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. Treatment requires the application of a small quantity of gel (approx 300 mg), containing a fixed dose of GTN, to the glans of the penis. Pharmacokinetic studies in healthy volunteers indicate rapid absorption of the drug and low systemic exposure, reducing the risk of adverse events (such as headache) commonly associated with GTN therapy.
The purpose of this study is to demonstrate similar or lower bioavailability of GTN from MED2005 (test IMP) with that from Nitrostat (reference IMP).
The study will be conducted in two parts (Part 1 and 2). Part 1 will be conducted in 30 subjects and Part 2 will be conducted in 10 subjects. Part 1 will compose of a pre-study screen, followed by six treatment periods and a post-study follow-up.
Part 2 will compose of a pre-study screen, followed by two treatment periods and a post-study follow-up. Subjects can only participate in either Part 1 or 2 of the study (not both).
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Erectile Dysfunction | Drug: MED2005 Drug: Nitrostat 0.6Mg Sublingual Tablet Drug: Nitro Pohl | Phase 1 |
GTN is a well-established vasodilatory therapeutic agent with a long, documented history of use and comprehensive safety profile. In Europe, licensed indications for GTN include the treatment and prophylaxis of angina pectoris and the relief of pain associated with chronic anal fissure. Other indications for prescription only parenteral products include use during cardiac surgery and for emergency reduction of blood pressure.
GTN's vasodilatory action is thought to result from the release of nitric oxide (NO) in vascular smooth muscle. NO stimulates guanylate cyclase, the enzyme responsible for production of cGMP, whose action is to lower intracellular calcium resulting in smooth muscle relaxation and vasodilation.
In the case of erectile dysfunction, GTN works locally by penetrating the glans/penile skin and directly targeting penile blood vessels. Nitrates appear to have a direct, local effect on penile haemodynamics. The most likely mechanism for the erectile effect of nitrates involves nitrate induced dilation of the cavernous and helicine arteries, thereby increasing blood flow to the lacunar spaces, coupled with nitrate-induced relaxation of trabecular smooth muscle.
Nitroglycerin (Nitrostat) is indicated for the acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease.
The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload). Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.
Nitroglycerin forms free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 40 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Diagnostic |
Official Title: | A Single Centre, Open-label, Randomised, Single Dose, Six Period, Reference Replicate, Crossover Study to Evaluate the Bioavailability of MED2005 |
Actual Study Start Date : | November 15, 2017 |
Actual Primary Completion Date : | April 16, 2018 |
Actual Study Completion Date : | April 16, 2018 |
Arm | Intervention/treatment |
---|---|
Experimental: MED2005 (0.6 mg)
MED2005 (0.2% GTN) gel to be used topically in Part 1 of the study
|
Drug: MED2005
(Day -1 to Day 1): Subjects will undergo six treatment periods, each separated by at least a two day washout. Each treatment period will be approximately 1 day in duration from the afternoon of Day -1 to the afternoon of Day 1 at 6 hours (h) post-dose. In each of the treatment periods, the subject will receive one of the six administrations over 6 treatment periods (1/period) and will return approximately two days later for the next treatment period.
Other Name: glyceryl trinitrate
Drug: Nitrostat 0.6Mg Sublingual Tablet Active comparator to be used for Part 1 of the study. Nitrostat will be dosed in two treatment periods and 3 x 0.6 mg tablets will be required to make up the 1.8 mg dose.
Other Name: Nitroglycerin 0.6 mg
|
Experimental: MED2005 (1.2 mg)
MED2005 (0.4% GTN) gel to be used topically in Part 1 of the study
|
Drug: MED2005
(Day -1 to Day 1): Subjects will undergo six treatment periods, each separated by at least a two day washout. Each treatment period will be approximately 1 day in duration from the afternoon of Day -1 to the afternoon of Day 1 at 6 hours (h) post-dose. In each of the treatment periods, the subject will receive one of the six administrations over 6 treatment periods (1/period) and will return approximately two days later for the next treatment period.
Other Name: glyceryl trinitrate
Drug: Nitrostat 0.6Mg Sublingual Tablet Active comparator to be used for Part 1 of the study. Nitrostat will be dosed in two treatment periods and 3 x 0.6 mg tablets will be required to make up the 1.8 mg dose.
Other Name: Nitroglycerin 0.6 mg
|
Experimental: MED2005 (1.8 mg)
MED2005 (0.6% GTN) gel to be used topically in Part 1 of the study
|
Drug: MED2005
(Day -1 to Day 1): Subjects will undergo six treatment periods, each separated by at least a two day washout. Each treatment period will be approximately 1 day in duration from the afternoon of Day -1 to the afternoon of Day 1 at 6 hours (h) post-dose. In each of the treatment periods, the subject will receive one of the six administrations over 6 treatment periods (1/period) and will return approximately two days later for the next treatment period.
Other Name: glyceryl trinitrate
Drug: Nitrostat 0.6Mg Sublingual Tablet Active comparator to be used for Part 1 of the study. Nitrostat will be dosed in two treatment periods and 3 x 0.6 mg tablets will be required to make up the 1.8 mg dose.
Other Name: Nitroglycerin 0.6 mg
|
Active Comparator: Nitrostat (1.8 mg) - Treatment Period 1
3 x 0.6 mg tablets will be required to make up the 1.8 mg dose to be used orally in Part 1 of the study but to be dosed in two treatment periods
|
Drug: MED2005
(Day -1 to Day 1): Subjects will undergo six treatment periods, each separated by at least a two day washout. Each treatment period will be approximately 1 day in duration from the afternoon of Day -1 to the afternoon of Day 1 at 6 hours (h) post-dose. In each of the treatment periods, the subject will receive one of the six administrations over 6 treatment periods (1/period) and will return approximately two days later for the next treatment period.
Other Name: glyceryl trinitrate
Drug: Nitrostat 0.6Mg Sublingual Tablet Active comparator to be used for Part 1 of the study. Nitrostat will be dosed in two treatment periods and 3 x 0.6 mg tablets will be required to make up the 1.8 mg dose.
Other Name: Nitroglycerin 0.6 mg
|
Active Comparator: Nitrostat (1.8 mg) - Treatment Period 2
3 x 0.6 mg tablets will be required to make up the 1.8 mg dose to be used orally in Part 1 of the study but to be dosed in two treatment periods
|
Drug: MED2005
(Day -1 to Day 1): Subjects will undergo six treatment periods, each separated by at least a two day washout. Each treatment period will be approximately 1 day in duration from the afternoon of Day -1 to the afternoon of Day 1 at 6 hours (h) post-dose. In each of the treatment periods, the subject will receive one of the six administrations over 6 treatment periods (1/period) and will return approximately two days later for the next treatment period.
Other Name: glyceryl trinitrate
Drug: Nitrostat 0.6Mg Sublingual Tablet Active comparator to be used for Part 1 of the study. Nitrostat will be dosed in two treatment periods and 3 x 0.6 mg tablets will be required to make up the 1.8 mg dose.
Other Name: Nitroglycerin 0.6 mg
|
Experimental: MED2005 (2.4 mg)- Part 1
MED2005 (0.8% GTN) gel to be used topically in Part 1 of the study
|
Drug: MED2005
(Day -1 to Day 1): Subjects will undergo six treatment periods, each separated by at least a two day washout. Each treatment period will be approximately 1 day in duration from the afternoon of Day -1 to the afternoon of Day 1 at 6 hours (h) post-dose. In each of the treatment periods, the subject will receive one of the six administrations over 6 treatment periods (1/period) and will return approximately two days later for the next treatment period.
Other Name: glyceryl trinitrate
Drug: Nitrostat 0.6Mg Sublingual Tablet Active comparator to be used for Part 1 of the study. Nitrostat will be dosed in two treatment periods and 3 x 0.6 mg tablets will be required to make up the 1.8 mg dose.
Other Name: Nitroglycerin 0.6 mg
|
Active Comparator: Intravenous (I.V.) dose of GTN (0.3 mg)
GTN solution for infusion (1 mg/ml) to be used intravenously in Part 2 of the study
|
Drug: Nitro Pohl
to be dosed intravenously in Part 2 of the study
Other Name: Nitroglycerin
|
Experimental: MED2005 (2.4 mg)- Part 2
MED2005 (0.8% GTN) gel to be used topically in Part 2 of the study
|
Drug: Nitro Pohl
to be dosed intravenously in Part 2 of the study
Other Name: Nitroglycerin
|
Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
Sexes Eligible for Study: | Male |
Gender Based Eligibility: | Yes |
Gender Eligibility Description: | Yes |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Subjects (unless anatomically sterile (documented evidence) or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) and sexual partners must use 2 effective contraception methods during the trial and for 3 months after the last dose, for example:
Exclusion Criteria:
United Kingdom | |
Simbec Research Limited | |
Merthyr Tydfil, Wales, United Kingdom, CF48 4DR |
Principal Investigator: | Samuel Israel, Israel | Simbec Research |
Tracking Information | |||||||
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First Submitted Date ICMJE | January 24, 2018 | ||||||
First Posted Date ICMJE | July 5, 2019 | ||||||
Last Update Posted Date | July 5, 2019 | ||||||
Actual Study Start Date ICMJE | November 15, 2017 | ||||||
Actual Primary Completion Date | April 16, 2018 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | No Changes Posted | ||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Evaluating MED2005 & Nitrostat Bioavailability | ||||||
Official Title ICMJE | A Single Centre, Open-label, Randomised, Single Dose, Six Period, Reference Replicate, Crossover Study to Evaluate the Bioavailability of MED2005 | ||||||
Brief Summary |
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. Treatment requires the application of a small quantity of gel (approx 300 mg), containing a fixed dose of GTN, to the glans of the penis. Pharmacokinetic studies in healthy volunteers indicate rapid absorption of the drug and low systemic exposure, reducing the risk of adverse events (such as headache) commonly associated with GTN therapy. The purpose of this study is to demonstrate similar or lower bioavailability of GTN from MED2005 (test IMP) with that from Nitrostat (reference IMP). The study will be conducted in two parts (Part 1 and 2). Part 1 will be conducted in 30 subjects and Part 2 will be conducted in 10 subjects. Part 1 will compose of a pre-study screen, followed by six treatment periods and a post-study follow-up. Part 2 will compose of a pre-study screen, followed by two treatment periods and a post-study follow-up. Subjects can only participate in either Part 1 or 2 of the study (not both). |
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Detailed Description |
GTN is a well-established vasodilatory therapeutic agent with a long, documented history of use and comprehensive safety profile. In Europe, licensed indications for GTN include the treatment and prophylaxis of angina pectoris and the relief of pain associated with chronic anal fissure. Other indications for prescription only parenteral products include use during cardiac surgery and for emergency reduction of blood pressure. GTN's vasodilatory action is thought to result from the release of nitric oxide (NO) in vascular smooth muscle. NO stimulates guanylate cyclase, the enzyme responsible for production of cGMP, whose action is to lower intracellular calcium resulting in smooth muscle relaxation and vasodilation. In the case of erectile dysfunction, GTN works locally by penetrating the glans/penile skin and directly targeting penile blood vessels. Nitrates appear to have a direct, local effect on penile haemodynamics. The most likely mechanism for the erectile effect of nitrates involves nitrate induced dilation of the cavernous and helicine arteries, thereby increasing blood flow to the lacunar spaces, coupled with nitrate-induced relaxation of trabecular smooth muscle. Nitroglycerin (Nitrostat) is indicated for the acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease. The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload). Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear. Nitroglycerin forms free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Primary Purpose: Diagnostic |
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Condition ICMJE | Erectile Dysfunction | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE |
40 | ||||||
Original Actual Enrollment ICMJE | Same as current | ||||||
Actual Study Completion Date ICMJE | April 16, 2018 | ||||||
Actual Primary Completion Date | April 16, 2018 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 50 Years (Adult) | ||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United Kingdom | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04008732 | ||||||
Other Study ID Numbers ICMJE | FM58 | ||||||
Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Futura Medical Developments Ltd. | ||||||
Study Sponsor ICMJE | Futura Medical Developments Ltd. | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | Futura Medical Developments Ltd. | ||||||
Verification Date | July 2019 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |