Funded Projects
Explore our currently funded projects. You may search with all three fields, then focus your results by applying any of the dropdown filters. After customizing your search, you may download results and even save your specific search for later.
Project # | Project Title | Research Focus Area | Research Program | Administering IC | Institution(s) | Investigator(s) | Location(s) Sort ascending | Year Awarded |
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1U01DA057862-01
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Development of PPL-138, a Novel Mixed NOP/Mu Partial Agonist for Treatment of Cocaine Use Disorder | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | PHOENIX PHARMALABS, INC. | TOLL, LAWRENCE R; LEVIN, FRANCES RUDNICK; LEVY, DANIEL | Woodscross, UT | 2022 |
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01)
NOFO Number: PAR-19-327 Summary: Currently no medications are approved by the U.S. Food and Drug Administration for psychostimulant (cocaine and methamphetamine) use disorder. This project will develop a novel opioid molecule (PPL-138) that blocks cocaine and methamphetamine self-administration in animal models and that lacks rewarding properties that could lead to addiction. This research will conduct manufacturing and safety studies to prepare for Phase 1 clinical trials to determine safety in human patients. |
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1UG3DA054825-01
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A novel and highly selective orexin 1 receptor antagonist for the treatment of patients with opioid use disorder | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | ASTRAZENECA PHARMACEUTICALS | INAMDAR, AMIR | Wilmington, DE | 2021 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092 Summary: In collaboration with Eolas Therapeutics and the NIH Blueprint Neurotherapeutics Network, AstraZeneca has developed a novel compound for treatment of opioid use disorder, AZD4041, which targets orexin 1 (OX1) receptors in the brain. In animal studies, AZD4041 reduced the motivation to consume opioids or nicotine, reduced relapse-like drug-seeking behaviors, and showed a favorable safety profile. The compound also has proven to be safe in an initial Phase 1 clinical trial in healthy human volunteers. This project will further evaluate the safety (e.g., respiratory depression profile) of AZD4041 in human volunteers, using multiple and increasing doses. Upon successful completion of these studies, the compound will be tested in a proof-of-concept efficacy study in patients with opioid use disorder. If this is successful, the compound will advance to larger Phase 2 and Phase 3 pivotal clinical trial to tests its effectiveness in the treatment of opioid use disorder. |
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1UG3DA048774-01
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Injectable naltrexone 2-month depot formulations | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | PURDUE UNIVERSITY | PARK, KINAM | West Lafayette, IN | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Naltrexone (NTX) has been proven as an important, safe, and effective therapy in helping patients overcome opioid addition and in preventing overdose. Unfortunately, the therapeutic potential of NTX has been blunted by poor adherence. To combat this issue, a system must be developed to deliver NTX for longer durations than are currently available with a more patient-friendly format. The goal of this research is to optimize and scale up our laboratory PLGA-based microparticle formulations of NTX delivery (either 2 months or 7–10 days) and bridge it to a Phase 1 clinical trial. This innovation will result in a more patient-friendly format consisting of less painful injections and improved release kinetics. PLGA-based drug delivery systems have been used successfully in a number of small-molecule products and are the most widely utilized and studied biocompatible polymer systems in controlled release. Thus, the regulatory and development hurdles with the FDA will be lower than with other novel excipients or technologies. The significance of this research and product development is that the final outcome of this project will ultimately provide a new, readily viable, essential tool to help patients overcome opioid dependence. |
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1UG3DA059270-01
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Long-Acting Biodegradable Buprenorphine Depots | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | PURDUE UNIVERSITY | OTTE, ANDREW | West Lafayette, IN | 2023 |
NOFO Title: Development of Medications to Prevent and Treat Opioid and/or Stimulant Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional)
NOFO Number: PAR-22-200 Summary: Buprenorphine is an effective treatment for opioid use disorder, but its use is limited due to the need for frequent dosing. This project will optimize the molecular features of an injectable, biodegradable, long-acting (3-month) buprenorphine implant that would not require surgical removal. The research aims to advance toward testing in human research participants. |
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1R21DA048074-01
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Prescription Opioid Formulation to Deter Extraction, Injection, Insufflation, and Smoking | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | PURDUE UNIVERSITY | Solorio, Luis | West Lafayette, IN | 2019 |
NOFO Title: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
NOFO Number: PA-18-489 Summary: This project aims to develop a novel abuse deterrent formulation (ADF) that will be uniquely designed to prevent abuse of the prescription pill. The study will focus on the development of the ADF with design aspects specifically focused on abuse through insufflation, smoking, injection, and taking multiple pills. The study will also validate the design by putting the pill through a rigorous test following the procedures outlined by the FDA Abuse-Deterrent-Opioids-Evaluation and Labeling guidelines. The study could result in the development of a novel ADF that will be resistant to a wide range of tampering, resulting in a safer formulation and pill design. |
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1UG3DA049599-01
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Development of a Potent and Highly Selective NaV1.7 Inhibitor for the Treatment of Acute Pain with the Goal of Reducing Opioid Use and Preventing Opioid Use Disorders | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | University of British Columbia | Hunter, John; Phillips, Anthony | Vancouver, BC, Canada | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 |
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1R01DA056608-01
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Endocannabinoid Targeting for Opioid Induced Respiratory Depression | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | University of Arizona | MILNES, TALLY MARIE (contact); VANDERAH, TODD W | Tucson, Arizona | 2022 |
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031 Summary: This research project will investigate the cannabinoid receptor 2 protein (CB2R) as a novel therapeutic target for opioid-induced respiratory depression caused by fentanyl, oxycodone, and heroin. This study will shed light on how the endocannabinoid system in the brainstem works to control breathing under normal conditions and during opioid-induced respiratory depression. The research aims to determine whether activation of the CB2R with a brain-penetrant CB2R-binding molecule is safe and clinically useful for treating opioid overdose prevention and reversal. This research will pave the way for discovering new medications that activate CB2R to reduce opioid-related deaths. |
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1UG3DA050303-01
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Development of an implantable closed-loop system for delivery of naloxone for the prevention of opioid-related overdose deaths | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Washington University | Rogers, John | St. Louis, MO | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Current opioid overdose treatment requires administration of naloxone by first responders, which requires timely identification of the overdose, the need for a rescue injection, and immediate availability of the medication. The development of a fail-safe treatment that would provide a life-saving dose of naloxone without the need for intervention by another party could significantly reduce mortality. The researchers aim to develop a new medical device comprising an implantable, closed-loop system that senses the presence of an opioid overdose, automatically administers a life-saving bolus injection of naloxone, and simultaneously alerts first responders. |
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1UG3DA047707-01
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Nalmefene Implant for the Long-Term Treatment of Opioid Use Disorder | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | TITAN PHARMACEUTICALS, INC. | BEEBE DEVARNEY, KATHERINE L | South San Francisco, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: There is a need for an opioid use disorder (OUD) treatment that can prevent relapse in detoxified subjects. Titan's proprietary subdermal implants can provide long-term, non-fluctuating therapeutic levels of drug continuously following a single office-based insertion procedure. The non-biodegradable solid matrix implant formulation virtually eliminates the risk of accidental drug dumping and associated serious toxicity, and its subdermal location assures patient compliance for the 6-month treatment duration. Nalmefene hydrochloride (nalmefene) is an opioid receptor antagonist approved for the management and reversal of opioid overdose. Prototype nalmefene implants inserted subdermally in rats delivered nalmefene continuously for months without any observable safety concerns. This proposed study will develop a 6-month implantable device that delivers nalmefene at a steady rate to prevent relapse to opioid dependence following opioid detoxification. This project will manufacture nalmefene implants, complete nonclinical safety and pharmacology studies, and conduct clinical studies in OUD subjects to support a New Drug Application. |
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1UG3DA050306-01
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1-Year Sustained Release Naltrexone Implant for the prevention of relapse to opioid dependence | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Delpor, Inc. | Martin, Francis | South San Francisco, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: There is a need for longer-acting prophylactic pharmacologic options for opioid use disorder (OUD) patients during maintenance therapy. This study tests a titanium implant loaded with a formulation of naltrexone and a naturally occurring carboxylic acid. The device is implanted subcutaneously with local anesthetic during an in-office procedure. The technology is based on a unique formulation that keeps the pH within the reservoir low and promotes passive diffusion of naltrexone. The benefits of the product include complete medication adherence for one year after administration, fewer relapses, smooth profile ensuring complete prophylaxis without sub-therapeutic plasma troughs, full reversibility, and similar efficacy with less drug exposure. This technology has been validated clinically with another drug and tested preclinically with naltrexone. This project will finalize the chemistry manufacturing and controls, produce IND supplies, conduct an IND-enabling safety study, and submit the IND. |
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1UG3DA058552-01
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Development of a Potent and Selective NaV1.8 Inhibitor for the Treatment of Acute and Chronic Pain with the Goal of Reducing Opioid Use and Preventing Opioid Use Disorders | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | SITEONE THERAPEUTICS, INC. | HUNTER, JOHN CURETON (contact); MULCAHY, JOHN VINCENT | South San Francisco, CA | 2023 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092 Summary: The sodium channel NaV1.8 is a promising target for the development of effective, non-addictive pain medications. Recent evidence from clinical studies indicates that medications that target NaV1.8 are effective at managing postoperative, neuropathic, and inflammatory pain, but with side effects and prohibitively high cost. This project will test the safety and compatibility in the body of an NaV1.8-targeted molecule, toward developing an effective, non-addictive, once daily oral medication for the treatment of acute postsurgical pain and chronic neuropathic. |
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1UG3DA057850-01
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Development of a Monoclonal Antibody to Reverse Overdose from Fentanyl and Its Analogs: From Manufacturing to Clinical Trials | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | UNIVERSITY OF WASHINGTON | PRAVETONI, MARCO; COMER, SANDRA D | Seattle, WA | 2022 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3)
NOFO Number: PAR-20-092 Summary: The widespread availability of fentanyl and other potent synthetic opioids has dramatically increased opioid-related fatal overdoses. This project will develop and manufacture immune molecules (monoclonal antibodies) to reverse and treat overdose from fentanyl by keeping it out of the brain. This research will advance promising results in animal studies (preventing and reversing fentanyl- and carfentanil-induced breathing problems and irregular heartbeat) to clinical testing in people with opioid use disorder and others at high risk of opioid overdose from accidental or deliberate exposure to fentanyl and fentanyl-like drugs. |
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1U01DA058541-01
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PDE7 Inhibitor for the Treatment of Cocaine Use Disorder | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | OMEROS CORPORATION | GAITANARIS, GEORGE | Seattle, WA | 2023 |
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327 Summary: Currently there are no effective treatments approved by the U.S. Food and Drug Administration for cocaine use disorder. This project will explore the use of a novel class of small molecules that selectively block the molecule phosphodiesterase 7 (PDE7). Past research suggests that the PDE7 class of compounds helps restore normal functions of the dopamine reward system altered by chronic exposure to cocaine. This research will use both preclinical and clinical research studies to develop and test a PDE7 blocker, toward development of the first oral treatment for cocaine use disorder. |
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1U01DA051071-01A1
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Process Development, Manufacturing, and Preclinical Evaluation of a Monoclonal Antibody for Fentanyl Overdose | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | CESSATION THERAPEUTICS, LLC | Bremer, Paul T. | San Jose, CA | 2020 |
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327 Summary: Opioid use disorder (OUD) is a significant public health problem in the United States. Particularly troubling is the rapid evolution of an opioid epidemic within the past decade, characterized by a surge in unintentional overdose deaths involving synthetic opioids, such as fentanyl. The current standard of care for opioid overdose is reversal with opioid antagonist naloxone. Naloxone is effective at reversing overdose from prescription opioids and heroin, but less effective when combating fentanyl, due to fentanyl?s high potency. Therapeutic monoclonal antibodies (mAbs) against fentanyl could overcome this problem by specifically preventing the drug from entering the central nervous system, averting overdose and attenuating opioid-induced respiratory depression. This study will develop and design of laboratory protocols needed to establish a Good Manufacturing Practice (GMP) process, quality assurance protocol, and stability profile for a new human mAb against fentanyl. Subsequent production of current GMP material will enable Good Laboratory Practice (GLP) toxicology studies in rats and dogs and eventually a Phase I/IIa clinical trial. This material will also be used in final opioid-induced respiratory depression studies in mice and non-human primates to confirm therapeutic efficacy of final drug product. If successful, these activities will enable filing for an investigational new drug application for this mAb candidate with the FDA. |
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1UG3DA049598-01
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Novel Therapeutics for Opioid Use Disorder in the Acute Overdose and Maintenance Settings | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Epiodyne, Inc. | Schmidt, William | San Francisco, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Opioid use disorder (OUD) and opioid overdose (OD) are major health issues. Breathing can be restored after OD by naloxone, but its short half-life can require multiple administrations to reverse OD, and OD symptoms may return after initial reversal if illicit opioids are still present after the effects of naloxone have worn off. Additionally, while the standard treatment of OUD with buprenorphine and methadone reduces relapse and mortality, access and adoption are limited by dosage forms, metabolic liabilities, and potential for misuse and diversion. This study seeks to develop chemically novel, potent mu-opioid receptor (MOR) antagonists and low- and mid-efficacy partial agonists. Current lead counts can outcompete opioid overdoses in preclinical models with a longer half-life, a key naloxone liability for treating OD. The potent, low-efficacy partial agonists add a low opioid tone, diminishing the aversive effects of pure antagonists. These, and the mid-efficacy partial agonists, are leads to maintenance therapeutics for OUD. |
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1UG3DA048375-01
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The long-term reduction of pain and opioid usage following mastectomy and tissue expander/implant surgery with a single administration of brivoligide, a non-opioid, disease-modifying drug candidate | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | ADYNXX, INC. | MAMET, JULIEN; MANNING, DONALD C | San Francisco, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: There is an urgent need to prevent and reduce opioid use disorder (OUD) by reducing the need for opioid analgesia and preventing the escalation of opioid dosing in patients at greater risk of using more opioids following surgery. Brivoligide is a non-opioid drug candidate that can alter the course of postoperative pain for patients most likely to suffer increased pain and utilize more opioids following surgery. A single administration of brivoligide at the time of surgery can reduce acute postoperative pain in these patients by 30 percent to 40 percent beyond what can be achieved with the current standard of care for at least 28 days and reduce opioid utilization by 40 percent over a 3-month period following surgery. This project will support the research necessary to achieve regulatory approval of brivoligide with a broad indication, which will initially focus on the reduction of postoperative pain following mastectomy, a soft-tissue surgery model suitable to detect long-term pain and opioid reduction benefits. Brivoligide appears to be a very promising pharmacotherapy with the potential to greatly contribute to stemming the tide in the opioid crisis. |
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1UG3DA050271-01
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R-methadone-TAAP/MPAR: an abuse deterrent methadone prodrug with overdose protection: Pre-Clinical Development and Phase 1 Clinical Trial | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Ensysce Biosciences, Inc. | Kirkpatrick, Lynn | San Diego, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Methadone is useful in the treatment of opioid dependence; however, methadone misuse and methadone-related fatalities have increased. Ensysce has created two complementary, novel technologies that can be applied to methadone. Their Trypsin Activated Abuse Protection (TAAP™) prodrugs are “enzyme-activated” to release clinically effective opioid drugs only when taken orally and exposed to the correct physiologic conditions, such as exposure to trypsin in the small bowel. Their multi-pill abuse resistance (MPAR™) feature involves in situ bioregulation of opioid delivery from the TAAP™ systems, enabling control over oral multi-dose pharmacokinetic profiles. It is envisaged that an R-methadone-TAAP™ prodrug would demonstrate similar reduced addiction liability as with other opioid-TAAP products. The objective of this proposal is to develop an R-methadone-TAAP™/MPAR™ drug through Phase 1 clinical studies and to translate R-methadone-TAAP™/MPAR™ results into humans, to ultimately reduce the misuse and oral overdose potential of methadone. |
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5UG3DA047682-02
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PF614 MPAR Abuse Deterrent opioid prodrug with overdose protection: Pre-Clinical Development and Phase 1 Clinical Trial | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | ENSYSCE BIOSCIENCES, INC. | Kirkpatrick,Lynn | San Diego, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: DA19-002 |
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1UG3DA047682-01
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PF614 MPAR Abuse Deterrent opioid prodrug with overdose protection: Pre-Clinical Development and Phase 1 Clinical Trial | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | ENSYSCE BIOSCIENCES, INC. | KIRKPATRICK, LYNN | San Diego, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Several abuse-deterrent opioid products (primarily formulations) are currently marketed or in clinical development, but they fall short of being resistant to abuse. Rather than abuse-deterrent formulations, this project, in partnership with Ensyce Biosciences, has created two complementary, novel technologies that control the release of known opioids. One technology delivers prodrugs — drugs that are not active until they have been exposed to the right conditions within the body, at which point they are gradually converted into active drugs, making them difficult to tamper with and reducing the potential for misuse. Another technology makes it so that taking increasing numbers of pills inhibits the process of converting prodrug into active drug, reducing the potential for overdose. This project aims to refine the development of these two technologies and work to combine them, and to translate promising animal results into human use. |
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1R01DA048417-01
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A novel opioid receptor antagonist for treating abuse and overdose | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | UNIVERSITY OF TEXAS HLTH SCIENCE CENTER | France, Charles P | San Antonio, TX | 2019 |
NOFO Title: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
NOFO Number: PA-18-484 Summary: Deaths from opioid overdose continue to rise; from 2015 to 2016, there was a 28 percent increase in the number of fatal overdoses. Currently available pharmacotherapies include MOR agonists (e.g., buprenorphine) and antagonists (e.g., naloxone), all of which suffer from specific and clear limitations. To address the main deficits in these treatments, the researchers will develop and optimize medications with longer duration of action that prevent and reverse the effects of opioids in a manner that is not surmounted by increasing doses of agonist. Their pilot studies in monkeys show that the pseudo irreversible MOR selective antagonist methocinnamox (MCAM) decreases heroin but not cocaine self-administration, decreases choice for remifentanil in a food/drug choice procedure, and reverses—as well as protects against—respiratory depression by heroin, with a single injection being effective for a week or longer. Bringing a medication like this to marketable fruition could significantly improve the treatment of OUD and save lives by providing insurmountable extended protection after rescue from overdose, including from ultra-potent fentanyl analogs. |
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1R01DA046532-01A1
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Evaluation of drug mixtures for treating pain: behavioral and pharmacological interactions between opioids and serotonin agonists | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | UNIVERSITY OF TEXAS HLTH SCIENCE CENTER | Maguire, David Richard | San Antonio, TX | 2019 |
NOFO Title: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
NOFO Number: PA-18-484 Summary: Opioids remain the gold standard for treating moderate to severe pain, but their use is limited by numerous adverse effects, including tolerance, dependence, abuse, and overdose. Adverse effects could be avoided by combining an opioid with another drug, such that smaller doses of the opioid (in combination with another drug) produce the desired therapeutic effect. Direct-acting serotonin type 2 (5-HT2) receptor agonists interact in a synergistic manner with the opioid morphine to produce antinociceptive effects, suggesting a 5-HT2 receptor agonist could be combined with small amounts of an opioid to treat pain, thereby lowering the risk associated with larger doses. Unfortunately, very little is known about interactions between 5-HT2 receptor agonists and other opioids. The proposed studies will evaluate the therapeutic potential of mixtures of opioids and 5-HT2 receptor agonists using highly translatable and well-established procedures to characterize the antinociceptive, respiratory-depressant (overdose), positive-reinforcing (leading to misuse), and discriminative-stimulus (subjective) effects of drug mixtures as well as the impact of chronic treatment on the development of tolerance to and physical dependence on opioids. If successful, these studies will provide proof-of-concept for this innovative approach to pain treatment and evaluate the utility of targeting 5-HT receptors for analgesic drug development. |
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1UG3DA048387-01A1
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Methocinnamox (MCAM): A novel ?-opioid receptor antagonist for opioid use disorders | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | University of Texas Health Science Center San Antonio | Woods, James | San Antonio, TX | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: MCAM is a novel opioid antagonist that can be used for opioid overdose reversal and has advantages over naloxone, including a pseudo-irreversible interaction with the ?-opioid receptor and a longer duration of action. Studies in animal models demonstrate MCAM’s long duration of action against the reinforcing and respiratory-depressant effects of remifentanil and heroin, indicating that could be a better treatment option for opioid use disorder. This project studies the pharmacodynamics of MCAM through animal toxicity and safety studies to establish the necessary and sufficient conditions from which to establish MCAM’s safety and antagonist activity in animals and humans. MCAM may be able to prevent all actions of any ?-receptor opioid drug in humans for a longer period of time than any other antagonist given acutely. |
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1UG3DA048338-01A1
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A Long-Acting Bioabsorbable Naltrexone Subcutaneous Implant for Opioid Use Disorder | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | DRUG DELIVERY COMPANY, LLC, THE | COHEN, STEVEN M; BENNER, JEFFREY | Salisbury, MD | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Naltrexone (NTX) has proven to be an important, safe, and effective therapy for helping patients overcome opioid use disorders (OUD) and for preventing overdose. Unfortunately, the therapeutic potential of NTX has been blunted by poor adherence. To combat this issue, a system must be developed to deliver NTX for longer durations than currently available and with a more patient-friendly format. To address this problem, we will develop a long-acting and bioabsorbable NTX subcutaneous implant for the treatment of OUD. The proposed research will (a) determine the optimal chemical preparation of NTX inside the implant, (b) optimize the composition and porosity of the drug delivery substrate, and (c) refine the surgical procedure and instrumentation to be used during implantation. Once the safety and efficacy of this novel NTX implant is established, we will conduct the necessary clinical trials. The proposed study is highly relevant to and complementary of other efforts, either in consideration or already deployed to stem the tide of the lingering opioid crisis. If successful, this solution has the potential to enhance health, lengthen life, and reduce illness and disability for those suffering from OUD. |
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1UG3DA054785-01A1
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Development of Specific Mu Opioid Receptor Antagonists to Reverse the Acute and Chronic Toxicity of Fentanyls | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Virginia Commonwealth University | ZHANG, YAN | Richmond, Virginia | 2022 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092 Summary: Fentanyl and its analogs are synthetic opioids that are 100 to 10,000 times more potent than morphine. Overdose from these opioids is extremely dangerous due to their ultra-potency and longer half-life than naloxone, the front-line treatment for fentanyl overdose. This research study will develop novel mu opioid receptor antagonists that bind to the same receptor as the opioid drugs and specifically counteract fentanyl and its analogs, thereby reversing the drugs’ acute toxicity more effectively and with fewer side effects than current treatments. The researchers will characterize novel fentanyl derivatives, identify promising compounds, and pursue preclinical development of these compounds as novel reversal agents against the acute toxicity of fentanyl. The goal is to file an Investigational New Drug application with the U.S. Food and Drug Administration. |
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1UG3DA050311-01
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Mu Opioid Receptor Modulator Development to Treat Opioid Use Disorder | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Virginia Commonwealth University | Zhang, Yan | Richmond, VA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: There is a need to develop a mu-opioid receptor (MOR) treatment with enhanced therapeutic effects and reduced undesirable effects. Recently, several highly selective and potent MOR modulators have been identified as novel leads for opioid use disorder treatment. They all showed more promising pharmacological profiles compared to other known drugs in this category. The current proposal will focus on further development of these leads for preclinical IND-enabling studies and dynamic drug discovery and development pipeline construction. This project plans to further validate therapeutic profiles of the current leads with self-administration and pharmacokinetic studies and expand the small-molecule library to build a dynamic drug discovery and development pipeline. Preclinical IND-enabling studies on the identified lead(s) will be conducted, and in vivo pharmacokinetics and pharmacodynamics profiles of the new hits will be compared with current leads to define the next generation of lead compound(s). |