TRV734 for Opioid Use Disorder

Overseen By NIDA IRP Screening Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute on Drug Abuse (NIDA)

Must be taking: Methadone

Must not be taking: Antidepressants, Antipsychotics, Benzodiazepines, others

Disqualifiers: Psychotic disorder, Bipolar, Major depression, Alcohol dependence, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new drug, TRV734, can help individuals with opioid use disorder (OUD) manage withdrawal symptoms with fewer side effects than oxycodone. It seeks to offer an alternative to methadone, which is commonly used but can have significant side effects. Participants will take TRV734, oxycodone, or a placebo to compare their effects. This study may suit those who have been on daily methadone treatment for OUD for at least three months and can tolerate missing a couple of doses without severe withdrawal symptoms. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must continue your regular methadone treatment. However, you should not take medications that could alter the effects of the study drugs, like strong CYP3A4 inhibitors or inducers, or medications that could affect opioid withdrawal symptoms.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that TRV734 has undergone testing in people and was generally safe and well-tolerated. This drug resembles methadone but may cause fewer side effects. Although TRV734 remains under study, earlier research demonstrated its safety for humans. Prospective trial participants might find this information reassuring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for opioid use disorder, like methadone and buprenorphine, work by partially activating opioid receptors to reduce cravings and withdrawal symptoms. However, TRV734 is unique because it selectively targets the mu-opioid receptor with a biased activation approach. This means it aims to provide effective withdrawal suppression while potentially minimizing the side effects commonly associated with traditional opioids, such as respiratory depression. Researchers are excited about TRV734 because this novel mechanism could offer a safer alternative for managing opioid withdrawal, addressing a critical need in addiction treatment.

What evidence suggests that TRV734 might be an effective treatment for opioid use disorder?

Research shows that TRV734, which participants in this trial may receive, targets the mu receptor to help ease withdrawal symptoms and drug cravings in people with opioid use disorder (OUD), similar to methadone. Studies suggest that TRV734 may cause fewer side effects than traditional treatments like oxycodone. Early results indicate that TRV734 is generally safe when taken orally. This new drug could offer a promising option for managing withdrawal symptoms in OUD patients who need more treatment choices. ^{1 2 3 4 6}

Who Is on the Research Team?

David H Epstein, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

Adults aged 18-75 with opioid use disorder, on methadone treatment for at least 3 months, willing to skip doses and provide blood samples. Women must not be pregnant or breastfeeding and agree to contraception; men must practice abstinence or use barrier contraception.

Inclusion Criteria

Participants must be able to speak, read, and understand English. Justification: This study uses scales and experimental procedures that are validated only in English. This includes the assessments conducted to test the primary and secondary outcomes and is therefore required to maintain the research integrity of the study.

You have experienced strong withdrawal symptoms after missing a day or two of taking methadone. We will use a special questionnaire to ask you about your withdrawal history for this study.

I am willing to give blood samples through an IV in my arm.

Exclusion Criteria

I do not have any serious health issues that would make research participation unsafe.

I have been diagnosed with severe depression that is not currently under control.

I was unable to pass the consent understanding test for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pilot Phase

Participants in an unpowered dose-finding five-session pilot phase will receive placebo, oxycodone, and a range of doses of TRV734.

30 days

Inpatient stay

Main Treatment Phase

Participants will stay at the inpatient unit for up to 21 consecutive days to test TRV734 at different doses vs. oxycodone and placebo for withdrawal suppression.

21 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TRV734

Trial Overview The trial is testing TRV734's effectiveness in relieving withdrawal symptoms compared to oxycodone, without as many side effects. Participants will stay in a unit for up to three weeks, receive their regular methadone dose, occasionally skip it for testing purposes, and take either the study drug, placebo or oxycodone.

How Is the Trial Designed?

Group I: TRV734 Experimental Treatment 1 Intervention

TRV734 at different doses vs. oxycodone for withdrawal suppression

Group II: Placebo Placebo Group 1 Intervention

Placebo capsule

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04316559

Study Details | NCT04316559 | Biased Opioid Agonists for ... A new drug, TRV734, could be used like methadone to treat OUD. It might not have as many side effects. Objective: To test if TRV734 relieves withdrawal symptoms ...

2. trevena.com trevena.com/pipeline/trv734

TRV734 Both target the mu receptor and can successfully alleviate withdrawal symptoms and drug cravings.

3. withpower.com withpower.com/trial/phase-3-9-2021-ccd72

TRV734 for Opioid Use Disorder · Info for Participants TRV734. Trial Overview The trial is testing TRV734's effectiveness in relieving withdrawal symptoms compared to oxycodone, without as many side effects.

4. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.721

A First‐in‐Human Clinical Study With TRV734, an Orally ... In conclusion, this first-in-human study of TRV734 showed that this novel, orally administered μ-opioid receptor agonist was generally safe and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10299742/

Improving Translational Research Outcomes for Opioid Use ... Pharmacotherapies are the most effective means of reducing the harms associated with opioid use disorder (OUD). Translational research seeking to develop ...

6. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=20-DA-N014&&query=

Protocol Details A new drug, TRV734, could be used like methadone to treat OUD. It might not have as many side effects. Objective: