Funded Projects

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.

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.

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:

This study will conduct preclinical and clinical assessments of the NMDA modulator NYX-783 for treatment of opioid drug-seeking and relapse to opioid use disorder (OUD). NYX-783, a novel small molecule being developed by Aptinyx, has shown evidence of safety/tolerability in Phase 1 studies and is currently in Phase 2 trials for post-traumatic stress disorder. This project will test the safety, tolerability, and pharmacokinetics (PK) of NYX-718 in morphine-maintained patients in residential settings and then conduct a combined inpatient (safety/tolerability/PK) / outpatient (preliminary efficacy) study testing NYX-783’s effects on opioid use and relapse, stress/cue reactivity, craving, and quality of life in OUD subjects maintained on standard extended release naltrexone over a 10-week period. Successful completion of these studies will set the stage for larger scale Phase 2/3 studies of efficacy in OUD that will ultimately be required for FDA approval of NYX-783 for the treatment of drug-seeking and relapse in OUD.

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.

NOFO Title: Behavioral & Integrative Treatment Development Program (R34)
NOFO Number: PA-16-073
Summary:

The increased risk of maternal, obstetric, and newborn morbidity and mortality associated with perinatal prescription opioid (PO) misuse and opioid use disorder (OUD) is well established. Despite clear advances in maternal, fetal, and newborn health with treatment of perinatal opioid misuse and OUD, much work remains. Preliminary data has demonstrated significant reductions in opioid misuse as a result of our Cognitive Behavioral Therapy (CBT) program for pain combined with shared decision making for medication management for pregnant women misusing POs or with OUD (including heroin). However, access to the program is still limited and several obstacles to its expansion remain. This proposal will fill this critical gap by converting their CBT intervention from in-person sessions to a web-based interface. The proposed research will result in a critical advance in the management of opioid use and abuse during pregnancy and prevent both the acute and long-term risks associated with pre- and perinatal PO misuse and OUD, including overdose and death.

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.

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:

A recent FDA public meeting identified sleep disturbance as a primary contributor to opioid use disorder (OUD) treatment failure. Suvorexant (SUVO; Belsomra®) is a dual orexin receptor antagonist that is FDA-approved for insomnia, with low addiction liability, that improves sleep continuity with a single dose, has an extremely safe and mild side-effect profile, has clear interactions with the opioid system, and has not yet been evaluated in OUD patients. The hypothesis is that SUVO will improve total sleep time during withdrawal, have no addiction liability, and be more efficacious than trazodone, a common OUD-associated insomnia medication. Primary outcomes will be objective sleep measures and addiction liability. Secondary measures will include objective, biological, and self-report measures of opioid withdrawal severity, treatment retention, craving, and stress. Results will advance the treatment of OUD, the understanding of sleep and opioids, and the use of SUVO in clinical populations.

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:

Responding to urgent calls for non-opioid treatment, this research group has been evaluating the therapeutic potential of cannabidiol (CBD), a non-intoxicating cannabinoid, for the treatment of some clinical aspects of opioid use disorder (OUD). Preclinical animal studies show that CBD decreases cue-induced heroin-seeking behavior during drug abstinence, associated with incubation of craving. Clinical work has also shown that CBD was safe in combination with a potent opioid agonist to address a potential relapse condition and decreased craving and anxiety associated with heroin cues in abstinent individuals with heroin use disorder. Building on this foundation, the researchers will investigate an oral CBD powered by a novel patented technology (leveraging the kinetics of long-chain fatty acid absorption) in a gelcap delivery system that improves bioavailability, reduces the incidence of gastrointestinal side effects, reduces first pass metabolism, and enhances onset time. This study could lead to the development of a non-opioid, non-intoxicating FDA-approved medication to reduce opioid craving and relapse and restore global functioning in individuals with OUD.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: DA19-002

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.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: DA19-002

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 adverse effects of morphine and other mu-opioid receptor (MOR) agonists are linked to the ?-arrestin pathway, while analgesia is tied to the G-protein pathway. Pathway specific or “biased” drug development can target G-protein specific agonists that avoid the negative consequences of ?-arrestin signaling activation and produce analgesia. Highly “biased” MOR agonists have promise as effective analgesics but devoid of opioid-induced adverse effects. Preclinical studies compared two compounds, MEB-1166 and MEB-1170, against Oliceridine and morphine. Both compounds displayed no respiratory depression, even at high doses, while morphine and Oliceridine significantly reduced respiratory function. In contrast to morphine, neither MEB-1166 nor MEB-1170 produced conditioned place preference, suggesting an absence of abuse liability. This study will characterize the pharmaceutical and pharmacological profiles and perform liability studies for these compounds.

NOFO Title: Device-Based Treatments for Substance Use Disorders (UG3/UH3, Clinical Trial Optional)
NOFO Number: PAR-18-494