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Prevention of renarcotization from synthetic opioids

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41DA050386-01
Agency Tracking Number: R41DA050386
Amount: $305,204.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIDA
Solicitation Number: DA19-020
Solicitation Year: 2019
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-30
Award End Date (Contract End Date): 2020-08-31
Small Business Information
2403 SIDNEY ST, STE 255
Pittsburgh, PA 15203-2194
United States
DUNS: 080973863
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (412) 359-4943
Business Contact
Phone: (412) 213-8788
Research Institution
PITTSBURGH, PA 15212-5862
United States

 Domestic Nonprofit Research Organization

In October 2017, the U.S. Government declared the current opioid epidemic the worst drug crisis in American
history. Synthetically derived opioids such as fentanyl and fentanyl-derivatives have been at the forefront of
this public health emergency, exhibiting the highest year-to-year contribution to overdose deaths. While the
mu opioid receptor (MOR) antagonist naloxone has proven invaluable as an opioid overdose antidote,
naloxone suffers from a very short duration of action (half-life ~ 1hr.) and has been found to be less effective
against newer, long acting opioids including fentanyl (half-life ~7-10 hrs.). This leads to a highly lethal and
increasingly prevalent phenomenon known as “renarcotization”, wherein an overdose patient revived with
naloxone can re-enter an overdose state from residual fentanyl in the body.
To counter renarcotization, naloxone must be given repeatedly and at significantly higher doses than fentanyl.
This approach may be achievable in a hospital; however, renarcotization is often not recognized outside a
medical setting and can lead to death. Thus, there is a critical need to develop a long acting MOR antagonist
formulation that can address renarcotization by providing the multi-hour protection.
The goal of this Phase I STTR project is to reformulate naloxone using FDA approved microencapsulation
technology into a long acting injectable (LAI) that can provide 12-24 hrs. of sustained antagonist activity in vivo.
Other attempts to address this issue by chemically modifying naloxone are likely to suffer significant regulatory
and technical risk. Consegna’s innovation is to employ its proprietary Computational Drug Delivery™ software,
called ADSR™, to perform in silico formulation optimization as well as to predict its in vitro dissolution and in
vivo pharmacokinetic behavior. Approval can be sought thru the 505(b)(2) accelerated regulatory pathway to
gain near-term entry into the market since the naloxone molecule is not modified and efficacy is not at risk.
This new long acting naloxone formulation, named CP216, will utilize an innovative design to address both
primary and secondary overdose (renarcotization) situations thru a combination of free form naloxone for
immediate effect and microencapsulated naloxone for sustained protection.
Our hypothesis is that sustained release of naloxone from microparticles, coupled with an immediate release of
free naloxone, can provide the therapeutics levels needed to reverse the overdose and prevent renarcotization.
To test this hypothesis, 1) design an appropriate microparticle formulation and assess the formulation’s
payload and release behavior in vitro, 2) evaluate the pharmacokinetics in an animal model, and 3) complete a
Quality-by-Design assessment for a Chemistry, Manufacturing, and Controls package. Consegna believes this
project has a significant potential to lead to the first safe and effective product to address renarcotization, and
will lead to a positive impact on public health.PROJECT NARRATIVE
There were more than 72,000 drug overdose deaths in 2017, most involving opioids. The goal of this STTR
Phase I project is to create a better antidote for opioid overdose and address a critical unmet medical need.
While naloxone is an effective opioid overdose antidote, it does not last long enough to be effective for synthetic
opioids such as fentanyl that have a long half-life. We plan to create a formulation that continuously releases
naloxone at therapeutic levels long enough to prevent renarcotization.

* Information listed above is at the time of submission. *

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