Evaluating MED2005 & Nitrostat Bioavailability

NCT04008732 | Completed Phase 1 FDA Drug

• 1 other identifier: FM58
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Erectile Dysfunction

Outcome Measures

Primary Outcomes (3)

• To demonstrate similar or lower bioavailability of GTN when administered as a gel via MED2005 compared to Nitrostat (which will administrated as a sublingual tablet) in terms of AUC0-t (Part 1)

  The primary objective of this human pharmacology study is to demonstrate similar or lower bioavailability of GTN

  22 days

• To demonstrate similar or lower bioavailability of GTN when administered as a gel via MED2005 compared to Nitrostat (which will administrated as a sublingual tablet) in terms of AUC0-inf (Part1)

  The primary objective of this human pharmacology study is to demonstrate similar or lower bioavailability of GTN

  22 days

• To demonstrate similar or lower bioavailability of GTN when administered as a gel via MED2005 compared to Nitrostat (which will administrated as a sublingual tablet) in terms of Cmax (part1)

  The primary objective of this human pharmacology study is to demonstrate similar or lower bioavailability of GTN

  22 days

Secondary Outcomes (5)

• The pharmacokinetics of GTN metabolite 1,2-GDN will be evaluated following the administration of MED2005 compared with Nitrostat (Part 1).

  22 days

• Adverse events (AEs) coded using Medical Dictionary for Regulatory Activities (MedDRA) version 20.0 or higher

  46 days

• GTN absorption (to quantify the amount of GTN remaining on the glans penis post application)

  10 days

• GTN absorption (to quantify a figure of 100% GTN being absorbed)

  10 days

• The pharmacokinetics of GTN metabolite1,3-GDN will be evaluated following the administration of MED2005 compared with Nitrostat (Part 1).

  22 days

Study Arms (8)

MED2005 (0.6 mg)

EXPERIMENTAL

MED2005 (0.2% GTN) gel to be used topically in Part 1 of the study

Drug: MED2005; Drug: Nitrostat 0.6Mg Sublingual Tablet

MED2005 (1.2 mg)

EXPERIMENTAL

MED2005 (0.4% GTN) gel to be used topically in Part 1 of the study

Drug: MED2005; Drug: Nitrostat 0.6Mg Sublingual Tablet

MED2005 (1.8 mg)

EXPERIMENTAL

MED2005 (0.6% GTN) gel to be used topically in Part 1 of the study

Drug: MED2005; Drug: Nitrostat 0.6Mg Sublingual Tablet

Nitrostat (1.8 mg) - Treatment Period 1

ACTIVE COMPARATOR

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; Drug: Nitrostat 0.6Mg Sublingual Tablet

Nitrostat (1.8 mg) - Treatment Period 2

ACTIVE COMPARATOR

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; Drug: Nitrostat 0.6Mg Sublingual Tablet

MED2005 (2.4 mg)- Part 1

EXPERIMENTAL

MED2005 (0.8% GTN) gel to be used topically in Part 1 of the study

Drug: MED2005; Drug: Nitrostat 0.6Mg Sublingual Tablet

Intravenous (I.V.) dose of GTN (0.3 mg)

ACTIVE COMPARATOR

GTN solution for infusion (1 mg/ml) to be used intravenously in Part 2 of the study

Drug: Nitro Pohl

MED2005 (2.4 mg)- Part 2

EXPERIMENTAL

MED2005 (0.8% GTN) gel to be used topically in Part 2 of the study

Drug: Nitro Pohl

Interventions

MED2005 DRUG

(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.

Also known as: glyceryl trinitrate

MED2005 (0.6 mg); MED2005 (1.2 mg); MED2005 (1.8 mg); MED2005 (2.4 mg)- Part 1; Nitrostat (1.8 mg) - Treatment Period 1; Nitrostat (1.8 mg) - Treatment Period 2

Nitrostat 0.6Mg Sublingual Tablet DRUG

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.

Also known as: Nitroglycerin 0.6 mg

MED2005 (0.6 mg); MED2005 (1.2 mg); MED2005 (1.8 mg); MED2005 (2.4 mg)- Part 1; Nitrostat (1.8 mg) - Treatment Period 1; Nitrostat (1.8 mg) - Treatment Period 2

Nitro Pohl DRUG

to be dosed intravenously in Part 2 of the study

Also known as: Nitroglycerin

Intravenous (I.V.) dose of GTN (0.3 mg); MED2005 (2.4 mg)- Part 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Yes
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects between 18 and 50 years of age, inclusive (at screening).
• A BMI of 18.5-30 kg/m2 (inclusive).
• No clinical significant abnormal serum biochemistry, haematology and urine examination values as defined by the Investigator.
• A negative urinary drugs of abuse screen. A positive alcohol test may be repeated on admission at the discretion of the Investigator.
• Negative HIV and Hepatitis B and C results.
• No clinically significant abnormalities in 12-lead ECG as defined by the Investigator.
• No clinically significant deviation outside the normal ranges for blood pressure and heart rate measurements as defined by the Investigator (please refer to appendix 1 for normal ranges).
• 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:
• Oral contraceptive + condom.
• Intra-uterine device (IUD) + condom.
• Diaphragm with spermicide + condom.
• Subjects must be available to complete all periods of the study and the follow-up visit.
• Subjects must satisfy the PI / designee about their fitness to participate in the study.
• Subjects must be able to read and understand the informed consent form and must provide written informed consent to participate in the study.

You may not qualify if:

• A clinically significant history of gastrointestinal disorder likely to influence IMP absorption (Part 1 only).
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 28 days (or 5 half-lives (whichever is longer) prior to the first dose of IMP, unless in the opinion of the Investigator and Sponsor's Responsible Physician the medication will not interfere with the study procedures or compose subject safety.
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
• A clinically significant history of drug or alcohol abuse within 2 years before the first dose of IMP.
• A clinically significant history of previous allergy/sensitivity to GTN, other nitrates and/or any of the excipients in either the test of reference products.
• Recent history of using PDE5 inhibitors or alkyl nitrates (e.g. poppers).
• A history of frequent tension headaches or vascular headaches or migraine.
• A history of increased intra-cranial pressure or spinal cord injury.
• A history of severe psychological disorders.
• A presence of scarring/piercings/tattoos at the site of MED2005 administration (penis) (or any other features that the Investigator considers may influence IMP absorption).
• Subjects (if uncircumcised) who are not able to retract foreskin of penis easily without any discomfort.
• Any obvious sensitivity/local tolerability issues at the site of medication application.
• Inability to communicate well with the investigator (i.e. language problems, poor mental development or impaired cerebral function).
• Participation in a New Chemical Entity or marketed drug clinical study within the previous 3 months or, five half-lives of study drug, whichever is the longer period. (NB. the three month washout period between trials is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
• Subjects who smoke (or ex-smokers) who have smoked or used nicotine-containing products (including snuff, chewing tobacco, cigars, pipes or nicotine replacement products) within four months prior to first dose.

Sponsors & Collaborators

• Futura Medical Developments Ltd.: lead

Study Sites (1)

Simbec Research Limited

Merthyr Tydfil, Wales, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Erectile Dysfunction

Interventions

Nitroglycerin; Administration, Sublingual

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals; Administration, Oral; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Samuel Israel, Israel

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2018
• First Posted: July 5, 2019
• Study Start: November 15, 2017
• Primary Completion: April 16, 2018
• Study Completion: April 16, 2018
• Last Updated: July 5, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)