Tezampanel for Drug Withdrawal

Overseen By Christopher Toombs

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Proniras Corporation

Must be taking: Methadone, Buprenorphine

Must not be taking: Benzodiazepines, Barbiturates, Dopamine stimulants

Disqualifiers: Active psychosis, Alcohol use disorder, Seizure disorder, Cardiac abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 week

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Tezampanel, a new treatment for individuals experiencing opioid withdrawal symptoms. The goal is to determine if Tezampanel is safe and effective in easing these symptoms during a week-long stay at a research center. Participants will receive either the actual drug or a placebo (a substance with no therapeutic effect) to compare results. Individuals who have been using opioids and are currently in a treatment program for opioid addiction might be suitable for this study. 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.

Do I need to stop my current medications to join the trial?

The trial does not specify that you need to stop taking your current medications. However, certain medications, especially those affecting the dopamine system or used for addiction, ADHD, insomnia, or bipolar disorders, are not allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that Tezampanel is likely to be safe for humans?

Research shows that Tezampanel is under investigation as a potential treatment for opioid withdrawal symptoms. While specific information about its safety in humans for this use is limited, its testing in early human trials indicates some initial safety in earlier studies. This suggests a likely low risk of serious side effects. However, this early phase study primarily focuses on assessing safety and understanding the drug's metabolism. Participation in this trial will help researchers learn more about Tezampanel's tolerability for treating opioid withdrawal. ^{1 2 3 4 5}

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

Most treatments for drug withdrawal rely on medications that alleviate symptoms or substitute the drug being withdrawn. Tezampanel stands out because it targets the AMPA and kainate receptors, offering a novel approach to managing withdrawal symptoms. This mechanism is different from the typical treatments that primarily focus on opioid receptors. Researchers are excited about tezampanel because it could provide a new pathway to ease withdrawal symptoms, potentially enhancing recovery rates with fewer side effects.

What evidence suggests that Tezampanel might be an effective treatment for Opioid Withdrawal Syndrome?

Research has shown that Tezampanel (TZP) might help reduce symptoms of opioid withdrawal by blocking certain brain signals involved in withdrawal. Early results suggest that Tezampanel can ease these symptoms, making it easier for people to stop using opioids. In this trial, participants will divide into different cohorts to receive varying doses of Tezampanel, with initial participants in each cohort receiving a placebo. Although more studies are needed, current evidence is promising for those dealing with opioid use disorder. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Opioid Use Disorder who've recently used opioids. They must be willing to stay inpatient for a week, have stable mental health medication if needed, and agree to birth control or are post-menopausal/sterile. Those on opioid maintenance treatment may join but can't be seeking other specific treatments.

Inclusion Criteria

I have read and understand the information about the trial and agree to participate.

My current medications have not changed recently.

I currently use opioids or am on treatments like buprenorphine or methadone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tezampanel or placebo daily during a 7-day inpatient stay to assess safety, pharmacokinetics, and efficacy for opioid withdrawal syndrome

1 week

Daily visits (inpatient)

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

• Tezampanel

Trial Overview The study tests Tezampanel (TZP) against a placebo to see if it helps with Opioid Withdrawal Syndrome during a 7-day hospital stay. Participants will get TZP or placebo daily from Day 2 to Day 7 while their safety and the drug's effects are monitored.

How Is the Trial Designed?

Group I: Cohort D Experimental Treatment 2 Interventions

10 participants will be recruited. The first two participants will receive placebo followed by eight participants who will receive active drug (tezampanel) at the next highest dose level.

Group II: Cohort C Experimental Treatment 2 Interventions

10 participants will be recruited. The first two participants will receive placebo followed by eight participants who will receive active drug (tezampanel) at the next highest dose level.

Group III: Cohort B Experimental Treatment 2 Interventions

10 participants will be recruited. The first two participants will receive placebo followed by eight participants who will receive active drug (tezampanel) at the next highest dose level.

Group IV: Cohort A Experimental Treatment 2 Interventions

10 participants will be recruited. The first two participants will receive placebo followed by eight participants who will receive active drug (tezampanel) at the lowest dose level.

Who Is Running the Clinical Trial?

Proniras Corporation

Lead Sponsor

Trials

1

Recruited

40+

Indiana University School of Medicine

Collaborator

Trials

194

Recruited

181,000+

Published Research Related to This Trial

Aprepitant, an oral medication that blocks neurokinin-1 receptors, is effective in preventing chemotherapy-induced nausea and vomiting, especially when used alongside other antiemetics like dexamethasone and 5-HT3 receptor antagonists.

In pivotal phase III trials with 1099 patients, aprepitant improved complete control of emesis by 20% compared to standard therapy, particularly in preventing delayed nausea and vomiting, demonstrating its efficacy across different patient demographics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aprepitant in antiemetic combinations to prevent chemotherapy-induced nausea and vomiting. Olver, IN.[2019]

In a study of 225 patients undergoing chemotherapy for malignant lymphomas, adding alprazolam to granisetron did not significantly improve the rates of complete response to emesis compared to granisetron alone, with response rates being high in both groups (G: 83-94% vs G+A: 89-97%).

However, patients receiving alprazolam experienced significantly more somnolence, indicating a potential safety concern with its use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granisetron plus or minus alprazolam for emesis prevention in chemotherapy of lymphomas: a randomized multicenter trial. Granisetron Trialists Group. Bauduer, F., Coiffier, B., Desablens, B.[2019]

The combination of NEPA (netupitant and palonosetron) has been shown to be superior to palonosetron alone in controlling chemotherapy-induced nausea (CIN) after highly emetogenic chemotherapy, maintaining efficacy over multiple treatment cycles.

Recent studies suggest that olanzapine may offer superior efficacy in preventing nausea compared to NK1 receptor antagonists (NK1RAs) like rolapitant, indicating a potential shift in preferred antiemetic strategies for patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists. Bošnjak, SM., Gralla, RJ., Schwartzberg, L.[2022]

Oral rolapitant (180 mg) is effective in preventing delayed chemotherapy-induced nausea and vomiting (CINV) in adults undergoing highly or moderately emetogenic chemotherapy, showing benefits over multiple cycles of treatment.

Rolapitant has a similar tolerability profile to placebo and does not interact with CYP3A4, which means it does not require dose adjustments for dexamethasone, making it a safer option for patients on other medications that are metabolized by this enzyme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rolapitant: A Review in Chemotherapy-Induced Nausea and Vomiting. Heo, YA., Deeks, ED.[2019]

All neurokinin 1 (NK1) receptor antagonists (RAs) are effective in preventing chemotherapy-induced nausea and vomiting (CINV), with greater benefits observed in delayed CINV when using three-drug regimens compared to two-drug regimens.

While NK1 RAs are generally well tolerated, there are safety concerns, such as hypersensitivity reactions associated with IV rolapitant and infusion-site reactions with IV fosaprepitant, highlighting the need for careful monitoring and consideration of potential drug-drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. Navari, RM., Schwartzberg, LS.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06538558

Study to Assess the Use of Tezampanel for Opioid ... This study is examining the use of Tezampanel (TZP) for treatment of Opioid Withdrawal Syndrome (OWS) in participants with Opioid Use Disorder (OUD).

2. proniras.com proniras.com/wp-content/uploads/2024/11/Proniras-Clinical-Trial-Release-11-14-24.pdf

Clinical Trial Release (11-14-24) The results may show that PRN-001-01 (tezampanel) can relieve patients from withdrawal symptoms, potentially alleviating a crucial impediment in ...

3. proniras.com proniras.com/clinical-trial/

Clinical Trial Results of this trial may demonstrate that tezampanel liberates treatment seeking patients from the unwanted torment of withdrawal, thereby enabling a sorely ...

4. acceleratorlsp.com acceleratorlsp.com/category/press-releases/

Press Releases PRN-001-01 (tezampanel) is a novel antagonist of glutaminergic signaling with potential to suppress opiate withdrawal symptoms

5. firstwordpharma.com firstwordpharma.com/story/5108705

Proniras Corporation Announces National Institute on Drug ... "The tezampanel data generated to date suggest that this proprietary glutamate receptor antagonist may have significant clinical utility in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06538558?term=AREA%5BInterventionSearch%5D(LY293558)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=2

Study to Assess the Use of Tezampanel for Opioid Withdrawal ... Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

7. acceleratorlsp.com acceleratorlsp.com/proniras-corporation-announces-first-patient-enrolled-in-phase-1-clinical-trial-for-opioid-withdrawal-syndrome/

Proniras Corporation Announces First Patient Enrolled in ... The results may show that PRN-001-01 (tezampanel) can relieve patients from withdrawal symptoms, potentially alleviating a crucial impediment ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6847983/

AMPA Receptor Positive Allosteric Modulators Attenuate ... Also, aniracetam at a dose of 100 mg/kg (i.p.) significantly decreased the withdraw jumps precipitated by naloxone (21.1 ± 7.6, p<0.001 v.s. morphine alone, Fig ...