must be attended by the male subject; attendance by his female partner is optional. 
 
Brief physical examination (including a penis examination) 
 
Repeated/reinforced training in the use of IMP application (if deemed necessary) 
 
Dispensing of medication supplies 
 
Return of medication supplies (including visual inspection of IMP tubes) 
 
IIEF questionnaire (male subject only) 
 
Vital signs (BP, HR, body temperature) 
 
AE review  
 
Concomitant medications monitoring 
11.1.5.4 Study Days 361–450 
At Home: 
 
Study drug administration 
 
SEP questionnaire (male subject only; after each sexual intercourse attempt) 
 
AE completion and concomitant medication recording (using paper diaries) 
At Site (Day 450  7 days; Visit 10): 
Visit 10 must be attended by the male subject; attendance by his female partner is optional. 
 
Brief physical examination (including a penis examination) 
 
Urine pregnancy test (female partners of childbearing potential only; can be done at 
home if preferred) 
 
Return of medication supplies (including visual inspection of IMP tubes) 
 
IIEF questionnaire (male subject only) 

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 
Vital signs (BP, HR, body temperature) 
 
12-lead ECG (in triplicate, approximately 1 minute apart) 
 
AE review  
 
Concomitant medications monitoring 
 
11.2 
Efficacy Assessments 
The efficacy of MED2005 will be assessed using the following subject-centred questionnaires 
at the time points described in the schedule of events (Table 1): 
 
The co-primary efficacy endpoints: 
- 
The IIEF-EF domain of the IIEF questionnaire, completed by the male subjects 
- 
Question 2 of the SEP questionnaire, completed by the male subjects 
- 
Question 3 of the SEP questionnaire, completed by the male subjects 
 
Secondary efficacy endpoints: 
- 
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 
The IIEF, PGI-S, PGI-C and usage and application questions will be completed by the male 
subjects only. The SEP, SEAR, GAQ and time of onset and duration of action (erection) and 
erection hardness questions will be completed by both the subject and his female partner. For 
further details, please refer to APPENDIX 1. 
11.2.1 
International Index for Erectile Function (IIEF) Questionnaire 
The IIEF was developed and validated in 1996–1997 as part of the sildenafil clinical study 
program [21] and in 1999, the IIEF was recommended by the 1st International Consultation on 
Erectile Dysfunction as the efficacy endpoint of choice for clinical studies in ED [22]. The IIEF 
has been validated, is widely used in numerous countries and has demonstrated specificity for 
detecting treatment-related changes in EF [23]. The IIEF consists of 15 questions divided into 
five domains of sexual function: EF (six questions), orgasmic function (two questions), sexual 
desire, (two questions), intercourse satisfaction (three questions) and overall satisfaction (two 
questions). A score of 0 to 5 is awarded to each of the 15 questions [21].  

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In this study, subjects will be asked to complete the IIEF at pre-screening, at the end of the 
screening period and at the end of each of the three 4-weekly periods during treatment in the 
double-blind phase (i.e. Visits 3, 4 and 5 [end of Weeks 4, 8 and 12]). The co-primary endpoint 
of this study will be the change from baseline (the end of the screening period) to the final on-
treatment visit (Visit 5, end of Week 12) in the IIEF-EF domain.  
During the open-label extension phase subjects will be asked to complete the IIEF to cover the 
previous 1 month period at Visits 7, 8, 9 and 10. 
Further details of the IIEF are provided in Section 18.1.  
11.2.2 
Sexual Encounter Profile (SEP) Questionnaire 
The SEP questionnaire consists of 5 items addressing the sexual events a subject experiences 
when attempting intercourse. The SEP questionnaire has been validated and is widely used in 
clinical studies as a measure of the efficacy of ED therapy. After each sexual encounter 
subjects will answer five yes or no questions in their SEP diary. Of particular interest will be 
Question 2: ‘Were you able to insert your penis into your partner’s vagina?’ and Question 3: 
‘Did your erection last long enough for you to have successful intercourse?’.  
In this study, subjects and their partners will be asked to complete the SEP questionnaire after 
each sexual intercourse attempt during the screening period (without treatment) and during 
each of the three 4-weekly periods during treatment in the double-blind phase (i.e. Weeks 1–
4, 5–8 and 9–12). Questions 2 and 3 of the SEP questionnaire will be co-primary efficacy 
endpoints along with the IIEF-EF. 
During the open-label extension phase male subjects will be asked to complete the SEP 
questionnaire after each sexual intercourse attempt. 
Further details of the male and female versions of the SEP questionnaire are provided in 
Section 18.2. 
11.2.3 
Self-Esteem And Relationship (SEAR) Questionnaire 
The SEAR questionnaire has strong psychometric properties that support its validity and 
reliability for measuring sexual relationship satisfaction, confidence and particularly 
self-esteem in men with ED [24]. An adapted SEAR questionnaire has also been shown to be 
a useful tool in women [25]. It consists of 14 items investigating two dimensions: sexual 
relationship satisfaction (8 items) and confidence (6 items; subdivided into self-esteem and 
overall relationship satisfaction). All items are scored on a 5-point Likert-type scale. A higher 
score signifies a more favourable response for all 14 items. 
In this study, subjects and their partners will be asked to complete the SEAR questionnaire at 
the end of the screening period and at the end of each of the three 4-weekly periods during 
treatment in the double-blind phase (i.e. Visits 3, 4 and 5 [end of Weeks 4, 8 and 12]). The 
SEAR questionnaire results will be part of the secondary efficacy endpoint analyses. Further 
details of the SEAR are provided in Section 18.3. 
11.2.4 
Global Assessment Questionnaire (GAQ) 
The GAQ allows the subject to rate (yes or no) the improvement in EF and has been used to 
assess efficacy outcomes after treatment with tadalafil in men with ED following spinal cord 
injury [26] and to evaluate the efficacy of udenafil for ED [27]. Subjects will complete GAQ 
Question 1 ‘Has the treatment you have been taking improved your erectile function?’ and if 

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necessary Question 2 ‘If yes, has the treatment improved your ability to engage in sexual 
activity?’. 
In this study, subjects and their partners will be asked to complete the GAQ at the end of each 
of the three 4-weekly periods during treatment in the double-blind phase (i.e. Visits 3, 4 and 5 
[end of Weeks 4, 8 and 12]). The GAQ results will be part of the secondary efficacy endpoint 
analyses. Further details of the male and female versions of the GAQ are provided in 
Section 18.4. 
11.2.5 
Patient Global Impression (PGI) Scales 
The global assessment tools the PGI-S and PGI-C were included to assess the subjects’ 
overall perception of their condition. The PGI-S and PGI-C are both 1-item questionnaires 
using balanced Likert scales that ask the subject to rate the severity of a specific condition (the 
PGI-S, a single-state 5-point categorical scale) or to rate at a particular timepoint the perceived 
change in his condition in response to treatment (the PGI-C, a transitional 7-point categorical 
scale). 
The PGI scales were modelled on the Clinical Global Impression scales developed in the 
1970s. They are simple, direct and easy to use and can be tailored to specific conditions and 
disease parameters. The PGI scales have previously been validated for use in a number of 
conditions including urinary incontinence and chronic pain [28, 29]. The PGI-C has also been 
validated for the evaluation of patient satisfaction (i.e. EF) after placement of a penile 
prosthesis [30]. 
In this study, subjects will be asked to complete the PGI-S at the end of Visit 1 and Visit 2, 
after completing the IIEF; and the PGI-S and PGI-C at the end of each of the three 4-weekly 
periods during treatment in the double-blind phase (i.e. Visits 3, 4 and 5 [end of Weeks 4, 8 
and 12]). The PGI results will be part of the secondary efficacy endpoint analyses. Further 
details of the PGI scales are provided in Section 18.5. 
11.2.6 
Onset and Duration of Action (Erection) and Erection Hardness 
Questions 
The subjects and their partners will be asked questions about the onset and duration of 
their/their partner’s erection and erection hardness in conjunction with the SEP after each 
sexual intercourse attempt during each of the three 4-weekly periods during treatment in the 
double-blind phase (i.e. Weeks 1–4, 5–8 and 9–12). Further details of the onset and duration 
of action (erection) and erection hardness questions are provided in Section 8. 
11.2.7 
Usage and Application 
 Questions on the usage and application of the gels will be completed once by the subject at 
the end of the treatment period in the double-blind phase (Visit 5): 
1. 
Who applied the gel most of the time? You/Your partner 
2. 
Did you/your partner find the tube easy to use? Yes/No 
3. 
Did you/your partner find the gel easy to apply? Yes/No 
4. 
Would you have preferred to use a different applicator such as a pad? Yes/No 
5. 
Did you incorporate the application of the gel as part of your foreplay? Yes/No 
6. 
Did 
you 
like 
using 
the 
gel? 
Liked 
a 
lot/Mostly 
liked/Neither 
liked 
or 
disliked/Disliked/Disliked a lot.   

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11.3 
Safety Assessments 
The sum total of these safety assessments listed in this section identifies the Princeton III “low 
risk subjects”. 
11.3.1 
Adverse events 
See Section 12 for full details of AE reporting and recording. 
11.3.2 
Physical Examination 
Subjects will receive a full physical examination at screening (Visit 1). Full physical 
examinations will include assessments of general appearance, skin, head and neck, lymph 
nodes, thyroid, abdomen, musculo-skeletal, cardiovascular, respiratory and neurological 
systems. The physical examination will also include a penis examination. Circumcision status 
will be recorded in the eCRF. Height, body weight and BMI will be calculated as part of the 
screening physical examination.  
Subjects will receive a brief physical examination that will focus on any changes since 
screening at Visits 2, 5 and 6 in the double-blind phase and at Visits 7, 8, 9 and 10 in the 
open-label extension phase. 
11.3.3 
Laboratory Safety Assessments 
Standard clinical laboratory safety assessments will be collected during screening and 
throughout the double-blind phase of the study. All laboratory safety assessments are 
detailed in Table 3 and described in detail below. 

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Table 3 
Laboratory Safety Variables 
Biochemistry 
Haematology 
Aspartate aminotransferase (AST) 
Haemoglobin 
Alanine aminotransferase (ALT） 
Haematocrit 
γ-glutamyl transpeptidase (GGT) 
Erythrocytes 
Alkaline phosphatase (ALP） 
Mean cell haemoglobin  
Total bilirubin (if > upper limit of normal [ULN] also 
direct and indirect bilirubin) 
Mean corpuscular haemoglobin concentration  
 
Cholesterol 
Mean corpuscular volume  
Triglycerides 
White blood cell count 
Creatine phosphokinase  
(Creatine Kinase [CK], and CK-Myocardial B if CK 
is elevated) 
Differential blood count, platelets 
Lactate dehydrogenase (LDH) 
Amylase (if > 1.5 × ULN, also pancreatic 
isoamylase) 
Erythrocyte sedimentation rate after 1 hour 
Creatinine 
Urinalysis 
Uric acid 
pH 
Urea 
Glucose 
Albumin 
Proteins 
Total protein 
Ketones 
Potassium  
Bilirubin 
Sodium  
Urobilinogen 
Calcium  
Nitrite 
Chloride  
Blood 
Glucose 
Leukocytes 
Inorganic phosphate (IP) 
Specific gravity 
C-reactive protein (CRP) 
Urine microscopy* 
Serology (at screening only) 
Urine Drugs of Abuse 
HIV-I and HIV-II antibodies 
Amphetamines 
HBsAG 
Barbiturates 
Hepatitis C virus (HCV) antibodies 
Benzodiazepines 
Hepatitis B core antibodies (HBc) (immunoglobulin 
G [IgG], and immunoglobulin M [IgM] if IgG is 
positive) 
Cannabinoids 
Endocrinology 
Opiates 
Testosterone  
Cocaine 
 
Methadone 
 
Tricyclic antidepressants 
* If deemed necessary, based on a clinically significant positive urinalysis test, microscopic examination of sediment and/or 
culture will be performed. 

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11.3.3.1 Haematology and Biochemistry 
Blood samples for determination of haematology and biochemistry safety variables will be 
taken at screening (Visit 1) and at the end of each of the three 4-weekly periods during 
treatment in the double-blind phase (i.e. Visits 3, 4 and 5 [end of Weeks 4, 8 and 12]). 
The date and time of collection will be recorded on the appropriate eCRF. The analyses will 
be done at a central laboratory using routine methods. 
Clinical laboratory values outside the reference limits, which are suspected to be of any clinical 
significance, will be repeated. Subjects with suspected clinically significant results confirmed 
on repeated sampling should not be included in the study; or, if the subject is already included, 
they should be followed until test normalisation or for as long as the PI considers necessary. 
11.3.3.2 Urinalysis 
Urine samples for determination of urinalysis safety variables will be taken at screening (Visit 1) 
and at the end of each of the three 4-weekly periods during treatment in the double-blind phase 
(i.e. Visits 3, 4 and 5 [end of Weeks 4, 8 and 12]). Urinalysis will be performed by the site using 
a dipstick method. 
11.3.3.3 Serology 
All subjects will be tested for HBsAG, HCV antibodies, HBc antibodies and HIV-1 and HIV-2 
antibodies at screening (Visit 1). This is done for the safety of the study personnel. If a subject 
has a positive result from any of these tests, he will be referred for further examination and 
treatment and will not be included in the study. These samples will be analysed by a central 
laboratory. 
11.3.3.4 Endocrinology 
Morning testosterone samples will be taken for the male subjects at screening (Visit 1). If the 
reading is below the laboratory normal range the test should be repeated using an early 
morning specimen. Repeated low levels indicate the possibility of hypogonadism and the 
subject should be referred for full investigation and not recruited. 
11.3.3.5 Urine Drugs of Abuse 
Urine samples will be tested for drugs of abuse by the site at screening (Visit 1). If a subject 
fails the drugs of abuse screen they will be excluded from the study. A repeat drug screen can 
only be done when methodological reasons are believed to have led to a false positive. 
Borderline positive results, unless covered by the preceding condition, are to be considered as 
positive and the subject will be excluded from the study. If a subject is found to be positive due 
to medication; e.g. flu/cold remedies, any medication containing an opioid, they may undergo 
a repeat drug screen if they are still within the screening window. 
11.3.3.6 Alcohol Breath Test 
An alcohol breath test will be carried out at screening (Visit 1), using an alcometer.  
11.3.3.7 Urine Pregnancy Test 
During the double-blind phase, female partners of childbearing potential will be required to 
perform a urine pregnancy test on Day 1 of the treatment period (Visit 2; at the study site) and 
at the follow-up visit (Visit 6; at the study site or at the subject’s home if preferred [photographs 
of a negative urine pregnancy test will be accepted]).  

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During the open-label extension phase, female partners of childbearing potential will be 
required to perform a urine pregnancy test on Day 180 ( 7 days), Day 270 ( 7 days), Day 360 
( 7 days) and Day 450 ( 7 days). The pregnancy test may be performed at the study site or 
at the subject’s home if preferred (photographs of a negative urine pregnancy test will be 
accepted).  
Additional urine pregnancy tests may be performed at the PI’s discretion.  
The pregnancy test kit will be provided. 
11.3.4 
Vital Signs 
11.3.4.1 Blood Pressure and Heart Rate 
Supine and standing BP and HR will be measured at screening (Visit 1), during the 
double-blind phase on Day 1 of the treatment period (Visit 2), at the end of each of the three 
4-weekly periods during treatment (i.e. Visits 3, 4 and 5 [end of Weeks 4, 8 and 12]) and at the 
follow-up visit (Visit 6), and during the open-label extension phase at Visits 7, 8, 9 and 10. For 
supine vital signs measurements, subjects will be required to rest in a supine position for at 
least 10 minutes prior to their measurements. Standing vital signs measurements will then be 
taken after 1 minute of standing. 
11.3.4.2 Body Temperature 
Body temperature (tympanic) will be measured (a single measurement) in degrees Celsius 
using an automated thermometer at screening (Visit 1), during the double-blind phase on 
Day 1 of the treatment period (Visit 2), at the end of each of the three 4-weekly periods during 
treatment (i.e. Visits 3, 4 and 5 [end of Weeks 4, 8 and 12]) and at the follow-up visit (Visit 6), 
and during the open-label extension phase at Visits 7, 8, 9 and 10.  
11.3.5 
12-lead ECGs 
12-lead ECGs will be recorded at screening (Visit 1), at the end of the final treatment period in 
the double-blind phase (Visit 5, end of Week 12) and in the open-label extension phase on 
Day 450 (Visit 10).  
ECG recordings will be made after the subject has been resting in a supine position for at least 
10 minutes. The subjects should avoid postural changes during the ECG recordings and 
clinical staff will ensure that subjects are awake during the recording. At each time point, the 
ECG will be recorded in triplicate. The triplicates will be performed at approximately 1 minute 
intervals.  
ECG printouts may be filed in the subject’s eCRF for medical safety reviews. If possible, the 
same recorder will be used for any one subject. Each ECG recorder will be set up to the 
required technical specifications and containing the information required to identify the records. 
Each ECG recording will be clearly identified (with Subject ID, scheduled time relative to dose, 
and the actual time of ECG recording). All recorded ECGs will be reviewed by a PI or Sub-
Investigator and documented in the eCRF. If a subject shows an abnormal ECG at any stage 
during the study, additional safety recordings (including the use of 5- or 12-lead Holter 
equipment) may be made and the abnormality followed to resolution if required. The PI should 
ensure all relevant staff are fully trained in carrying out ECG recordings. 

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11.4 
Other Assessments 
11.4.1 
Informed Consent 
Informed consent will be signed by both partners during screening (Visit 1) before they can be 
admitted into the study. To continue into the open-label extension phase, informed consent 
must be signed by both partners at Visit 6. 
11.4.2 
Eligibility 
Eligibility will be assessed at pre-screening and screening (Visit 1) and then confirmed on 
Day 1 of the treatment period in the double-blind phase (Visit 2). 
Eligibility will include the IIEF questionnaire (completed pre-screening for eligibility of the 
subject to enter the main screening period and at the end of the screening period to confirm 
eligibility for randomisation and dosing) and ED history. Subjects with less than four attempts 
at sexual intercourse or high IIEF scores (> 25) during the screening period will be excluded 
prior to entry into the treatment period. 
Eligibility to participate in the open-label extension phase will be assessed at the follow-up visit 
(Visit 6) after completion of the assessments in the double-blind phase and will be subject to 
availability of places. 
11.4.3 
Medical History 
Medical history will be checked and recorded at screening (Visit 1) and on Day 1 of the 
treatment period in the double-blind phase (Visit 2). Medical history will include history of ED 
and surgical history. 
11.4.4 
Volume of Blood Sampling 
The maximum blood volume will not exceed 50 mL per subject during the study. 
11.4.5 
Training 
Efficacy Questionnaires 
Subjects will be trained in the use of the efficacy questionnaires at screening (Visit 1). The 
training will be repeated/reinforced on Day 1 of the treatment period in the double-blind phase 
(Visit 2). 
IMP Application 
Subjects and their female partners will be trained in the application of the IMP at screening 
(Visit 1). The training will be repeated/reinforced during the double-blind phase on Day 1 of the 
treatment period (Visit 2), and if deemed necessary also at Visits 3, 4 and 5 (i.e. if the 
investigator thinks the subject/partner needs re-training on expressing a dose after visual 
inspection of previously used IMP tubes to check if the tube has been pierced). Training will 
be repeated/reinforced during the open-label extension period if required. 
Training will be conducted using a model of a phallus and will describe the method required 
for both circumcised and non-circumcised men. An assessment of physical capability will also 
be conducted and application training tailored to their needs. 
The couple will be instructed on how to operate the aluminium tubes, how to apply the single 
dose of MED2005 to the glans penis (by the man or the woman) and the length of time it should 

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be rubbed in prior to sexual intercourse (at least 15 seconds). A description and diagram of 
this process will be supplied to the subjects in the application instructions. Subjects will also 
be asked to avoid oral stimulation of the penis for at least 5 minutes post application and 
reminded to return all drug materials for accountability. 
12. 
ADVERSE EVENTS 
AEs will be monitored throughout the duration of the study from signing of the ICF at screening 
(Visit 1) until the final study visit. Study site personnel will report any AE, whether observed by 
the investigator or reported by the subject. 
12.1 
Adverse Events 
12.1.1 
Definitions 
The definitions of AEs, adverse drug reactions (ADRs), SAEs and suspected unexpected 
serious adverse reactions (SUSARs) are given below. It is of the utmost importance that all 
staff involved in the conduct of clinical research are familiar with the contents of this section. 
Adverse Event 
An AE is any untoward medical occurrence (including the deterioration of a pre-existing 
medical condition) in a patient or clinical investigation subject administered a pharmaceutical 
product and which does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding, for example), symptom or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. In clinical 
studies, an AE can include an undesirable medical occurrence occurring at any time, from the 
date informed consent was signed until the end of their participation in a study; i.e. the subject 
has discontinued or completed the study. 
The causality of AEs (i.e. their relationship to study treatment) will be assessed by the PI who, 
in completing the relevant eCRF, must answer ‘yes’ or ‘no’ to the question: ‘Do you consider 
that there is a reasonable possibility that the event may have been caused by the study 
medication?’.  
The following factors should be considered when deciding if there is a ‘reasonable possibility’ 
that an AE may have been caused by the study medication (that is, there are facts/evidence 
or arguments to suggest a causal relationship): 
 
Time course and exposure to suspect drug: Has the subject or their female partner 
actually received the suspect drug? Does the AE have a reasonable temporal 
relationship to the administration of the suspect drug? 
 
Consistency with known drug profile: Is the AE consistent with previous knowledge of 
the suspect drug (pharmacology and toxicology) or drugs of the same pharmacological 
class? OR, could the AE be anticipated from its pharmacological properties? 
 
No alternative cause: The AE cannot be reasonably explained by another aetiology such 
as the underlying disease, other drugs, other host or environmental factors 
 
Laboratory tests: A specific laboratory investigation (if performed) has confirmed the 
relationship? 
A ‘reasonable possibility’ could be considered to exist for an AE where one or more of these 
factors exist.  

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In difficult cases, other factors could be considered such as: 
 
Is this a recognised feature of the drug? 
 
Is there a known mechanism? 
Ambiguous cases should be considered as being a ‘reasonable possibility’ of a causal 
relationship unless further evidence becomes available to refute this.  
Adverse Drug Reaction 
An ADR is any AE where a causal relationship with the IMP is at least a reasonable possibility; 
i.e. the relationship cannot be ruled out. 
Serious Adverse Event  
An SAE is an AE occurring during any study period (i.e. screening, treatment and follow-up, 
open-label extension), and at any dose of the investigational product or placebo, that fulfils 
one or more of the following criteria: 
 
Results in death 
 
Is immediately life-threatening 
 
Requires in-patient hospitalisation or prolongation of existing hospitalisation 
 
Results in persistent or significant disability or incapacity 
 
Is a congenital abnormality or birth defect 
 
Is an important medical event that may jeopardise the subject or may require medical 
intervention to prevent one of the outcomes listed above 
The causality of SAEs; i.e. their relationship to study treatment, will be assessed in the same 
way as for non-serious AEs. 
Note that SAEs that could be associated with any study procedure should also be reported. 
Suspected Unexpected Serious Adverse Reactions 
A SUSAR is any SAE where a causal relationship with the IMP is at least a reasonable 
possibility, but is not listed in the ‘Reference Safety Information’ section (Section 7) of the IB. 
12.1.2 
Recording of Adverse Events 
AEs will be collected from the signing of the ICF at screening (Visit 1) until the end of the study. 
Any AEs that are unresolved at the subject's last AE assessment during the study (i.e. at the 
subject’s final study visit) are to be followed-up by the PI for as long as medically indicated, but 
without further recording in the eCRF. FMD retains the right to request additional information 
for any subject and/or their female partner with ongoing AE(s)/SAE(s) at the end of the study, 
if judged necessary. 
Subjects and their partners will be monitored for AEs by being asked to complete paper diaries 
of untoward signs and symptoms as they experience them (i.e. in real time) throughout the 
duration of the study. The diaries will be reviewed at study visits and AEs entered into the 
eCRF. If preferred, the AEs for female partners can be followed up by telephone. 

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AEs spontaneously reported by the subject or their female partner and/or in response to an 
open question ‘Have you had any health problems during the study day/since your previous 
visit?’ from the study personnel, or revealed by observation, will be recorded during site visits 
throughout the study. 
Findings and values related to physical examinations and measurements of ECG, vital signs, 
(BP, HR, temperature) and laboratory variables will be defined as AEs if they are considered 
clinically relevant deteriorations compared with baseline and pre-dose values, as judged by 
the PI. 
12.1.3 
Assessment of Adverse Events 
12.1.3.1 Adverse Event Intensity 
The following variables will be recorded for each AE: Onset, resolution, maximum intensity, 
action taken, outcome, causality (yes or no) and whether it constitutes an SAE or not. 
The intensity rating is defined as: 
 
Mild (awareness of sign or symptom, but easily tolerated) 
 
Moderate (discomfort sufficient to cause interference with normal activities) 
 
Severe (incapacitating, with inability to perform normal activities) 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
(as in mild, moderate or severe) whereas seriousness is defined by the criteria in 
Section 12.1.1 (i.e. it is based on subject/event outcome or action criteria usually associated 
with events that pose a threat to a subject’s life or functioning). An AE of severe intensity will 
not necessarily meet the criteria for an SAE. For example, nausea that persists for several 
hours may be considered severe nausea, but is not an SAE. On the other hand, a stroke that 
results in only a limited degree of disability may be considered a mild stroke but would be 
classified as an SAE. 
In case of an overdose (accidental or deliberate), all symptoms associated with it should be 
reported as AEs.  
12.1.3.2 Adverse Event Causality 
For each AE one of the following categories will be selected based on medical judgement, 
consideration of the definitions below and all contributing factors.  
ADR-related 
Related 
A clinical event, including a clinically significant abnormal laboratory test or other 
measurement, which occurs in a plausible time relationship to study drug administration, and 
which concurrent disease or other drugs or chemicals cannot explain. 
Probably related 
A clinical event, including a clinically significant abnormal laboratory test or other 
measurement, with a reasonable time sequence to study drug administration, and is unlikely 
to be attributed to concurrent disease or other drugs or chemicals. 

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Possibly related 
A clinical event, including a clinically significant abnormal laboratory test or other 
measurement, with a reasonable time sequence to study drug administration, but which could 
also be explained by concurrent disease or other drugs or chemicals. Information on drug 
withdrawal may be lacking or unclear.  
Non-ADR-related 
Unrelated 
A clinical event, including a clinically significant abnormal laboratory test or other 
measurement, with little or no temporal relationship with study drug administration. Typically 
explained by extraneous factors (e.g. concomitant disease, environmental factors or other 
drugs or chemicals).  
12.1.3.3 Outcome 
The PI or their delegate will follow up all AEs wherever possible until the symptom has resolved 
or stabilised.  
The date of confirming outcome will be recorded. The course of AEs will be assessed using 
the following outcomes as a guide: 
1. 
Recovered: The AE has resolved and the subject returned to his/her condition prior to 
onset 
2. 
Recovering: The AE has almost resolved and the subject is returning to his/her condition 
prior to onset 
3. 
Not recovered: Even on the final day of observation, the AE had not resolved and the 
subject’s condition remained unchanged. In case of death, the subject died of other 
causes not related to the AE from which there was no recovery 
4. 
Recovered with sequelae: The AE resolved, but the subject has sequelae 
5. 
Fatal: The subject died.  
6. 
Unknown: The AE could not be categorised as per above 
12.1.4 
Reporting of Serious AEs  
If any SAE/SUSAR occurs, the PI will take appropriate action immediately and will strive to 
identify the cause(s) of the event(s). 
Any SAE will be notified by the PI to the Pharmacovigilance Service Provider and Study 
Monitor designated by the Sponsor within 24 hours by email or fax. 
Assessment of causality (relatedness) and seriousness will be made by the site Physician. The 
FMD Medical Advisor will not be able to downgrade the opinion of the site Physician with 
regards to causality or seriousness. Assessment of expectedness of the SAE will be conducted 
by the FMD Medical Advisor with reference to the ‘Reference Safety Information’ section 
(Section 7) of the IB. 
The initial report will be followed up by a full written report within three working days or five 
calendar days, whichever comes first, unless no further information is available. A follow-up 
report and any subsequent reports will be provided as soon as possible when new information 
becomes available. Occurrence of SUSARs will be notified to the Regulatory Authority by the 

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Pharmacovigilance Service Provider or their delegate within 7 days (for fatal and 
life-threatening SUSARs) or 15 days (for all other SUSARs).  
SAEs/SUSARs must be recorded and reported whether or not the PI considers the 
SAE/SUSAR to be related to the IMP. 
Photocopies of results, consultant report(s), a summary of the outcome of the reaction and the 
PI's opinion of the IMP’s relationship to the SAE/SUSAR will accompany the SAE form if and 
when available.  
12.1.1 
Reporting and Follow-Up of Pregnancy  
Any pregnancy in the female partner will be notified by the PI to the Pharmacovigilance Service 
Provider and Study Monitor designated by the Sponsor within 24 hours by email or fax. 
Pregnancy will be followed to outcome. 

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13. 
QUALITY ASSURANCE AND QUALITY CONTROL 
13.1 
Quality Assurance and Quality Control 
To ensure GCP compliance and compliance with all applicable regulatory requirements, the 
Sponsor or site may conduct a quality assurance (QA) audit. A regulatory inspection of this 
study may be carried out by regulatory agencies. Such audits/inspections can occur at any 
time during or after completion of the study. If an audit or inspection occurs, the PI and the site 
will agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
their time and the time of their staff to the auditor/inspector to discuss any findings or relevant 
issues. Quality control (QC) procedures at the site will be implemented to ensure data recorded 
into the eCRFs are accurate before eCRFs are sent for data entry purposes.  
13.2 
Monitoring 
During the study, a person designated by FMD will have regular contact with the study sites, 
including visits to: 
 
Provide information and support to the PI 
 
Confirm that facilities remain acceptable 
 
Confirm that the investigational team is adhering to the protocol, that data are being 
accurately and timely recorded in the eCRFs, that biological samples are handled 
appropriately and that IMP accountability checks are being performed 
 
Perform source data verification (a comparison of the data in the eCRFs with the 
subject’s medical records at the hospital or practice, and other records relevant to the 
study) including verification of informed consent of participating subjects. This will require 
direct access to all original records for each subject (e.g. clinic charts) 
 
Ensure withdrawal of informed consent to the use of the subject’s biological samples is 
reported and biological samples are identified and disposed of/destroyed accordingly, 
and the action is documented and reported to the subject 
The FMD Clinical Project Manager will be available between visits if the PI, or other staff at the 
site, need information and advice about the study conduct. 
13.3 
Blinded Review Meeting 
Once all subjects have completed Visit 6 and after discrepancy management and critical QC 
of the data are complete and before database lock for the double-blind phase, a blinded review 
of the study data will be performed to identify minor and major protocol deviations. In particular, 
in this meeting, subjects (and/or specific data) to be excluded from the per protocol (PP) set 
will be identified. 
Once all subjects have completed the open-label extension phase and after discrepancy 
management and critical QC of the data are complete and before database lock for the 
open-label extension phase, a review of the study data will be performed to identify minor and 
major protocol deviations. 

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14. 
STATISTICAL ANALYSES 
Further details of the proposed statistical analysis will be documented in the statistical analysis 
plan (SAP), which will be written following completion of the protocol and finalised prior to the 
breaking of the blind. 
In general, safety and efficacy variables will be presented by means of descriptive statistics 
and figures, as appropriate, by treatment (active at each dose level and placebo) and by time 
point and gender, if applicable. Continuous variables will be summarised using the number of 
non-missing observations, mean, standard deviation (SD), median, first and third quartiles, 
minimum and maximum. Categorical variables will be presented using number of subjects and 
percentages. For ordered categorical variables, cumulative percentages may also be 
presented. Raw data will be listed. 
Baseline values will be the last assessments prior to randomisation at Visit 2 unless stated 
otherwise. 
A Bonferroni correction will be used to take into account that there are three active versus 
placebo comparisons; i.e. all p-values resulting from comparing the three different MED2005 
doses (0.6 mg GTN, 1.2 mg GTN, 1.8 mg GTN) versus placebo will be multiplied by three and 
statistical significance will then be declared if p < 0.05. Corresponding Bonferroni corrected 
95% confidence intervals will be produced. 
The objective for the double-blind phase is for all co-primary endpoints to show superiority of 
MED2005 to placebo in order to conclude a significant result of the study. For this objective, 
no adjustment for multiplicity of the error probability for the individual co-primary endpoints is 
required. However, the three co-primary endpoints will still be considered in a hierarchy of their 
importance, with the testing order being IIEF-EF domain, SEP Question 3 and SEP 
Question 2. 
The objective of the open-label extension phase is to evaluate the safety of long-term (up to 
12 months) use of MED2005. In addition, the long-term efficacy of MED2005 will be evaluated. 
Both safety and efficacy will be evaluated in the subset of subjects who completed the 
double-blind phase and took part in the open-label extension phase. Descriptive statistics will 
be based on observed data. In case of any randomisation/treatment errors, any summaries 
split by treatment group will be produced according to treatment received. 
Once all subjects have completed the double-blind phase (Visit 6), the database will be locked, 
treatment groups unblinded and the analysis of the double-blind phase will be performed using 
all data from the screening and double-blind treatment phases. A second analysis will be 
performed once all applicable subjects have completed the open-label extension phase.  
14.1 
Analysis Sets 
The following analysis sets will be used for the statistical analysis of the double-blind phase: 
 
The randomised set will consist of all subjects who were randomised to a treatment 
 
The safety set will consist of all subjects in the randomised set who made use of the 
medication at least once. In the case of randomisation/treatment errors, subjects will be 
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 
The full analysis set (FAS) will consist of all subjects in the randomised set who made 
use of the medication at least once. In the case of randomisation/treatment errors, 
subjects will be analysed according to randomised treatment  
Primary and secondary analyses will be performed on the FAS. 
 
The per protocol set (PP) will consist of all subjects in the FAS who completed the 
12-week treatment period without major protocol violations and who have valid IIEF, SEP 
Question 2 and SEP Question 3 assessments at Week 12 (Visit 5) 
Analysis sets will be identified prior to the unblinding of the study data. The efficacy analysis 
will be performed as randomised; i.e. a subject will be assigned to the treatment he was initially 
allocated, irrespective of what treatment was actually applied, and whether or not treatment 
was discontinued while questionnaire data was collected (see Section 9.6 Withdrawal of 
Subjects). 
In order to assess the consistency of results, sub-group analyses will also be performed 
according to three subject baseline ED severity groups:  
 
Mild (IIEF-EF domain score of 17–25)  
 
Moderate (IIEF-EF domain of 11–16) 
 
Severe (IIEF-EF domain of ≤ 10) 
 
The following analysis set will be used for the statistical analysis of the open-label extension 
phase: 
 
The open-label analysis set (OLAS) will consist of all subjects who made use of 
medication at least once during the open-label extension.  
 
14.2 
Demographic and Baseline Measurements 
Assessments made at screening and at baseline of the treatment period will be summarised 
overall and for each treatment group. These assessments will include demographic and other 
relevant baseline characteristics (such as medical history, physical examination and the 
assessments made during the screening period). There will be no formal comparison of 
baseline data; that is, no statistical hypothesis testing. 
14.3 
Prior and Concomitant Medication 
Prior and concomitant medication will be summarised overall and by treatment. For further 
information, please also refer to Section 10.5.  
14.4 
Number of Intercourse Attempts 
Use of study medication and number of intercourse attempts will be summarised by treatment 
and 4-week period. Mean and median number of intercourse attempts will be given as well as 
an absolute and relative number of subjects tabulated by number of intercourse attempts. 

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14.5 
Efficacy Evaluation 
14.5.1 
Efficacy Measures 
For a list of efficacy assessments, see Section 11.2. 
Summary statistics for all efficacy measures will be given by treatment, 4-week period (double-
blind phase) and 3-month period (open-label extension phase) and gender (where applicable), 
for actual values and changes from baseline. Individual components of composite scores (but 
not domains) will not be summarised unless otherwise stated. Individual components as well 
as domains will be presented in listings together with the scores used in the analysis.  
The co-primary efficacy outcomes will be change from baseline to 12 weeks of treatment in 
the IIEF-EF domain, SEP Question 2 and SEP Question 3 at Week 12.  
Listings and summary statistics for the IIEF-EF, SEP Question 2 and SEP Question 3 will also 
be provided for the subsets in the open-label extension phase of the study. 
14.5.2 
Handling of Missing Values 
Full details on the handling of missing values in analyses of all analysis sets, including rules 
applied to incomplete questionnaires and planned additional analyses, will be defined in the 
SAP. Only the main principles are given for the analyses on the FAS here.  
 
Summary statistics will present the number of missing values and then will be based on 
non-missing values.  
Any missing values in efficacy questionnaire data that occur during the treatment period and 
are then followed by observed data shall be treated as missing at random and imputed using 
a corresponding multiple imputation approach. 
All subjects who are withdrawn from the study will be asked to continue with the IIEF and SEP 
questionnaires if possible. These data will be used as part of the analysis for estimating the 
treatment effect over 12 weeks, according to the randomised treatment policy. 
There can be remaining missing values for the primary endpoints for subjects who leave the 
study and provide no further questionnaire data. For these subjects, missing values will be 
handled using a control-based multiple imputation approach. The imputation model for the 
missing observations in both the MED2005 and placebo (control) groups will be constructed 
from the control group only (missing not at random [MNAR]). This assumes that efficacy results 
post withdrawal, for subjects who withdraw, would have mirrored those seen in the placebo 
group and thus lose any potential MED2005 treatment benefit.  
Additional estimands/tests of treatment effect, beyond the primary treatment policy estimand, 
may be addressed, including exploring other ways of handling missing values, such as fitting 
repeated measures mixed models.  
Summary statistics will present the number of observed values and will then be based on the 
non-missing values for the open-label extension phase. 
 

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14.5.3 
Primary Analysis 
The co-primary efficacy endpoints, assessed in the male subjects, are: 
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 
Baseline for the IIEF-EF score is the assessment at Visit 2, baseline for SEP Questions 2 and 
3 is the percentage in the screening, treatment free, 4-week period. 
The primary objective will be assessed by testing the following hypotheses for each MED2005 
dose group (0.6 mg GTN, 1.2 mg GTN or 1.8 mg GTN) and each co-primary endpoint 
separately, using the FAS: 
Null hypothesis (H0): There is no difference in the mean change from baseline in the IIEF-EF 
domain, SEP Question 2 and SEP Question 3 for the MED2005 treatment group compared 
with placebo. 
H0: μ (MED2005) = μ (placebo) 
Alternative hypothesis (H1): There is a difference in the mean change from baseline in the 
IIEF-EF domain, SEP Question 2 and SEP Question 3 for the MED2005 treatment group 
compared with placebo. 
H1: μ (active) ≠ μ (placebo) 
Each comparison will be carried out at the two-sided 5% level of statistical significance after a 
Bonferroni correction (p-values multiplied by three). Efficacy will be stated if all null hypotheses 
for the co-primary endpoints are rejected. However, the three co-primary endpoints will still be 
considered in a hierarchy of their importance, with the testing order being IIEF-EF domain, 
SEP Question 3 and SEP Question 2. 
The statistical model for the primary analysis of the IIEF-EF will be an analysis of covariance 
(ANCOVA) including terms for treatment group, site and baseline (as a continuous variable). 
The statistical model for the primary analyses of SEP Question 2 and SEP Question 3 will be 
an ANCOVA including terms for treatment group, site, baseline (as a continuous variable) and 
baseline ED severity (categorical variable). As the endpoints are change from baseline 
assessment, the respective baselines for each endpoint are included in the analyses. Baseline 
ED severity, used as part of the randomisation scheme, is a categorical grouping of the 
baseline IIEF-EF and as such is not included in the primary analysis of the IIEF-EF as it already 
appears in the model as a continuous variable. A sensitivity analysis will be performed 
including baseline ED severity (categorical variable) in addition to the variables included in the 
primary analysis. The estimated treatment means and differences (MED2005 versus placebo) 
will be reported as part of this analysis.  

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14.5.4 
Other Efficacy Variables 
All other efficacy variables will be analysed in a supportive way to describe the effect of 
treatment. Secondary analyses will also be performed on the FAS and with the ANCOVA 
approach. 
Double-blind phase: 
The following secondary efficacy analyses will be conducted: 
 
The analysis of the three co-primary endpoints will be repeated in the three pre-specified 
subgroups of ED severity: mild, moderate and severe as specified in Section 14.1 
 
The change in the IIEF-EF domain, SEP Question 2 and SEP Question 3 at each 4-week 
visit will be analysed 
 
Responder analyses assessing the proportion of subjects with a specific increase in the 
IIEF-EF domain from baseline, using a different responder definition defined separately 
for each baseline severity group, will be conducted. A responder is defined as having an 
increase of ≥ 2, ≥ 5 and ≥ 7 for the mild, moderate and severe subjects, respectively 
(published Minimal Clinically Important Difference [MCID] according to Rosen et al. 2011 
[31]) 
 
Responder analyses for SEP Questions 2 and 3 will be conducted in the same way as 
for the IIEF-EF. A responder is defined as having an increase of –1.3%, 16.7% and 
27.3% for SEP Question 2 and 5.0%, 23.3% and 17.0% for SEP Question 3 for patients 
with mild, moderate and severe baseline ED, respectively (published MCID according to 
Araujo et al. 2012 [32]) 
 
Responder analyses will also be conducted using responder thresholds (that represent 
meaningful within-patient changes) in the three co-primary endpoints that are determined 
using a suitable set of data from this study, prior to study unblinding. Receiver operating 
characteristics (ROC) analyses will be performed to define the thresholds using the 
PGI-S and PGI-C as anchors, with the thresholds chosen to balance sensitivity and 
specificity, supplemented with both empirical cumulative distribution functions and 
probability density functions. The thresholds defined from these analyses will be included 
in the final SAP prior to breaking the blind. 
The following secondary efficacy analyses will be conducted in a more exploratory way making 
use of the FAS data in the selected doses and placebo over both stages: 
 
The GAQ will be analysed via logistic regression including terms for treatment group, site 
and baseline ED severity (categorical variable)  
 
The change in the other domains of the IIEF questionnaire, the other SEP questions 
(Questions 1, 4 and 5), the overall SEAR questionnaire score, the scores in the two 
subdomains of the SEAR questionnaire (sexual relationship satisfaction and confidence) 
and the PGI-S at time points 4, 8 and 12 weeks will be analysed using ANCOVA as 
described for the primary endpoint analysis for SEP Questions 2 and 3. The PGI-C will 
be analysed using an analysis of variance (ANOVA) 
 
Subjective measures of the time of onset and duration of action (erection) and erection 
hardness will be analysed using Wilcoxon ranks for each intercourse attempt, averaged 
across intercourse attempts within each 4-week period for each subject. The averaged 
Wilcoxon rank data will be analysed using ANCOVA as described for the primary 
endpoint analysis 

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 
Usage and application question responses will be summarised by treatment group 
All efficacy assessments provided by the female partners will be analysed using the same 
statistical models as for the male subjects. 
Opel-label extension phase: 
Summary statistics for all efficacy measures will be given for actual values and changes from 
baseline (where applicable), where the baseline assessments are the ones prior to the double-
blind phase. Individual components of composite scores (but not domains) will not be 
summarised unless otherwise stated. Individual components as well as domains will be 
presented in listings together with the scores used in the analysis.  
Summaries of responders at each Visit will be given using the same responder definitions as 
per the analysis of double-blind phase. 
14.6 
Evaluation of Safety 
Safety assessments will include physical examinations, vital signs (BP, HR, body 
temperature), standard clinical laboratory safety tests (haematology, biochemistry, urinalysis), 
12-lead ECGs and monitoring of AEs pre- and post-treatment. Safety analysis will be based 
on the safety set for the double-blind phase and the OLAS for the open-label extension phase. 
Missing values will not be imputed. 
Dosing duration and frequency will be summarised. 
14.6.1 
Vital Signs 
Vital signs will be summarised for each treatment group by visit. Summary statistics will be 
provided for actual values and change from baseline, where the baseline value is the last value 
prior to dosing. 
14.6.2 
Clinical Laboratory Safety Tests 
The results of clinical laboratory tests and change from baseline will be summarised for each 
treatment group by visit, where the baseline value is the last value prior to dosing. Values 
outside the normal ranges will be flagged and summarised. 
14.6.3 
ECGs  
ECGs will be summarised for each treatment group by visit. Summary statistics will be provided 
for actual values (based on the mean of the triplicate readings for each subject) and change 
from baseline, where the baseline is defined as the mean of the values recorded at the 
screening (Visit 1) ECG. 
14.6.4 
Adverse Events  
All AEs will be listed by system organ class (SOC) and preferred term (PT) classifications 
assigned to the event using the Medical Dictionary for Regulatory Activities (MedDRA) 
(Version 20.1 or higher). The number of AEs and number (and %) of subjects with AEs will be 
summarised by SOC and PT. In addition, AEs will be summarised by severity, relationship to 
treatment, time to onset (following the last dose of IMP prior to AE start date) and duration 
(offset).  
Listings will be presented for SAEs and AEs leading to withdrawal.  

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14.7 
Sample Size 
A sample size of n = 250 per group (total N = 1000) provides 90% study power to reject the 
null hypotheses for all three primary endpoints when comparing a MED2005 dose to placebo, 
using a Bonferroni corrected type I error, adjusting for three dose versus placebo comparisons. 
The sample size calculations were performed using EAST 6.4 in the continuous endpoint 
two-sample multiple comparisons multiple endpoints platform using the assumptions described 
below.  
It is assumed that MED2005 is slightly better than alprostadil [33]. For the higher two doses 
alprostadil saw an improvement compared to placebo for IIEF-EF of 3.2 and 3.1 (least squares 
[LS] mean changes), giving an average of 3.15, for SEP Question 2 of 9.6 and 11.3 (LS mean 
changes), giving an average of 10.65, and for SEP Question 3 of 13.4 and 8.7 (LS mean 
changes), giving an average of 11.05. In Study FM53 there was a better improvement in SEP 
Question 3 than SEP Question 2 so the sample size assumptions take this into account. PDE 
5’s also appear to find SEP Question 2 more difficult to improve compared to placebo than 
SEP Question 3. Compared with the alprostadil results therefore it is assumed that the 
difference of MED2005 minus placebo for IIEF-EF is 3.2, for SEP Question 2 is 11.5 and for 
SEP Question 3 is 12. 
Estimates of standard deviations are based on FM53 and published results from other ED 
treatments and are assumed to be 5.6, 33 and 33 for IIEF-EF, SEP Question 2 and Question 
3, respectively [33, 34]. The differences between MED2005 and placebo for each endpoint are 
assumed to follow a multivariate normal distribution with the following correlation matrix, based 
on observed data from study FM53. 
IIEF-EF 
SEP Question 2 
SEP Question 3 
IIEF-EF 
1 
0.5 
0.5 
SEP Question 2 
0.5 
1 
0.6 
SEP Question 3 
0.5 
0.6 
1 
 
For the open-label extension phase it is planned to recruit a total of 450 male subjects in 
order to meet ICH requirements. 
 
15. 
DATA MANAGEMENT 
The data management process is described below and subject to change after finalisation of 
the study roles and responsibilities which will be described in detail in the Data Handling Plan 
(DHP).  
The CRO’s Data Management department will be responsible for developing and maintaining 
the DHP; setting-up and validating the clinical study database; programming validation checks; 
entering data into the clinical study database; reviewing data for accuracy, completeness and 
consistency between the eCRFs and the database; and verifying adherence to the clinical 
pharmacology study protocol and the DHP. The study database will be built using appropriate 
software based on the eCRF design. Data entry will be performed using a double independent 
data entry method with second pass verification. 
Clinical laboratory safety data will be loaded into the database as an electronic data transfer 
file according to the validated transfer specification document. Clinical data queries will be 

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generated and resolved according to the DHP. Clinical data queries will be resolved with the 
assistance of CRO and site clinical staff.  
The study will involve two database locks. For the data up to and including Visit 6, after all 
clinical data queries are resolved, the final error rate is confirmed and QC checks are 
considered acceptable, the database will be locked. The same process will apply at the end of 
the open-label extension phase. Standard SAS® datasets will be generated from the final study 
database ready for the analyses. A complete audit trail of all corrections will be available for 
inspection.  
AEs, diagnoses from Medical History and procedures from Surgical History will be classified 
according to the current version of MedDRA (Version 20.1 or higher). Previous and 
Concomitant Medications will be coded using the current version of the WHODrug dictionary 
(Version 1 March 2017 or higher). SAEs in the clinical database will be reconciled with the 
safety database. 
15.1 
Case Report Forms 
eCRFs, paper diaries (for the collection of AEs and concomitant medications) and ePRO 
devices will be used to record the data in the study. 
The Study Monitor will check data at the monitoring visits to the study sites. The PI will ensure 
that the data in the eCRFs are accurate, complete and legible.  
Any missing, impossible (inconsistent with human life) or inconsistent recordings in the eCRFs 
will be referred back to the PI and documented for each individual subject before clean file 
status is declared. 
16. 
SPONSOR AND INVESTIGATOR RESPONSIBILITIES 
This study will be conducted in accordance with current applicable regulations, ICH, 
EU Directive 2001/20/EC and local ethical and legal requirements. 
16.1 
Sponsor Responsibilities 
16.1.1 
GCP Compliance 
FMD and any third party to whom aspects of the study management or monitoring have been 
delegated will undertake their roles for this study in compliance with all applicable regulations 
and ICH GCP Guidelines. 
FMD assigns the ICH compliance statement for the study to the CRO and ensures that the 
CRO complies with ICH GCP through a program of oversight activities including, but not limited 
to, review of project meeting minutes, attending initiation visits, and review of monitoring 
reports, etc. 
Visits to the sites will be conducted to inspect study data, subject medical records and eCRFs 
in accordance with current GCP and the respective local and national government regulations 
and guidelines. Records and data may additionally be reviewed by auditors or by Regulatory 
Authorities. 
16.1.2 
Regulatory Approval 
FMD will ensure that local Regulatory Authority requirements are met before the start of the 
study. FMD (or a nominated delegate) will be responsible for the preparation, submission and 

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confirmation of receipt of any Regulatory Authority approvals required prior to study 
commencement. 
16.1.3 
Indemnity/liability and Insurance 
FMD will adhere to the recommendations of the Association of British Pharmaceutical Industry 
(ABPI) Guidelines. A copy of the indemnity document will be supplied to the CRO before study 
initiation.  
FMD will ensure that suitable insurance cover is in place prior to the start of the study. An 
insurance certificate will be supplied to the sites. 
16.1.4 
Protocol Management 
All protocols and amendments will be prepared by FMD and/or the CRO. If it becomes 
necessary to issue a protocol amendment during the course of the study, FMD will notify the 
CRO and collect documented Investigator Agreements to the amendment. 
16.1.5 
End of Study Notification 
FMD (or a nominated delegate) will submit an end of study notification to the Competent 
Regulatory Authority of the Member State within 90 days of the end of the study, in accordance 
with EU Directive 2001/20/EC and to the local Regulatory Authority according to applicable 
regulatory requirements. FMD will forward copies of the end of study notification documents to 
the CRO. The CRO or their delegate will be responsible for submitting these to the relevant 
EC within 90 days of the end of the study. 
16.1.6 
Submission of Summary of Clinical Trial Report to Competent Regulatory 
Authorities of Member States Concerned and ECs 
FMD will provide a summary of the clinical trial report within 1 year of the end of the study to 
the Competent Regulatory Authority of the Member States concerned, as required by the 
regulatory requirement and to comply with the community guideline on GCP. FMD will provide 
the PI with a copy of the summary report to forward to the relevant EC. 
16.2 
Investigator Responsibilities  
16.2.1 
GCP Compliance 
The PI will have been assigned by FMD to perform the study in accordance with ICH GCP 
Guidelines, EU Directive 2001/20/EC and the applicable regulatory requirements and local 
regulatory requirements.  
It is the PI’s responsibility to ensure that adequate time and appropriate resources are available 
at the individual study sites prior to commitment to participate in this study. The PI should also 
be able to estimate or demonstrate a potential for recruiting the required number of suitable 
subjects within the agreed recruitment period. 
The PI will maintain a list of appropriately Qualified Persons (QPs) to whom the PI has 
delegated significant study-related tasks. Up-to-date copies of the curriculum vitaes for the PI, 
Co-Investigator(s) and essential study staff will be provided to FMD (or their delegate) before 
starting the study. 

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Agreement with the final clinical study report (CSR) will be documented by a dated signature 
of the PI, in compliance with Directive 75/318/EC, Directive 2001/83/EC and ICH E3 and local 
regulatory requirements. 
16.2.2 
Protocol Adherence and Investigator Agreement 
The PI must adhere to the protocol as detailed in this document. The PI will be responsible for 
enrolling only those subjects who have met protocol eligibility criteria. The PI will be required 
to sign an Investigator Agreement to confirm acceptance and willingness for themselves and 
the Co-Investigator(s) to comply with the study protocol. 
16.2.3 
Documentation and Retention of Records 
After completion of the study, all data and documents relating to the study will be kept in a 
secure and orderly manner by the CRO or their delegate in a secure file in an electronic or 
paper TMF. The data will be available for inspection by FMD or their representatives. Unless 
other union law requires archiving for a longer period, the Sponsor and the CRO shall 
archive the content of the TMF for at least 25 years after the end of the study. However, 
the medical files of subjects shall be archived in accordance with national law. The CRO 
or their delegate must contact FMD before destroying any study-related documentation and it 
is the responsibility of FMD to inform the investigative sites of when these documents can 
be destroyed.  
16.3 
Ethical Considerations 
This protocol complies with the principles of the World Medical Assembly (Helsinki 1964) and 
subsequent amendments. 
16.3.1 
Informed Consent 
It is the responsibility of the PI to obtain written informed consent from all subjects and their 
female partners to enter the study and also to obtain written informed consent from all subjects 
and their female partners to continue into the open-label extension phase. All consent 
documentation must be in accordance with applicable regulations and GCP. Each subject and 
his partner is required to sign the subject and partner ICF after they have both read the written 
subject information and received an explanation of what the study involves. This can include, 
but is not limited to: the objectives, potential benefits and risks, inconveniences and the 
subject’s/partner’s rights and responsibilities. Signed consent forms must remain on file and 
must be available for verification by Study Monitors at any time. A signed original copy of the 
informed consent documentation (ICF or Subject Information and ICF, as applicable) must be 
given to the subject and his partner or the subject’s/partner’s legally authorised representative. 
The CRO will provide the Sponsor with a copy of the EC approved consent forms, and a copy 
of the EC written approval, prior to the start of the study. Additionally, if the EC required 
modification of the sample Subject Information and ICF documents provided by the Sponsor, 
the documentation supporting this requirement must be provided to the Sponsor. 
16.3.2 
Ethics Committee Approval  
It is the responsibility of the CRO to submit this protocol, the informed consent documents 
(approved by FMD), relevant supporting information and all types of subject recruitment 
information to the relevant EC for review, and all must be approved prior to the start of subject 
screening. Advertisements must be approved by the EC prior to their use at the study site, if 
applicable. Prior to implementing changes in the study, FMD and the ECs must also approve 
any substantial amendments to the protocol and corresponding updates to the informed 

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consent documents. For non-substantial protocol amendments (that do not require EC 
approval) and subsequent updates of the informed consent documents, all changes will be 
done in agreement with FMD and the study sites. 
The CRO is responsible for keeping the relevant EC apprised of the progress of the study and 
of any changes made to the protocol. FMD (or a nominated delegate) will keep the ECs 
informed of any serious and significant AEs.  
16.4 
Confidentiality 
Data collected during this study may be used to support the development, registration or 
marketing of a medicinal product. FMD will control all data collected during the study, and will 
abide by the General Data Protection Regulation (GDPR) (EU) 2016/679 concerning the 
processing and use of subjects’ personal data. For the purpose of GDPR, FMD will be the data 
controller. 
After subjects have consented to take part in the study, their medical records and the data 
collected during the study will be reviewed by FMD and/or its representatives. These records 
and data may, in addition, be reviewed by the following: independent auditors who validate the 
data on behalf of FMD, national or local Regulatory Authorities, and the ECs which gave 
approval for this study to proceed. 
Subjects will be known by a unique subject number. The results of this study containing the 
unique subject number and relevant medical information including ethnicity may be recorded 
and transferred to and used in other countries throughout the world, which may not afford the 
same level of protection that applies within the EU and countries participating this study. The 
purpose of any such transfer would be to support regulatory submissions made by FMD in 
such countries. 
16.5 
Publication Policy 
If the Sponsor, CRO and CI agree that it is desirable to publish the results of this study; all 
parties will liaise in good faith to publish the results. The CRO/CI agree to obtain the Sponsor’s 
prior written approval of such publications. 
17. 
REFERENCES LIST 
1. 
Wessells H, Joyce GF, Wise M, Wilt TJ. Erectile dysfunction. J Urol. 177(5):1675–81. 
2. 
Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and 
psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 
1994;151(1):54–61. 
3. 
Corona G, Lee, DM, Forti G, et al. Age-related changes in general and sexual health in 
middle-aged and older men: results from the European Male Ageing Study (EMAS). 
J Sexual Med. 2010;7(4 Pt 1):1362–80. 
4. 
Johannes CB, Araujo AB, Feldman HA, et al. Incidence of erectile dysfunction in men 40 
to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol. 
2000;163(2):460–3. 
5. 
Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction 
between 1995 and 2025 and some possible policy consequences. BJU Int. 
1999;84(1):50–6. (1999). 
6. 
NIH Consensus Conference. Impotence. JAMA. 1993;270(1):83–90. 

Futura Medical Developments Ltd              CONFIDENTIAL                       Page 71 of 80 
 
Protocol Reference: FM57                                             Version 7.0 dated 27 July 2018 
 
7. 
Miller TA. Diagnostic evaluation of erectile dysfunction. Am Fam Physician. 
2000;61(1):95–104. 
8. 
Schwarz ER, Rodriguez J. Sex and the heart. Int J Impot Res. 2005;17(Suppl 1):S4–6. 
9. 
Esposito K, Giugliano F, Di Palo C, et al. Effect of lifestyle changes on erectile 
dysfunction in obese men: a randomized controlled trial. JAMA. 2004;291(24):2978–84. 
10. 
Fazio L, Brock G. Erectile dysfunction: Management update. CMAJ. 2004;170(9):1429–
37. 
11. 
Richter S, Vardi Y, Ringel A, et al. Intracavernous injections: still the gold standard for 
treatment of erectile dysfunction. Int J Impot Res. 2001;13(3):172–5. 
12. 
Vardi Y, Sprecher E, Gruenwald I. Logistic regression and survival analysis of 450 
impotent patients treated with injection therapy: long-term dropout parameters. J Urol. 
2000;163(2):467–70. 
13. 
Kim DE, McVary TK. Topical prostaglandin-E1 for the treatment of erectile dysfunction. 
J Urol. 1995;153(6):1828–30. 
14. 
Hanchanale V, Eardley I. Alprostadil for the treatment of impotence. Expert Opin 
Pharmacother. 2014;15(3):421–8. 
15. 
Vitaros 3 mg/g Cream Summary of Product Characteristics (SPC). Accessed on 21 
February 2017. https://www.medicines.org.uk/emc/medicine/28866  
16. 
de Mey C. Opportunities for the treatment of erectile dysfunction by modulation of the 
NO axis--alternatives to sildenafil citrate. Curr Med Res Opin. 1998;14(4):187–202. 
17. 
Claes H, Baert L. Transcutaneous nitroglycerin therapy in the treatment of impotence. 
Urol Int. 1989;44(5):309–12. 
18. 
Gomaa A, Shalaby M, Osman M, et al. Topical treatment of erectile dysfunction: 
randomised double blind placebo controlled trial of cream containing aminophylline, 
isosorbide dinitrate, and co-dergocrine mesylate. BMJ. 1996;312(7045):1512–5. 
19. 
Rectogesic 4 mg/g Rectal Ointment SPC. Accessed on 21 February 2017. 
https://www.medicines.org.uk/emc/medicine/16174  
20. 
Percutol 
Ointment 
SPC. 
Accessed 
on 
21 
February 
2017. 
https://www.medicines.org.uk/emc/medicine/28295  
21. 
Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): a 
multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49(6):822–
30. 
22. 
Rosen RC, Cappelleri JC, Gendrano N 3rd. The International Index of Erectile Function 
(IIEF): a state-of-the-science review. Int J Impot Res. 2002;14(4):226–44. 
23. 
Cappelleri JC, Rosen RC, Smith MD, et al. Diagnostic evaluation of the erectile function 
domain of the International Index of Erectile Function. Urology. 1999;54(2):346–51. 
24. 
Cappelleri JC, Althof SE, Siegel RL, et al. Development and validation of the Self-Esteem 
And Relationship (SEAR) questionnaire in erectile dysfunction. Int J Impot Res. 
2004;16(1):30–8. 
25. 
Wischmann T, Schilling K, Toth B, et al. Sexuality, Self-Esteem and Partnership Quality 
in Infertile Women and Men. Geburtshilfe Frauenheilkd. 2014;74(8):759–63. 
26. 
Giuliano F, Sanchez-Ramos A, Löchner-Ernst D, et al. Efficacy and safety of tadalafil in 
men 
with 
erectile 
dysfunction 
following 
spinal 
cord 
injury. 
Arch 
Neurol. 
2007;64(11):1184–92. 

Futura Medical Developments Ltd              CONFIDENTIAL                       Page 72 of 80 
 
Protocol Reference: FM57                                             Version 7.0 dated 27 July 2018 
 
27. 
Park SY, Choi GS, Park JS, et al. Efficacy and safety of udenafil for the treatment of 
erectile dysfunction after total mesorectal excision of rectal cancer: a randomized, 
double-blind, placebo-controlled trial. Surgery. 2015;157(1):64–71. 
28. 
Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. 
Am J Obstet Gynecol. 2003;189(1):98–101. 
29. 
Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of 
changes in chronic pain intensity measured on an 11-point numerical pain rating scale. 
Pain. 2001;94(2):149–58. 
30. 
Douglas S, Lutz A, McVary KT, et al. Validation of the patient global impression of 
improvement for penile prosthesis. Ochsner J. 2016;16(4):492–5.  
31. 
Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the 
erectile function domain of the International Index of Erectile Function scale. Eur Urol. 
2011;60(5):1010–6. 
32. 
Araujo AB, Allen KR, Ni X, Rosen RC. Minimal clinically important differences in the 
vaginal insertion and successful intercourse items of the sexual encounter profile. J Sex 
Med. 2012;9(1):169–79. 
33. 
Australian Government Department of Health, Therapeutic Goods Administration. 
AusPAR Attachment 1. Extract from the Clinical Evaluation Report for alprostadil. 2015. 
Accessed 
on 
20 January 2018. 
https://www.tga.gov.au/sites/default/files/auspar-
alprostadil-160609-cer.pdf. 
34. 
European Medicines Agency. Committee for Medicinal Products for Human Use 
assessment 
report: 
avanafil. 
2013. 
Accessed 
on 
20 January 2018. 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Public_assessment_report/human/002581/WC500145207.pdf 
 
 

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18. 
APPENDIX 1 
18.1 
IIEF Questionnaire 
 
 
 

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18.2 
SEP Questionnaire  
Male Version 
1. 
Sexual Encounter Profile Diary question number 1: 
‘Were you able to achieve at least some erection (some enlargement of the penis)?’ 
2. 
Sexual Encounter Profile Diary question number 2: 
‘Were you able insert your penis into your partner's vagina?’ 
3. 
Sexual Encounter Profile Diary question number 3: 
‘Did your erection last long enough for you to have successful intercourse?’ 
4. 
Sexual Encounter Profile Diary question number 4: 
‘Were you satisfied with the hardness of your erection?’ 
5. 
Sexual Encounter Profile Diary question number 5: 
 ‘Were you satisfied overall with this sexual experience?’ 
Female Version 
1. 
Sexual Encounter Profile Diary question number 1: 
‘Was your partner able to achieve at least some erection (some enlargement of the penis)?’ 
2. 
Sexual Encounter Profile Diary question number 2: 
‘Was your partner able to insert his penis into your vagina?’ 
3. 
Sexual Encounter Profile Diary question number 3: 
‘Did your partner’s erection last long enough for you to have successful intercourse?’ 
4. 
Sexual Encounter Profile Diary question number 4: 
‘Were you satisfied with the hardness of your partner’s erection?’ 
5. 
Sexual Encounter Profile Diary question number 5: 
‘Were you satisfied overall with this sexual experience?’ 

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18.3 
SEAR Questionnaire 
Male and Female Version 
 
 

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18.4 
GAQ 
Male Version 
1. 
GAQ question number 1:  
‘Has the treatment you have been taking improved your erectile function?’ 
2. 
GAQ question number 2:  
‘If yes, has the treatment improved your ability to engage in sexual activity?’ 
Female Version 
1. 
GAQ question number 1:  
‘Has the treatment you have been taking improved your partner’s erectile function?’ 
2. 
GAQ question number 2:  
‘If yes, has the treatment improved his ability to engage in sexual activity?’ 

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18.5 
PGI Scales 
PGI-S (Severity) Scale 
Please choose the response below that best describes the severity of your erectile dysfunction 
over the past 4 weeks. 
1. 
None. 
2. 
Mild. 
3. 
Moderate. 
4. 
Severe. 
5. 
Very severe. 
PGI-C (Change) Scale 
Please choose the response below that best describes the overall change in your erectile 
dysfunction since you started using the study treatment. 
1. 
Very much better. 
2. 
Moderately better. 
3. 
A little better. 
4. 
No change. 
5. 
A little worse. 
6. 
Moderately worse. 
7. 
Very much worse. 

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18.6 
Onset and Duration of Action (Erection) and Erection Hardness 
Questions 
Male and Female Version 
1. After application of the gel, when did you (and your partner) begin to notice your erection 
starting? 
Please note: subjective measures of time will be used for all the following questions: 
 
Almost immediately. 
 
Under 5 minutes. 
 
Between 5 and 10 minutes. 
 
Between 10 and 20 minutes. 
 
Between 20 and 30 minutes. 
 
Between 30 minutes and 1 hour. 
 
Over 1 hour. 
 
Not at all. 
2. After application of the gel, when were you (and your partner) able to have penetrative 
sex? 
 
Almost immediately. 
 
Under 5 minutes. 
 
Between 5 and 10 minutes. 
 
Between 10 and 20 minutes. 
 
Between 20 and 30 minutes. 
 
Between 30 minutes and 1 hour. 
 
Over 1 hour. 
 
Not at all. 
3. From the time you began to notice your (your partner’s) erection starting, how long did it 
last (estimated minutes)? 
 
Under 5 minutes. 
 
Between 5 and 10 minutes. 
 
Between 10 and 20 minutes. 
 
Between 20 and 30 minutes. 
 
Between 30 minutes and 1 hour. 
 
Over 1 hour. 
 
Not at all. 
4. How would you rate the hardness of your (your partner’s) erection during your sexual 
encounter? 
0 
No enlargement 
1 
Penis was larger, but not hard 
2 
Penis was hard, but not hard enough for penetration 
3 
Penis was hard enough for penetration, but not completely hard 
4 
Penis was completely hard and fully rigid 

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18.7 
 Questions on Usage and Application 
1. 
Who applied the gel most of the time? You/Your partner 
2. 
Did you/your partner find the tube easy to use? Yes/No 
3. 
Did you/your partner find the gel easy to apply? Yes/No 
4. 
Would you have preferred to use a different applicator such as a pad? Yes/No 
5. 
Did you incorporate the application of the gel as part of your foreplay? Yes/No 
6. 
Did 
you 
like 
using 
the 
gel? 
Liked 
a 
lot/Mostly 
liked/Neither 
liked 
or 
disliked/Disliked/Disliked a lot.