VK4-116 for Opioid Use Disorder

Overseen By Debra Kelsh, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: Opioids, Benzodiazepines, others

Disqualifiers: Cardiac, Hepatic, Renal, Neurologic, others

Compensation: Varies

Number of Visits: 2

Duration: 4 days for fasted condition, 8 days for fed condition

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called VK4-116, developed for people with opioid use disorder. The main goal is to assess the treatment's safety, tolerability, and how the body processes it. Participants will receive different doses to compare effects, either with or without food, or a placebo (a harmless pill with no active drug). The trial seeks healthy individuals without significant medical conditions who do not use nicotine products. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking prescribed medications 14 days before the study and over-the-counter medications, supplements, or vitamins 7 days before the study.

Is there any evidence suggesting that VK4-116 is likely to be safe for humans?

Research has shown that VK4-116 demonstrates promising safety results in lab studies. These studies suggest that VK4-116 is safe in lab settings, which bodes well for its development as a treatment for opioid use disorder. However, since this clinical trial is in its earliest phase, it primarily focuses on assessing the safety of VK4-116 in humans. The trial aims to determine how well people tolerate the treatment and identify any side effects. Until the trial progresses, direct information on VK4-116's effects on people remains limited. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Researchers are excited about VK4-116 for opioid use disorder because it offers a new approach compared to existing treatments like methadone or buprenorphine, which primarily work by acting on opioid receptors. VK4-116 is unique because it targets different pathways in the brain, potentially reducing cravings and withdrawal symptoms without relying on opioid receptor activity. This novel mechanism might provide an alternative for those who do not respond well to current medications. Additionally, VK4-116 is administered orally, which could make it a convenient option for patients.

What evidence suggests that VK4-116 might be an effective treatment for opioid use disorder?

Research has shown that VK4-116, a drug tested in this trial for opioid use disorder (OUD), can be effective. It blocks a specific brain receptor linked to addiction. Studies have found that VK4-116 reduced opioid use and eased withdrawal symptoms. It also improved behaviors like decision-making, often affected by drug use. Although most of this information comes from lab studies, these early results are promising for VK4-116 as a potential treatment for OUD. ^{2 4 6 7 8}

Who Is on the Research Team?

Marta De Santis, PhD

Principal Investigator

National Institute on Drug Abuse, NIH

Are You a Good Fit for This Trial?

This trial is for healthy volunteers who want to help test a new drug called VK4-116. It's not for people with opioid use disorder or addiction, but the results might one day help those who do.

Inclusion Criteria

I am following the required birth control guidelines.

Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures

Be able and willing to comply with protocol requirements and the rules and regulations of the study site, and be likely to complete all the study treatments

Exclusion Criteria

Use nicotine products via smoking/vaping in past 6 months

I have a history of heart conditions.

Have any clinically significant finding within one year of Screening that contraindicates participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive a single ascending dose of VK4-116 or placebo and are monitored for safety, tolerability, and pharmacokinetics

4 days for fasted condition, 8 days for fed condition

Continuous monitoring during clinic stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• VK4-116

Trial Overview VK4-116 is being tested in this study. Volunteers will take different doses of the drug or a placebo without knowing which they're getting. The study looks at how safe it is and how the body processes it when taken with and without food.

How Is the Trial Designed?

Group I: 500 mg dose Experimental Treatment 1 Intervention

oral administration in fasted state

Group II: 50 mg dose Experimental Treatment 1 Intervention

oral administration in fasted state

Group III: 400 mg dose Experimental Treatment 1 Intervention

oral administration in fasted state

Group IV: 200 mg dose in fed state Experimental Treatment 1 Intervention

oral administration in fed state

Group V: 200 mg dose Experimental Treatment 1 Intervention

oral administration in fasted state

Group VI: 100 mg dose Experimental Treatment 1 Intervention

oral administration in fasted state

Group VII: placebo Placebo Group 2 Interventions

oral administration

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Altasciences Company Inc.

Industry Sponsor

Trials

18

Recruited

860+

Published Research Related to This Trial

Medications like methadone, buprenorphine, and extended-release naltrexone are effective in improving outcomes for individuals with opioid use disorder, but their effectiveness is often hindered by challenges in diagnosis, treatment entry, and retention.

There is a critical need to enhance the use of these medications through better training for healthcare professionals and the development of new treatment models to provide personalized care for those affected by opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of opioid use disorder in the USA: present status and future directions. Blanco, C., Volkow, ND.[2019]

Over 2 million Americans have opioid use disorder, which is partly due to overprescribing, highlighting the need for better opioid stewardship and management strategies by physicians.

Three FDA-approved medications—methadone, buprenorphine, and naltrexone—are effective for treating opioid use disorder, but successful outcomes are best achieved through comprehensive, interprofessional management plans rather than relying solely on medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Drug and Alcohol Use Disorders: Opioid Use Disorder. Witt, L., Butler, F.[2019]

Citations

1. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0315569

In vitro safety evaluation of dopamine D3R antagonist, R-VK4 ... These results demonstrated that R-VK4-116 possesses favorable in vitro safety properties and supports further development as a potential medication for OUD.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10508727/

The selective D3-Receptor antagonist VK4-116 effectively ... In the present study, we found that pretreatment with a selective D3R antagonist (VK4-116) restored cocaine use-induced deficit in behavioral inference and ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524268373

Newly Developed Dopamine D3 Receptor Antagonists, R- ... Similarly, R-VK4-116 alone dose-dependently reduced cocaine-induced increases in blood pressure and heart rate. These results highlight the safety of new D3R ...

4. frontiersin.org frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2019.00292/full

Dopamine D 3 Receptor Antagonism Reverses ... In summary, the present study found that VK4-116 decreased opioid self-administration and attenuated aversive states that were induced by ...

5. nature.com nature.com/articles/s41386-024-01858-7

The selective D3Receptor antagonist VK4-116 reverses ... In the present study, we found that pretreatment with a selective D3R antagonist (VK4-116) reversed the cocaine-induced deficit in inference in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06808932

NCT06808932 | VK4-116 Phase I Study With Food-Effect This first-in-human, randomized, double-blind, placebo-controlled, single ascending dose (SAD), phase I study is designed to assess the safety, tolerability and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11649115/

In vitro safety evaluation of dopamine D3R antagonist, R-VK4 ... These results demonstrated that R-VK4-116 possesses favorable in vitro safety properties and supports further development as a potential medication for OUD.

8. sophion.com sophion.com/publication/in-vitro-safety-evaluation-of-dopamine-d-3-r-antagonist-r-vk4-116-as-a-potential-medication-for-the-treatment-of-opioid-use-disorder/

In vitro safety evaluation of dopamine D 3 R antagonist , R R-VK4-116 is currently being developed as a medication to treat opioid use disorder (OUD). To characterize in vitro safety properties of R-VK4-116, ...