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

Trial Summary

What is the purpose of this trial?

This study is examining the use of Tezampanel (TZP) for treatment of Opioid Withdrawal Syndrome (OWS) in participants with Opioid Use Disorder (OUD). Participants will receive TZP or placebo (PBO) daily on Days 2 - 7 during a 7-day inpatient stay at the research center to determine safety, pharmacokinetic (PK) assessment, and efficacy of TZP for OWS.

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.

How is the drug Tezampanel unique for treating drug withdrawal?

Tezampanel is unique because it is an AMPA/kainate receptor antagonist, which means it works by blocking specific receptors in the brain that are involved in excitatory neurotransmission. This mechanism is different from other treatments for drug withdrawal, which often focus on replacing the drug or managing symptoms rather than directly modulating neurotransmitter systems. ^{1 2 3 4 5}

Eligibility Criteria

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

My current medications have not changed recently.

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

I have been diagnosed with Opioid Use Disorder.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. India pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Granisetron plus or minus alprazolam for emesis prevention in chemotherapy of lymphomas: a randomized multicenter trial. Granisetron Trialists Group. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Rolapitant: A Review in Chemotherapy-Induced Nausea and Vomiting. [2019]