NCT04008732

Evaluating MED2005 & Nitrostat Bioavailability

A Single Centre, Open-label, Randomised, Single Dose, Six Period, Reference Replicate, Crossover Study to Evaluate the Bioavailability of MED2005

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Futura Medical Developments Ltd. · Industry
• Sex: Male
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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).

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.

Conditions

• Erectile Dysfunction

Interventions

Type	Name	Description
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.
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.
DRUG	Nitro Pohl	to be dosed intravenously in Part 2 of the study

Timeline

• Start date: 2017-11-15
• Primary completion: 2018-04-16
• Completion: 2018-04-16
• First posted: 2019-07-05
• Last updated: 2019-07-05

Locations

1 site across 1 country: United Kingdom

Regulatory

• FDA-regulated drug study