Study to Assess the Use of Tezampanel for Opioid Withdrawal Syndrome in Treatment-Seeking Patients With Opioid Use Disorder

NCT06538558 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TZP-OWS-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Opioid Use Disorder

Keywords

opioid; OUD; opioid withdrawal syndrome

Outcome Measures

Primary Outcomes (1)

• To evaluate systemic tolerability and safety of intravenous tezampanel administration.

  Monitoring incidence of dose-limiting toxicities, incidence and severity of treatment emergent adverse events.

  First Dose through Day 10 visit

Secondary Outcomes (2)

• To characterize Cmax (maximum concentration) of tezampanel

  Day 2 and Day 5 (multiple pre and post dose timepoints)

• To characterize Area Under the Curve (AUC) concentration of tezampanel

  Day 2 and Day 5 (multiple pre and post dose timepoints)

Study Arms (4)

Cohort A

EXPERIMENTAL

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.

Drug: Tezampanel; Drug: Placebo

Cohort B

EXPERIMENTAL

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.

Drug: Tezampanel; Drug: Placebo

Cohort C

EXPERIMENTAL

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.

Drug: Tezampanel; Drug: Placebo

Cohort D

EXPERIMENTAL

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.

Drug: Tezampanel; Drug: Placebo

Interventions

Tezampanel DRUG

Study drug will be given intravenously (mg/kg) at 6 timepoints during study participation

Also known as: TZP

Cohort A; Cohort B; Cohort C; Cohort D

Placebo DRUG

Placebo will be given intravenously (mg/kg) at 6 timepoints during study participation to a subset of participants in each cohort.

Also known as: PBO

Cohort A; Cohort B; Cohort C; Cohort D

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, female or non-binary, age 18 to 65 years of age at Screening.
• Diagnosis of Opioid Use Disorder (OUD)
• Positive Urine Drug Screen (UDS) for opioid(s) at the Screening and Baseline Visits.
• Recent active/chronic use of short-acting illicit and/or prescribed opioids and/or long-acting Opioid Use Disorder (OUD) maintenance treatments buprenorphine or methadone at the Screening and Baseline Visits.
• Already engaged and fully assessed in a longitudinal-outpatient treatment program that provides opioid addiction treatment encompassing the full spectrum of opioid maintenance and abstinence (injectable Vivitrol®) treatments, in which the host clinic is prepared and equipped to continue with:
• maintenance treatment (methadone or buprenorphine treatment) for study non-completers, or
• long-acting injectable naltrexone treatment (Vivitrol®), for completers with next dose delivered approximately 30 days after Study Day 6.
• Post-menopausal/sterile or agree to use chemical or barrier methods of birth control from time of informed consent through 30 days post last treatment.
• Stable concomitant medications.
• Stable concomitant medications for depression, post-traumatic stress disorder, psychotic disorders, and bipolar spectrum disorders if one of the following: SSRI, SNRI, bupropion, MAOI, trazodone, Tricyclic, typical and atypical antipsychotics, lithium, antihistamine, alpha-adrenergic agent, nicotine replacement.
• Stable concomitant medications: propranolol, prazosin, and clonidine if used for psychiatric reasons, and not to control hypertension at the Baseline Visit and unchanged on Study Day 1.
• Provide informed consent.
• Understand and follow Lifestyle Considerations per protocol.

You may not qualify if:

• Clinically at risk or unstable due to:
• Active psychosis or mania that is impairing insight, decision-making, perception, or ability to provide informed consent as assessed by the PI or designee during the Screening or Baseline Visits, discussion with the outpatient treatment provider, or at Study Day 1.
• Active suicidal ideation or intent as assessed by the PI or designee during the Baseline Visit interview or the C-SSRS on Study Day 1.
• Chronic benzodiazepine use, or at significant risk for, or in a state of benzodiazepine withdrawal at the Screening or Baseline Visits, Study Day 1, or in discussion with the outpatient treatment provider.
• Alcohol Use Disorder as assessed by the PI or designee with \> 14 drinks / week (average of \> 2 / day) at the Screening or Baseline Visits or Study Day 1 or in discussion with the outpatient treatment provider.
• Seizure disorder; use of anti-convulsant for bipolar disorder, seizure, or chronic pain (including topiramate, gabapentin, carbamazepine, valproic acid) at the Screening or Baseline Visits or Study Day 1.
• Cardiac abnormalities including arrythmia, conduction abnormality or baseline QTC prolongation (QTcF \> 450 males; 470 females); pacemaker, history of myocardial infarction at the Baseline Visit.
• Hypertension, diabetes mellitus, cancer, liver, and/or kidney disease and associated medications at the Screening or Baseline Visits or at Study Day 1.
• Abnormal safety laboratory results.
• ALT or AST \> 3xs upper limit of normal at Baseline or Study Day 1.
• Undiagnosed hypertension defined as:
• Baseline Visit: BP \> 160 / 100 mmHg or heart rate \> 120 bpm
• Study Day 1: BP ≥ 180 / 120 mmHg or heart rate ≥ 140 bpm that continues after 10 minutes of rest.
• Temperature \> 38.1°C at the Baseline Visit. Temperature \> 38.9°C at the Study Day 1.
• Medications that stimulate the dopamine system pre- or post-synaptically, including L-Dopa, lisdexamfetamine, modafinil, gabapentin, phenobarbital, etc.) at the Screening or Baseline Visits or Study Day 1.

Sponsors & Collaborators

• Proniras Corporation: lead
• Indiana University School of Medicine: collaborator

Study Sites (1)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

tezampanel

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Central Study Contacts

Christopher Toombs

CONTACT

206-957-7321; ctoombs@proniras.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant remains blinded. Investigator and study sponsor are unblinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be divided into four dose escalation cohorts. A DSMB safety review will be completed after each cohort (at a minimum) to determine appropriateness of continuing dose escalation.

Study Record Dates

• First Submitted: July 31, 2024
• First Posted: August 5, 2024
• Study Start: October 16, 2024
• Primary Completion: October 14, 2025
• Study Completion: November 30, 2025
• Last Updated: November 6, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)