Tioga Research, Inc. — Department of Health and Human Services SBIR Phase I: NIDA

Description

Abstract In the proposed project Tioga Research in cooperation with DMK Pharmaceuticals aims to firmly establish the feasibility of Trikamed a transdermal patch for the delivery of the novel mixed opioid receptor agonist DPI as an alternative to current options for the relief of moderate to severe chronic pain Tioga Research will leverage its huge database of molecular penetration enhancer MPE performance and draw from its vast experience with transdermal patch innovations to generate prototype DPI transdermal patches Immediate stability and DPI skin permeation will be measured and prototype patches will then be optimized for stability drug delivery and adhesion The project will conclude with an in vivo study in G ttingen mini pigs to assess systemic delivery pharmacokinetics and skin irritation at the patch application site Abuse of and addiction to opioids such as heroin morphine and prescription pain killers is a massive problem affecting health and social andamp economic welfare worldwide Despite advances in the management of chronic pain no non opioid drug is effective enough to combat severe pain Most patients with chronic pain are still prescribed opioid analgesics despite doctorsandapos increasing hesitance due to concerns of misuse abuse or diversion Prescription opioid medicines such as morphine fentanyl and hydrocodone produce their therapeutic benefit as well as their addictive and adverse effects by selectively binding to and activating mu opioid receptors In con trast DPI acts like the body s natural opioid peptides enkephalin endorphin and dynorphin in that it is an agonist at all principal opioid receptors mu delta and kappa DPI is a new chemical entity designed to have an improved safety profile and broader therapeutic index than current opiates No other drug like DPI mu kappa and delta mixed agonist is currently on the market or in development DPI has demonstrated strong antinociceptive activity in non clinical models of acute pain In preclinical mod els compared to mu analgesics DPI showed reduced potential for respiratory depression nausea consti pation and urticaria in rodents and substantially reduced abuse potential in non human primates In a study conducted by NIH with rhesus monkeys DPI was found to be fold less potent in reinforcing effects than alfentanil and less active than alfentanil in terms of these reinforcing effects In a randomized single center double blind placebo controlled dose escalating Phase study in human subjects intravenous DPI was well tolerated with no findings of clinical concern at any dose tested These data indicate that DPI will have analgesic benefits at least comparable to that of morphine and fen tanyl but with a far better tolerability profile it offers a larger safety margin for respiratory depression and signif icantly reduced abuse potential The transdermal patch format for DPI Trikamed will optimize the dosing profile boost patient compliance and discourage abuse attempts Trikamed could thus represent a step out alternative to current opioid analgesics with the potential to replace a large proportion of the opioid market Narrative The abuse of and addiction to opioids is a serious global problem affecting health and social and economic welfare worldwide Trikamed a transdermal patch for the delivery of the novel mixed opioid receptor agonist DPI presents an alternative for the relief of moderate to severe chronic pain Unlike most opioid analge sics that produce their therapeutic benefit as well as their addictive and adverse effects by selectively binding to and activating only the mu opioid receptors DPI mimics the body s natural opioid peptides as an ago nist at all opioid receptors mu delta and kappa As a transdermal patch Trikamed has the potential to optimize the dosing profile maximize patient compliance and further discourage abuse attempts