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.

Reset
Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1UG3DA048774-01
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.
1R21DA048074-01
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.
1UG3DA048371-01
Development of Next-generation Pharmacotherapy 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 ASTRAEA THERAPEUTICS, LLC ZAVERI, NURULAIN T Mountain View, 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:

Although effective, current pharmacotherapies for opioid use disorder (OUD) present serious limitations. For example, methadone, a mu opioid receptor (MOP) full agonist, has significant abuse liability and causes withdrawal after chronic use, while buprenorphine (Bup), an MOP partial agonist and kappa opioid receptor (KOP) antagonist, produces limited respiratory depression and is less effective than methadone in reducing drug use, craving, and relapse. To address the limitation of currently available MATs, this project uses a phased plan that will fast-track the IND development of a next-generation medication for OUD based on small-molecule compounds targeting the nociception opioid receptor (NOP)—with no misuse or dependence liability—that have shown promising efficacy in reducing oxycodone intake in rhesus monkeys trained to self-administer, with efficacies similar to that of buprenorphine. The project’s ultimate goal is to file an IND application for an NOP agonist as a promising new approach to treat illicit and prescription OUD that may offer an alternative to buprenorphine.
1UG3DA047925-01
Development of a 3-month implantable depot pellet of Naltrexone for the 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 BIOCORRX, INC. BRAR, BALBIR Anaheim, 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:

The opioid antagonist naltrexone (NTX) is a proven treatment for opioid use disorder (OUD); however, lack of adherence is a serious limitation that has prevented NTX from reaching its maximum therapeutic potential. To address this limitation, BioCorRx is developing BICX102, a subcutaneous solid depot pellet of NTX, a single implantation of which can provide continual blockade of opioid receptors for up to 3 months. This can prevent patients from being adversely affected by almost any opioid relapse event, while improving efficacy and adherence to behavioral programs that support long-term management and recovery. This proposal comprises the steps required to achieve FDA approval. Successful development of BICX102 would result in a safe and effective 3-month subcutaneous depot pellet/implant containing NTX (1,000 mg) that would be far less reliant on patient compliance.
1UG3DA050325-01
Use of a GLP-1 Agonist to Treat Opioid Use Disorder in Rats and Man Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Pennsylvania State University Hershey Medical Center Grigson, Patricia Hershey, PA 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:

High relapse rates among people with opioid use disorder (OUD) indicate that addiction involves appetitive pathways. Peripheral stimulation of the glucagon-like peptide-1 receptor (GLP-1R) “satiety” pathway could reduce heroin seeking and taking. Pretreatment with a GLP-1R agonist reduces heroin taking, seeking, and drug-induced reinstatement in rats. This project tests whether GLP-1R agonists can reduce relapse in humans with OUD. A pilot study will be conducted to determine whether once-daily treatment with the shorter acting GLP-1R agonist, liraglutide, can safely and effectively reduce cravings among OUD patients. Animal models will be used to test the efficacy and safety of a longer-acting GLP-1R agonist, semaglutide, and then a clinical trial will be conducted to test whether semaglutide will reduce relapse and use in animal models. If successful, the study will show that treatment with GLP-1R agonists can safely and effectively reduce opioid craving, seeking, and relapse.
1UG3DA049694-01
Combining Pregabalin with Lofexidine: Can it Increase the Success of Transition to Naltrexone? Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Pennsylvania Kampman, Kyle Philadelphia, PA 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:

Extended-release naltrexone (XR-NTX) reduces overdose risk; however, transitioning to XR-NTX requires detoxification, which is a major hurdle. Non-opioid detoxification with an alpha-2 adrenergic receptor agonist, such as lofexidine, may shorten detoxification time, but it does not reduce the subjective effects of withdrawal. Pregabalin potentiates the activity of glutamic acid decarboxylase, inhibits calcium influx and release of excitatory neurotransmitters, raises GABA levels, and is approved for neuropathic pain, for fibromyalgia, and as an adjunctive therapy for adults with partial onset seizures. The study will test whether pregabalin can be combined with lofexidine to better reduce the subjective effects of opioid withdrawal than lofexidine alone and increase the proportion of patients that transition to XR-NTX. Such a dosing combination could lower the detoxification hurdle for patients who are interested in antagonist treatment or who are in settings where it is unavailable or difficult to access.
1UG3DA047708-01
Development of a safe and effective novel mechanism analgesic to treat moderate to severe pain with low or absent abuse liability. Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA ARTYS BIOTECH, LLC LARK, MICHAEL WILLIAM; ZADINA, JAMES E Plymouth Meeting, PA 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:

Chronic pain affects an estimated 100 million Americans, or one third of the U.S. population, and it is the primary reason Americans are on disability. Although many treatments are available for pain, the most potent class of analgesics relies on opioid analogs, whose limitations and well-known adverse effects have contributed to the present opioid crisis. New pharmacotherapies for pain management are sorely needed. MTX1604, a synthetic endomorphin analog, has emerged as a highly effective analgesic that exhibits reduced reward potential and respiratory suppression, and a robust duration of efficacy in a variety of validated animal models of acute, neuropathic, inflammatory, post-operative, and visceral pain. This project will generate additional preclinical characterization data of MTX1604 and advance clinical development toward FDA approval. If successful, this medication development project could offer patients a novel non-addictive, potent, and safe analgesic and thus have a direct impact on the opioid crisis.
3UG3DA048351-01S1
A Phase I/IIa Clinical Trial Testing the Safety and Immunogenicity of a Heroin Vaccine and its Efficacy Against Morphine Challenge. Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA HENRY M. JACKSON FDN FOR THE ADV MIL/MED MATYAS, GARY R Bethesda, 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
1UG3DA048386-01
Vaccines for fentanyl and its derivatives: A strategy to reduce illicit use 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 MINNESOTA PRAVETONI, MARCO Minneapolis, MN 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 United States has seen dramatic increases in fatal overdoses due to heroin, counterfeit prescription drugs, and cocaine adulterated with fentanyl or fentanyl-like analogs. Current medications may not be sufficient to address the opioid overdose epidemic. As a complementary strategy, the researchers plan to develop vaccines against fentanyl and fentanyl-like compounds to reduce their abuse liability and the growing incidence of fatal overdoses. This research team has already developed vaccines against heroin and oxycodone that stimulate the production of antibodies effective in reducing opioid distribution to the brain, opioid-induced behaviors, and opioid-induced respiratory depression and have identified a promising fentanyl vaccine candidate cued up for optimization. Successful completion of an anti-fentanyl vaccine development project could offer a long-lasting, safe, and cost-effective intervention complementary to medication-assisted treatment (MAT) and may reduce overdoses in opioid users as well as protect people in professions (e.g., law enforcement, airport security, postal workers) at risk of accidental exposure to fentanyl and fentanyl analogs.
1UG3DA048234-01
Development of a novel drug for treating 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 NIRSUM LABORATORIES, INC. TUSCHE, MICHAEL; SHAH, NIKEJ 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 ongoing epidemic of opioid use disorder (OUD), overdose, and death is unprecedented. Available pharmacologic therapies for OUD have failed to stem the tide, plagued by poor adherence and retention, the principal factors associated with relapse and treatment failure. More than 80 percent of individuals with OUD are untreated. More treatment options are needed. This proposal seeks to develop a better antagonist-based OUD pharmacotherapy for populations highly motivated to achieve abstinence, such as military personnel, criminal justice clients, and the currently employed. A series of novel and proprietary small molecules will be designed and synthesized to address the adherence problem by inducing effective opioid antagonism with a single injection lasting at least 2 months, and up to 4 months or more. The goal of this project is to advance to Phase 3 clinical trials toward FDA approval of our lead compound. If successful, this project could lead to a novel therapeutic with superior adherence and retention, resulting in a significant public health impact by reducing rates of relapse, overdose, and death.
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.
1UG3DA047682-01
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.
1UG3DA048743-01
Advancing KNX100 for the treatment of opioid withdrawal: preclinical efficacy and toxicology, and a phase 1 clinical program. Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Kinoxis Therapeutics, PTY LTD MacGregor, Iain Camberwell, Vic, Australia 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:

Kinoxis has developed a novel small-molecule lead, KNX100, that reduces the severity of opioid withdrawal symptoms in preclinical animal models of opioid use disorder (OUD). KNX100 was discovered from a phenotypic screen of compounds derived from a fragment-based drug discovery program targeting the brain oxytocin system. KNX100 has a favorable pharmacokinetic and safety profile and has undergone testing for efficacy signals in two rodents and two non-human primate species. The proposed activity is to progress the development of KNX100 to treat opioid withdrawal in OUD. The overall objective of the project is to establish the safety and tolerability of KNX100 to enable human efficacy testing to commence in patients requiring treatment for opioid withdrawal. The long-term objective for this development program is to generate human efficacy data to support KNX100 as a potential treatment for opioid withdrawal symptoms and ultimately enable a New Drug Application to the FDA.
1UG3DA047717-01
MOR/DOR Heterodimer Antagonists: A Novel Treatment for Opioid Dependence Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA WASHINGTON STATE UNIVERSITY MORGAN, MICHAEL M Pullman, WA 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:

Tens of thousands of people die each year from opioid overdose. Many of these people began taking opioids for pain. A critical treatment goal is to reduce the development of opioid dependence either by enhancing opioid analgesia so lower doses can be used or by blocking withdrawal symptoms. Current pharmacological treatments in these two categories, although effective, present serious limitations. The recent finding that reducing the signaling through mu-delta opioid heterodimers appears to enhance opioid antinociception and reduce dependence suggests that a blocker of mixed mu-delta receptors (MDOR antagonist) could be effective in reducing dependence by limiting opioid tolerance and preventing opioid withdrawal. This research group has developed a compound with that characteristic, called D24M, which preliminary studies have shown could reduce opioid dependence by enhancing opioid antinociception, reducing opioid tolerance, or directly inhibiting opioid withdrawal. They propose to extend this research by investigating whether it can reduce chronic pain in an animal model that mimics the clinical situation of pain patients who transition to dependence. If these studies are successful, they could lead to the development of an optimized drug ready for Investigational New Drug (IND) application and enable translational and clinical testing.
1UG3DA049598-01
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.
1UG3DA048387-01A1
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.
3UG3DA047720-01S1
Evaluation of safety and pharmacokinetics of naltrexone implant 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 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

New medication treatment approaches are needed to help address the severe epidemic of opioid use disorder (OUD) and opioid overdose deaths in the U.S. Currently available medications, such as methadone, buprenorphine, and extended release injection naltrexone (XR-NTX; trade name: Vivitrol), are highly efficacious, but their effectiveness in practice is limited by poor adherence, with many patients stopping treatment prematurely and relapsing. The goal of this proposal is to develop an innovative long-acting subcutaneous implanted formulation of naltrexone, the O’Neil Long-Acting Naltrexone Implant (OLANI), toward FDA approval. Expected to produce naltrexone blood levels sufficient to block the effects of opioids for 6 months after implant, OLANI circumvents the need for adherence to monthly injections with XR-NTX and could represent an important new addition to the medical armamentarium for treatment of OUD.
1UG3DA048388-01
Cannabidiol Effects on Craving and 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 INSYS DEVELOPMENT COMPANY ELKASHEF, AHMED Chandler, AZ 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:

To tackle the national public health emergency posed by opioid misuse, addiction, and overdose deaths, the development of effective new medications and the FDA drug approval process must be accelerated. In response to this call, INSYS Development Company, Inc. (INSYS) has developed a cannabidiol (CBD) oral solution that shows promise as a novel medication for prevention of relapse that addresses one of the five opportunities specified in the HEAL Initiative to improve treatment options. The first phase of this project involves clinical trials of CBD on cue-induced cravings, modulation of withdrawal, alterations of negative affect states, relapse to opioid use, and treatment retention in patients with OUD receiving buprenorphine treatment in a residential drug treatment facility. The findings from this phase will inform further studies in an outpatient setting. If successful, this project could advance to the development of a new monotherapy for the treatment of OUD.
1UG3DA049599-01
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
1R34DA046635-01A1
Treatment of chronic low back pain with transcutaneous auricular vagus nerve stimulation Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA MASSACHUSETTS GENERAL HOSPITAL Kong, Jian Boston, MA 2019
NOFO Title: Behavioral & Integrative Treatment Development Program (R34 Clinical Trial Optional)
NOFO Number: PA-18-073
Summary:

Low back pain (LBP) is one of the most common reasons for all physician visits in the U.S. The financial costs associated with the care of LBP are staggering. The treatments for chronic low back pain (cLBP) are far from satisfactory, and opioids are often prescribed with varying degrees of success. This study builds on prior work suggesting that auricular transcutaneous vagus nerve stimulation (tVNS), a non-invasive therapeutic, can significantly reduce symptoms of chronic pain and common comorbidities of chronic pain, such as depression and anxiety. This proposal aims to investigate the treatment effect and underlying mechanism of tVNS on chronic low back pain. Patients with chronic low back pain will be randomized to either real or sham tVNS treatment for 1 month, with a 3-month follow-up. This study, if successful, could provide new treatment options for chronic low back pain and reduce the use of opioid analgesics in chronic pain management.
1UG3DA050306-01
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.
1R01DA047574-01
In vivo characterization of opioid biased agonists Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA MCLEAN HOSPITAL Paronis, Carol A; Bergman, Jack Belmont, MA 2019
NOFO Title: Prescription Drug Abuse (R01 Clinical Trial Optional)
NOFO Number: PA-18-058
Summary:

The ongoing opioid crisis has led to renewed concerns about the clinical prescription of addictive opioid analgesics. However, there are currently no suitable alternatives for treating severe or malignant pain. Studies of opioid signaling mechanisms in mice deficient in ?-arrestin have suggested that biased agonists displaying preferential activation of G-protein signaling over ?-arrestin signaling could offer a promising avenue for the development of opioid analgesics with a reduced adverse effects profile. However, there is no concluding evidence showing that such biased signaling can indeed be associated with reduced opioid side effects and, consequently, an improved safety profile. This research will address the need for preclinical data to rigorously evaluate this hypothesis with a program of in vivo studies to compare the effects of “balanced” opioids (morphine, oxycodone, and fentanyl) with that of the “biased” agonists PZM21 and two novel ligands provided by colleagues at the NIDA IRP in nonhuman primates. The results of these studies will provide critical information regarding the dependence liability of “biased” agonists that, in clinical practice, might be given on a repeated, or chronic, basis, potentially adding a powerful new tool for the safer management of severe or malignant pain.
1R01DA045695-01A1
Treating Chronic Pain in Buprenorphine Patients in Primary Care Settings Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA BOSTON UNIVERSITY MEDICAL CAMPUS Stein, Michael D; Weisberg, Risa B Boston, MA 2019
NOFO Title: Behavioral & Integrative Treatment Development Program (R01 Clinical Trial Optional)
NOFO Number: PA-18-055
Summary:

Often (around 40 percent of the time), individuals being treated for opioid use disorder (OUD) also have pain that interferes with daily life. This study builds on the prior development of a collaborative primary care approach, entitled TOPPS (Treating Opioid Patients’ Pain and Sadness), in which behavioral health specialists and primary care providers share a unified plan for addressing pain and depression in patients receiving buprenorphine. Building in preliminary work, researchers are conducting a randomized controlled trial of TOPPS compared to a health education contact-control condition among 250 persons with OUD recruited from two primary care-based buprenorphine programs, provided over 3 months and followed over 12 months. The study will examine whether this intervention changes how much pain interferes with daily functioning, the severity of pain, depression, and whether individuals stay in OUD treatment.