Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1R01DA057120-01
Characterization, Optimization, and Development of Dual mGlu2/3 Positive Allosteric Modulators 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 Sanford Burnham Prebys Medical Discovery Institute COSFORD, NICHOLAS DAVID; VELICELEBI, GONUL La Jolla, CA 2022
NOFO Title: Strategic Alliances for Medications Development to Treat Substance Use Disorders (R01Clinical Trial Optional)
NOFO Number: PAR-19-318
Summary:

Given recent increases in co-use of opioids and methamphetamine, there is a dire need for novel treatment strategies that prevent relapse to drug use in both opioid use disorder (OUD) and methamphetamine use disorder (MUD). The localization of certain receptors for the neurotransmitter glutamate—metabotropic glutamate receptor subtypes 2 and 3 (mGlu2/3)—and the mechanism through which they transmit signals, strongly suggest that activation of both of these receptors will effectively treat multiple symptoms that contribute to relapse, such as responsiveness to drug cues, physical withdrawal symptoms, neuroinflammation, and sleep disturbances. This project seeks to evaluate molecules that can activate mGlu2/3 receptors without binding to the same site as glutamate (i.e., positive allosteric modulators) as a novel pharmacological treatment for preventing relapse to OUD. The research also will examine the potential of such modulators for treating MUD.
1R21DA056740-01
Recruiting Active Expiration to Overcome Opioid-Induced Persistent Apnea Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of California, Los Angeles FELDMAN, JACK L Los Angeles, CA 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R21 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-032
Summary:

Prescription opioids provide pain relief, but overdose can be fatal because opioids also depress breathing through opioid-induced persistent apnea, when breathing stops. This research will determine whether targeted activation of a specific, opioid-insensitive brain region that triggers exhalation can increase tolerance to fentanyl-induced apnea. The research also seeks to identify the receptors responsible for this exhalation, which could be targets for new medications that prevent the negative impact of opioids on breathing. This research lays the groundwork for more preclinical and translational studies to prevent opioid-induced persistent apnea. 
1R01DA056673-01
Targeting Tiam1-Mediated Synaptic Plasticity for the Relief of Opioid Tolerance Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Baylor College of Medicine LI, LINGYONG (contact); TOLIAS, KIMBERLY Houston, TX 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:

Chronic opioid use results in tolerance, a primary driver for opioid misuse and overdose that directly contribute to increased morbidity and mortality. Changes in neuronal connectivity known as synaptic plasticity are a key determinant of opioid tolerance, but the underlying molecular mechanisms remain unclear. Tiam1 is a protein known to control the development of nerve cells and their connections and is also involved in morphine-induced neuronal changes. This research will examine Tiam1-mediated synaptic plasticity underlying opioid tolerance and validate Tiam1 as a potential therapeutic target for prevention of tolerance development.
1R01DA056675-01
Domain-Specific Inhibition of Angiotensin-Converting Enzyme as a Therapeutic Strategy 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 Minnesota ROTHWELL, PATRICK (contact); MORE, SWATI S Minneapolis, MN 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:

Novel treatments for opioid use disorder are urgently needed. Previous research has shown that angiotensin-converting enzyme (ACE) can control levels and activity of natural, “endogenous,” opioids in a way that might reduce the rewarding effects of opioids like fentanyl. ACE inhibitors have been used to treat hypertension for decades, with no evidence of addiction or dependence. This research will evaluate ACE effects on endogenous opioids toward generating new, domain-specific ACE inhibitors with optimized properties for treating opioid use disorder. The research will also test the behavioral impact of these compounds in preclinical models of opioid use disorder. 
3UG3DA048502-01A1S2
Non-invasive vagal nerve stimulation in 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 EMORY UNIVERSITY BREMNER, JAMES DOUGLAS Atlanta, GA 2021
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107
Summary:

This research will expand the understanding of the effects of non-invasive vagal nerve stimulation on patients with opioid use disorder by examining the relationship between nerve stimulation and treatment, respiratory physiology, withdrawal symptoms, and relapse. Additionally, these relationships will be added to existing algorithms and equipment being developed by the Inan Research Lab at the Georgia Institute of Technology. Collecting and determining the quality of conventional respiration signals, as well as collecting high-resolution impedance based respiratory measurements, will help to determine the impact of non-invasive vagal nerve stimulation on breathing and lung function in people with opioid use disorder, toward development of a profile of physiological effects of non-invasive vagal nerve stimulation during opioid withdrawal.
1UG3DA052166-01A1
CVL-354, a kappa opioid receptor antagonist for treatment of opioid use disorder, withdrawal and relapse Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA CEREVEL THERAPEUTICS, LLC IREDALE, PHILIP Cambridge, MA 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:

Kappa opioid receptors (KOR) are expressed in brain areas that control reward, motivation, and anxiety. Upon opioid drug withdrawal and abstinence, dysregulated KOR signaling can result in aversive physical and affective states that are a major driver of relapse. Preclinical data have demonstrated that antagonism of KOR can reduce the physical symptoms of opioid withdrawal. Currently, the alpha 2-adrenergic agonist lofexidine is the only approved therapy for the mitigation of the physical symptoms of opioid withdrawal but it is only modestly effective and can have significant unwanted side effects. Cerevel Therapeutics has identified a novel selective KOR antagonist, CVL-354, with unique properties and good preclinical safety margins. This project will assess this drug in early human safety/pharmacokinetics and occupancy studies. Future studies will then be able to assess efficacy of this drug in acute opioid withdrawal.
1UG3DA054825-01
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.
1UG3DA053123-01
Bacteriophage virus-like particle vaccines for fentanyl and heroin 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 NEW MEXICO HEALTH SCIS CTR CHACKERIAN, BRYCE C Albuquerque, NM 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:

Opioids account for nearly 70 percent of overdose deaths in the United States, with fentanyl and heroin use the most common causes. The goal of this project is to create a vaccine to elicit serum antibodies that bind and sequester the drug in the blood, preventing it from crossing the blood-brain barrier where it acts on the central nervous system. Current opioid vaccine strategies require multiple boosts and months to reach peak titers, the level of antibodies in a blood sample, and have yet to show protection against lethal overdose. In this project, researchers will use a bacteriophage virus-like particle vaccine platform to engineer and test the effectiveness of a combined vaccine to elicit high titer antibodies quickly to protect against lethal overdose from fentanyl or heroin.
1UG3DA054799-01
Development of Lofexidine as a First-line Non-Opioid Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA USWM, LLC GULLO, KRISTEN LEANN Louisville, KY 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:

The nation’s opioid epidemic remains a public health emergency, marked by high rates of opioid use and misuse among adults and a correlated rising incidence of neonatal opioid withdrawal syndrome (NOWS) in infants exposed to opioids before they are born. There are currently no pharmacotherapies approved by the Food and Drug Administration (FDA) for the treatment of NOWS. This research will complete manufacturing and clinical trial activities to evaluate and support FDA approval of a pediatric-appropriate formulation of lofexidine, a non-opioid medication approved for mitigation of opioid withdrawal symptoms in adults, as a first line-therapy in NOWS patients through two clinical trials to (1) identify an optimal dosing regimen of lofexidine for treatment of NOWS, and (2) evaluate the risks and benefits of its use in improving withdrawal symptoms, limiting infant exposure to other off-label narcotic medications and shortening the infant’s overall stay in the hospital.
1UG3DA052173-01A1
Combating opioid addiction using CVL-936, a novel D3/D2 receptor antagonist Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA CEREVEL THERAPEUTICS, LLC CHAKILAM, ANANTHSRINIVAS RAO Cambridge, MA 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:

Opioid use and addiction affects more than 2 million Americans and contribute to a large proportion of all drug overdose deaths. Current treatments for opioid use disorder (e.g., methadone and buprenorphine) are not always effective, may be misused, and can have side effects that discourage treatment continuation. Therefore, Cerevel Therapeutics is evaluating a novel compound, CVL-936, which targets brain molecules called dopamine D3 receptors. These receptors are involved in the brain’s reward and relapse pathways and are present in higher levels in people with addictions. In animal studies, the molecule reduced self-administration of nicotine and fentanyl, including in relapse situations. The project will test the safety and tolerability of CVL-936 in animals and healthy humans and will examine its effectiveness in reducing craving in people with opioid use disorder.
1UG3DA050942-01A1
An Intranasal GDNF Gene Therapy for Opioid Relapse Reduction Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA NORTHEASTERN UNIVERSITY WASZCZAK, BARBARA LEE Boston, MA 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:

There are currently no effective non-opioid-based pharmacotherapies for treatment of opioid use disorder (OUD). Glial cell line-derived neurotrophic factor (GDNF) is a beneficial protein normally present in low levels in the adult brain, and there is strong evidence that it has clinical potential as a therapy for OUD and relapse reduction. Researchers have developed a non-invasive approach that bypasses the blood-brain barrier to increase levels of GDNF using intranasal administration of gene nanoparticles that make GDNF protein within the brain. This project will test whether this intranasal GDNF gene therapy can suppress drug craving and reduce the tendency to start using a drug again after a period of abstinence in experimental models, thus providing a long-term therapeutic strategy for reducing opioid craving and preventing relapse.
1UF1DA053806-01A1
Development of a novel OTC naloxone product to be affordably priced and widely accessible Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA POCKET NALOXONE CORP. KIM, SONNIE Bethesda, MD 2021
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327
Summary:

Naloxone is a safe and effective opioid antagonist, but currently available products are burdened with high cost and limited accessibility due to a need for a prescription or being kept behind-the-counter. In response to the FDA putting out an unprecedented call for an over the counter naloxone product, Pocket Naloxone Corp. is developing a novel intranasal delivery method for naloxone intended to be low-priced and widely accessible. This project will culminate in a New Drug Application to the FDA for over-the-counter approval to meet the urgent need for widespread access to a reliable, easy-to-use naloxone product for use in an emergency by non-medical individuals.
1UF1DA054817-01A1
Preclinical Development of Novel Dual OXR/KOR Antagonists for Treatment of Substance Use Disorder Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA HAGER BIOSCIENCES, INC. BUTERA, JOHN A Bethlehem, PA 2021
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327
Summary:

Substance use disorder (SUD) is a serious public health and socioeconomic burden. In this project, researchers will develop novel drug compounds that dually target orexin receptors and kappa opioid receptors, which have both been implicated in SUD. The compounds will then be tested for effectiveness in preclinical models of SUD, including models of cocaine, methamphetamine, and fentanyl use. This research has the potential to provide highly impactful and innovative treatment options for SUD via simultaneous modulation of multiple signaling pathways.
1R61HL156248-01
Intranasal Leptin as A Novel Treatment of 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 NHLBI JOHNS HOPKINS UNIVERSITY POLOTSKY, VSEVOLOD Y Baltimore, MD 2020
NOFO Title: HEAL Initiative: Pharmacotherapies to Reverse Opioid Overdose Induced Respiratory Depression without Central Opioid Withdrawal (Target Validation and Candidate Therapeutic Development (R61/R33 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-20-031
1U01DA046430-01A1
Efficacy of buprenorphine and XR-naltrexone combination for relapse prevention in 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 NEW YORK STATE PSYCHIATRIC INSTITUTE Bisaga, Adam New York, NY 2020
NOFO Title:
NOFO Number: PA18-345
1UG3DA051383-01A1
Brexpiprazole as an Adjunctive Treatment to Buprenorhpine 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 OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC. Forbes, Andy Princeton, NJ 2020
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:

Over 2 million Americans have an Opioid Use Disorder (OUD) and the risks associated with misuse of opioids have prompted a public health crisis. There are three effective FDA-approved drugs for medication assisted treatment (MAT) of OUD. However, while MAT can reduce overall OUD related mortality by as much as fifty percent, relapse and treatment discontinuation are common within the first 5 to 12 weeks of MAT. As longer treatment retention is correlated with better long-term outcomes, the development of an adjunctive medication to alleviate key psychiatric symptoms associated with treatment failure would address an important unmet need. This study seeks to evaluate the safety and efficacy of brexpiprazole as adjunctive treatment to buprenorphine/naloxone in OUD. If successful, this study could enhance the effectiveness of OUD treatments by extending the duration of treatment, thereby reducing the likelihood for relapse and overdose.
1R61HL156240-01
Treatment of Fentanyl Overdose-Induced Respiratory Failure by Low-Dose Dexmedetomidine Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NHLBI PENNSYLVANIA STATE UNIV HERSHEY MED CTR HAOUZI, PHILIPPE A Hershey, PA 2020
NOFO Title: HEAL Initiative: Pharmacotherapies to Reverse Opioid Overdose Induced Respiratory Depression without Central Opioid Withdrawal (Target Validation and Candidate Therapeutic Development (R61/R33 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-20-031
1UG3DA050923-01
AMPA Antagonism: A Novel Pharmacology for Launching Recovery from Opioid Addiction Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS Chambers, Robert Indianapolis, IN 2020
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:

The excruciating multiday experience of opioid withdrawal syndrome (OWS), is exacerbated by the opioid antagonist drugs naloxone and naltrexone. This industry-academia collaboration will explore the potential of the glutamate AMPA receptor antagonist Tezampanel (TZP). Animal studies have shown reduced hyperactivity in brain circuits involved in OWS, without relying on direct stimulation or antagonism of the opioid system ,and has already been delivered to over 500 human subjects and found to be safe for a potential migraine indication. This proposal will build up the evidence needed to apply for and conduct open label and blinded placebo-controlled human trials of TZP safety and efficacy for OWS. If successful, this project will allow planning for a pivotal registration trial for TZP for OWS, and as a transitional treatment to long-term recovery on naltrexone and help us stem the tide of the opioid crisis.
1UG3DA048502-01A1
Non-Invasive Vagal Nerve Stimulation in Patients with 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 EMORY UNIVERSITY Bremner, James Douglas Atlanta, Georgia 2020
NOFO Title:
NOFO Number: PAR18-494
1U01DA051071-01A1
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.
1UG3DA051392-01
Evaluation of the Safety and Efficacy of a New Oral Small Molecule GABA-B Receptor Positive Allosteric Modulator (PAM) as an Add-on Maintenance Therapy for Opioid Use Disorder (OUD) Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA ASTELLAS PHARMA GLOBAL DEVELOPMENT, INC. Blahunka, Paul NORTHBROOK, IL 2020
NOFO Title:
NOFO Number: DA19-002
1UG3DA052282-01
NOP Receptor Antagonist for OUD Pharmacotherapy 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 MED BR GALVESTON Cunningham, Kathryn Galveston, TX 2020
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:

Medication-based treatment for opioid use disorder OUD aids in reducing mortality, opioid withdrawal, intake and opioid-seeking behaviors, however there is a clear need to increase the armamentarium of therapeutics for OUD. The ?non-classical? NOcicePtin receptor (NOPr) binds the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ) and is a promising target based on the evidence for its function in the regulation of the rewarding and motivational effects of opioids and alcohol. This study plans to assess the ability of the novel and selective NOPr antagonist BTRX-246040 to block oxycodone intake without abuse liability, and to suppress oxycodone withdrawal and relapse-like behaviors in rats. The study will also determine Drug Metabolism and Pharmacokinetics interactions (DMPK) between oxycodone and BTRX-246040 and brain penetrability in male and female rats. If successful, these preclinical studies will be followed by a Phase 1 clinical trial in non-treatment seeking OUD participants. These investigations will advance the prospects of validating a novel medication for OUD.
1UG3DA047707-01
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.
1UG3DA047711-01
Phase 1a/1b Clinical Trials of Multivalent Opioid Vaccine Components Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA NEW YORK STATE PSYCHIATRIC INSTITUTE COMER, SANDRA D; PRAVETONI, MARCO New York, NY 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:

The current studies are designed to examine a novel approach to treating OUD, namely use of a vaccine (OXY-KLH) targeted against oxycodone, one of the most commonly misused prescription opioids, and a vaccine (M-KLH) targeted against heroin/morphine. The researchers will evaluate the safety, immunogenicity, and preliminary efficacy of OXY-KLH and M-KLH. Overall, the proposed studies will provide a great deal of information about the safety and potential efficacy of the vaccines in reducing the addiction liability of opioids, which will be administered in a controlled laboratory setting. If the outcomes of the proposed studies with OXY-KLH and M-KLH are favorable, development of the bivalent vaccine (OXY-KLH plus M-KLH) that will target oxycodone and heroin will proceed. The long-term goal of this research is to develop a multivalent vaccine directed against oxycodone, heroin, and other relevant opioids.
1UG3DA048767-01
Development of a Soluble Epoxide Hydrolase Inhibitor to Spare or Replace Opioid Analgesics Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Eicosis, LLC Hammock, Bruce Davis, 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:

EicOsis is developing a first-in-class analgesic with efficacy against neuropathic pain that will reduce or replace the need for opioids and thus potentially prevent opioid use disorder (OUD). The target of the small molecule inhibitor EC5026 is the soluble epoxide hydrolase, a master regulatory enzyme that modulates the activity of endogenous bioactive lipids. The study will reach the next steps in clinical human clinical trials with EC5026 through additional preclinical studies to expand the efficacy into models of chronic pain conditions. Additionally, detailed pharmacokinetic, metabolism, and distribution studies are proposed that will provide the required information to optimize drug formulation and for advanced clinical trials examining efficacy in humans. EicOsis is meeting current development goals, and EC5026 is well positioned to meet the urgent need of reducing opioid use.