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

Erectile Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03813992
• Other study ID #: FM57
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2018
• Est. completion date: January 17, 2020

Study information

• Verified date: February 2022
• Source: Futura Medical Developments Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1005
• Est. completion date: January 17, 2020
• Est. primary completion date: July 21, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Subject is a male aged between 18 and 70 years inclusive, at screening

2. Confirmed clinical diagnosis of ED for more than 3 months according to the NIH Consensus Statement ('the inability to achieve or maintain penile erection sufficient for satisfactory sexual performance at least once')

3. Subject answers 'yes' to the question regarding the presence of residual EF over the past 3 months: 'At home over the past 3 months, have you experienced at least some growth of your penis in response to: (1) mechanical stimulation by yourself or your partner, or (2) visual stimulation?'

4. Subject has been involved in a continuous heterosexual relationship for at least 6 months prior to screening

5. Documented written informed consent from both subject and his female partner

6. If the male subject's female partner is of childbearing potential from the time of first sexual intercourse attempt during the screening period until the last administration of study treatment, then the couple must have been using a medically acceptable form of contraception for at least 3 months prior to entering the study, and agree to continue such use for at least 1 month after the last study drug administration. Subjects who are or wish to become pregnant will not be included in the study.

7. Subject and his female partner are capable of understanding and complying with the requirements of the protocol and must have signed the ICF prior to participation in any study related procedures

8. Low IIEF-EF scores (= 25) during the screening period

To continue in the open-label extension phase of the study, subjects must meet the following inclusion criteria at the follow-up visit of the double-blind phase (Visit 6):

1. Subject and his female partner complete the double-blind phase

2. Subject and his female partner were compliant to study procedures during the double blind phase

3. Documented written informed consent from both subject and his female partner

4. If the male subject's female partner is of childbearing potential from the time of first sexual intercourse attempt during the screening period until the last administration of study treatment, then the couple must have been using a medically acceptable form of contraception for at least 3 months prior to entering the study, and agree to continue such use for at least 1 month after the last study drug administration. Subjects who are or wish to become pregnant will not be included in the study.

Exclusion Criteria:

1. Any significant or serious cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological or psychiatric disease which, in the opinion of the PI, renders the subject unfit to take part in the study

2. Subject has any history of an unstable medical or psychiatric condition or using any medication that, in the opinion of the PI, is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study Certain concomitant medications; e.g. other vasodilators, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, beta blockers, diuretics, anti hypertensives, tricyclic anti depressants and major tranquillisers, as well as the consumption of alcohol, may potentiate the BP lowering effects of MED2005; therefore, the PI must consider this carefully and include subjects at their discretion

3. Any presence of a symptomatic, active urinary tract infection diagnosed by the PI or their delegate at screening or during the study

4. Any presence of chronic indwelling urethral catheterisation or penile anatomical abnormalities (e.g. penile fibrosis) that would significantly impair EF

5. Any history of operations for Peyronie's disease

6. Primary hypoactive sexual desire or any history of hypogonadism

7. Any history of radical prostatectomy

8. Any history of severe/uncontrolled diabetes

9. Subjects taking two or more anti hypertensives for the treatment of BP

10. Hypersensitivity to GTN or to any of the excipients, or idiosyncratic reactions to other organic nitrates

11. Concomitant treatment with sildenafil citrate, tadalafil, vardenafil and other PDE 5 inhibitors

12. Subjects taking Alpha blockers

13. Subjects receiving testosterone pellets

14. Any penile surgery except circumcision

15. Any treatment with acetyl cysteine within 6 months

16. Any treatment with dihydroergotamine within 6 months

17. Postural hypotension, hypotension or uncorrected hypovolaemia, as the use of GTN in such states could produce severe hypotension or shock

18. Increased intracranial pressure (e.g. head trauma or cerebral haemorrhage) or inadequate cerebral circulation

19. Any history of migraine or recurrent headache

20. Aortic or mitral stenosis

21. Hypertrophic obstructive cardiomyopathy

22. Constrictive pericarditis or pericardial tamponade

23. Closed-angle glaucoma

24. Subjects with nursing partners, known pregnant partners or with partners who wish to become pregnant during the course of the study

25. Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates, tricyclic antidepressants and methadone) or from the alcohol breath test at screening (for clarification, any positive result from the urine drug screen or alcohol breath tests at screening will mean the subject will be excluded from the study). In the instance that a subject is using medication which may give a positive result, exclusion will be at the PI's discretion

26. Subject has recent (last 12 months) clinical evidence of alcoholism or drug abuse.

27. Subject has a positive screen for hepatitis B, consisting of hepatitis B surface antigen (HBsAG), hepatitis C antibody, and human immunodeficiency virus (HIV)

28. Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission

29. Subjects unwilling to cease use of vacuum devices, intracavernosal injections, PDE-5s or other therapy for ED for the entire course of the study

30. Unwillingness of the subject or their partner to agree to make the required attempts at sexual intercourse during treatment period

31. Any history of unresponsiveness to PDE 5 treatment or significant side effects, excluding visual disturbances, with PDE 5s

32. Fewer than four attempts at sexual intercourse during the screening period

33. Subjects or their partners who are illiterate or are unable to understand the language in which the questionnaires are available

34. Subject has received any investigational product during the 90 days prior to dosing for this study

35. Subject or his partner cannot communicate reliably with the PI

36. Subjects with severe premature ejaculation (little or no control of ejaculation at the time of penetration)

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

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

2. Subject using any medication that, in the opinion of the PI, is likely to affect the subject's ability to complete or participate in the open-label phase of the study.

NB The concomitant medications listed as exclusion criteria for the study apply to the open-label extension phase. Certain concomitant medications; e.g. other vasodilators, calcium channel blockers, ACE inhibitors, beta blockers, diuretics, anti hypertensives, tricyclic anti depressants and major tranquillisers, as well as the consumption of alcohol, may potentiate the BP lowering effects of MED2005; therefore, the PI must consider this carefully and include subjects at their discretion

3. Any presence of a symptomatic, active urinary tract infection diagnosed by the PI or their delegate at the start of the open-label extension phase

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

Related Conditions & MeSH terms

• Erectile Dysfunction

Intervention

Drug:
• MED2005
Topical Product

Locations

Country	Name	City	State
Bulgaria	UMHAT Burgas EAD	Burgas
Bulgaria	Multiprofile Hospital for Active Treatment	Pleven
Bulgaria	University Multiprofile Hospital for Active Treatment	Plovdiv
Bulgaria	Urology Office Diagnostic-Consultative Center	Varna
Bulgaria	Medical Center Biomed	Vidin
Czechia	URAN MUDr.Jan Hiblbauer s.r.o	Hradec Králové
Czechia	ANDROGEOS, spol. s.r.o.	Praha
Czechia	Urosante s.r.o.	Praha
Georgia	LTD Gormedi	Gori
Georgia	LTD Gidmedi	Tbilisi
Georgia	LTD Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	LTDHealth House	Tbilisi
Hungary	Synexus Magyarorszag Kft	Budapest
Hungary	Civis Egeszseghaz	Debrecen
Hungary	Korona Prevent-Med Kft.	Sopron
Hungary	Aranyklinika	Szeged
Latvia	Latgales Urology Center	Daugavpils
Latvia	V. Lietuviesa Private Practice	Riga
Latvia	Vidzemes Hospital	Valmiera
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Dr Adam Sipinski	Katowice
Poland	PROVITA Specjalistyczna Praktyka Ginekologiczno-Seksuologiczna	Lublin
Poland	Indywidualna Specjalistyczna Praktyka Lekarska	Szczecin
Poland	Gabinet Lekarski Ryszard Smolinski	Wroclaw
Russian Federation	Regional Budgetary Healthcare Institution "Ivanovskaya Regional Clinical Hospital"	Ivanovo
Russian Federation	CJSC "Nasledniki"	Moscow
Russian Federation	Federal State Budgetary Institution "National Medical Research Center of Obstetrics, Gynecology and Perinatology n.a. acad. V.I. Kulakov" of the Ministry of Healthcare of the Russian Federation	Moscow
Russian Federation	FSBEI HE "Russian National Research Medical University n.a. N.I. Pirogov" of the Ministry of Healthcare of the Russian Federation, Russian Gerontological Scientific and Research Center	Moscow
Russian Federation	LLC "Bessalar Clinic"	Moscow
Russian Federation	LLC "Unimed-S"	Moscow
Russian Federation	State Budgetary Institution "Hospital for War Veterans"	Rostov-on-Don
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "North-Western State Medical University n.a. I.I. Mechnikov" of the Ministry of Healthcare of the Russian Federation	Saint Petersburg
Russian Federation	LLC "Medical center PRIME ROSE"	Saint Petersburg
Russian Federation	LLC "Sanavita"	Saint Petersburg
Russian Federation	Llc <<Mart>>	Saint Petersburg
Russian Federation	Medicosanitary Department No.70, branch of Saint-Petersburg State Unitary Institution of road passenger transport	Saint Petersburg
Russian Federation	Research Center "Eco-Safety"	Saint Petersburg
Russian Federation	Saint Petersburg State Budgetary Healthcare Institution "City Polyclinic No. 4"	Saint Petersburg
Russian Federation	Clinical Hospital n.a. S.R. Mirotvortseva of the Federal State Budgetary Educational Institution of Higher Education "Saratovskiy State Medical University n.a. V.I. Razumovskiy" of the Ministry of Healthcare of the Russian Federation	Saratov
Russian Federation	Federal State Budgetary Educational Institution of Higher Education " Voronezhskiy State Medical University n.a. N.N. Burdenko" of the Ministry of Healthcare of the Russian Federation on the clinical base of Budgetary Healthcare Institution of Voronezhsk	Voronezh
Russian Federation	SBHI of Leningradskaya region "Vsevolozhskaya Clinical Interdistrict Hospital"	Vsevolozhsk
Russian Federation	FSBEI HPE "Yaroslavskiy State Medical University" of The Ministry of Healthcare of the Russian Federation with clinical base in State Autonomous Institution of Yaroslavskaya region "Clinical Hospital No.9"	Yaroslavl
Slovakia	Urologicka ambulancia	Košice
Slovakia	Urologicka ambulancia Urobet s.r.o.	Malacky
Slovakia	Urologicka ambulancia Uroexam s.r.o.	Nitra
Slovakia	Privatna urologicka ambulancia s.r.o.	Trencín
Ukraine	Municipal Establishment "Cherkasy Regional Hospital of Cherkasy Regional Council", Urology department	Cherkasy
Ukraine	Regional Clinical Hospital, Polyclinic Department	Ivano-Frankivs'k
Ukraine	Kyiv Clinical Hospital on Railway Transport #1 of the branch "Health Center" of the public joint stock company "Ukrainian Railway", consulting and diagnostic center	Kyiv
Ukraine	State Institution "Institute of urology of the National Academy of Medical Science of Ukraine", policlinic department	Kyiv
Ukraine	State Institution "Institute of urology of the National Academy of Medical Sciences of Ukraine", Department of Sexual Pathology and Andrology	Kyiv
Ukraine	"Ambulatory of General Practice-Family Medicine",LLC, Medical Center	Odesa
Ukraine	Private Small-Scale Enterprise Medical Centre "Pulse" , Therapeutic Department	Vinnytsia
Ukraine	Municipal Institution Central City Hospital ?1 of Zhytomyr, consulting and medical department "Research center"	Zhytomyr

Sponsors (1)

Lead Sponsor	Collaborator
Futura Medical Developments Ltd.

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Georgia,  Hungary,  Latvia,  Poland,  Russian Federation,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	International Index for Erectile Function (IIEF) Questionnaire	A questionnaire containing 15 questions divided into 5 domains; erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction.	Up to Week 64 of the study
Primary	Sexual Encounter Profile (SEP) Questionnaire (Question 2)	A questionnaire consisting of 5 items assessing the sexual events a patient experiences during sexual intercourse.	Up to Week 64 of the study
Primary	Sexual Encounter Profile (SEP) Questionnaire (Question 3)	A questionnaire consisting of 5 items assessing the sexual events a patient experiences during sexual intercourse.	Up to Week 64 of the study
Secondary	Self-Esteem and Relationship (SEAR) Questionnaire	A questionnaire to support the validity and reliability for measuring sexual relationship satisfaction, satisfaction, confidence, and self-esteem in men with erectile dysfunction.	Up to Week 12 of the study.
Secondary	Global Assessment Questionnaire (GAQ)	A questionnaire that allows patients and their partners to rate (yes or no) an improvement in erectile function.	Up to Week 12 of the study.
Secondary	International Index for Erectile Function (IIEF) Questionnaire (additional domains)	A questionnaire containing 15 questions divided into 5 domains; erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction.	Up to Week 64 weeks of the study.
Secondary	Sexual Encounter Profile (SEP) Questionnaire (Questions 1, 4 & 5)	A questionnaire consisting of 5 items assessing the sexual events a patient experiences during sexual intercourse.	Up to Week 64 of the study.
Secondary	Sexual Encounter Profile (SEP) Questionnaire	A questionnaire consisting of 5 items assessing the sexual events a patient experiences during sexual intercourse.	Up to Week 64 of the study
Secondary	Patient Global Impression of Severity (PGI-S)	A one item questionnaire to rate the severity of a patient's erectile dysfunction. This is a single-state 5-point categorical scale.	Up to Week 12 of the study.
Secondary	Patient Global Impression of Change (PGI-C)	A one item questionnaire to rate a perceived change in a patient's erectile function. This is a transitional 7-point categorical scale.	Up to Week 12 of the study
Secondary	Onset and duration of action (erection) and erection hardness	A questionnaire asking both the patient and the patient's partner about the onset and duration of action of the patient's erection.	Up to Week 12 of the study
Secondary	Usage and application	A questionnaire has 5 items to assess the usage and application of the investigation product.	Up to Week 12 of the study