Tezampanel for Drug Withdrawal
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
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.
12345Eligibility 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 am between 18 and 65 years old.
+7 more
Trial 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)
Participant Groups
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.
4Treatment groups
Experimental Treatment
Group I: Cohort DExperimental Treatment2 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 CExperimental Treatment2 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 BExperimental Treatment2 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 AExperimental Treatment2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Indiana University School of MedicineIndianapolis, IN
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Who Is Running the Clinical Trial?
Proniras CorporationLead Sponsor
Indiana University School of MedicineCollaborator
References
Aprepitant in antiemetic combinations to prevent chemotherapy-induced nausea and vomiting. [2019]Aprepitant is an oral neurokinin-1 receptor antagonist which acts centrally to block chemotherapy-induced emesis. Its main pathway of elimination is by the cytochrome p450 isozyme CYP3A4, which is the basis for drug interactions with dexamethasone and oral contraceptives. Aprepitant is well tolerated, and phase II trials in high-dose cisplatin-induced emesis showed that it is most effective when 125 mg orally is added to a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone for acute emesis and then an 80 mg oral dose continued with dexamethasone on days 2 and 3 to prevent delayed emesis. Two pivotal phase III trials enrolling a total of 1099 patients showed that the complete control of emesis improved by 20% in patients receiving aprepitant as compared with standard therapy, with the most impressive differences being in delayed emesis. Control was maintained over multiple cycles and occurred in both males and females and young and old adults.
Granisetron plus or minus alprazolam for emesis prevention in chemotherapy of lymphomas: a randomized multicenter trial. Granisetron Trialists Group. [2019]Anxiety can increase the risk of chemotherapy related emesis. We have studied the role of a benzodiazepine (alprazolam: A) in addition to granisetron for controlling emesis in patients treated with moderately emetogenic chemotherapy for malignant lymphomas according to an anxiety scale (Covi score). Two hundred twenty-five patients receiving at least 3 cycles of chemotherapy including adriamycin and/or cyclophosphamide and/or epirubicin and/or dacarbazine were randomized. Patients in arm G (n = 111) received 3 mg i.v. granisetron 10 min before chemotherapy at cycles (C) 1, 2 and 3 while in arm G+A (n = 114), alprazolam (A) was added per os 1 mg 1 hour before chemotherapy (H-1) and 0.5 mg at H+6 for C1. At C2 and C3, A was given 0.75 or 1.5 mg at H-48, H-24, H-1 and 0.5 mg at H+6. Patients characteristics were comparable between the 2 arms. Complete response rates (i.e. no emesis or at least slight nausea) were similar in both arms: G: 83, 94 and 93% versus G+A: 89, 93 and 97% in C1, C2 and C3 respectively. Nevertheless, the Covi score of the population was low rendering difficult the study of the factor "anxiety". Somnolence was significantly more frequent in the G+A arm (p
Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. [2020]To examine pharmacologic and clinical characteristics of neurokinin 1 (NK1)-receptor antagonists (RAs) for preventing chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy, a literature search was performed for clinical studies in patients at risk of CINV with any approved NK1 RAs in the title or abstract: aprepitant (capsules or oral suspension), HTX019 (intravenous [IV] aprepitant), fosaprepitant (IV aprepitant prodrug), rolapitant (tablets or IV), and fixed-dose tablets combining netupitant or fosnetupi-tant (IV netupitant prodrug) with the 5-hydroxytryptamine type 3 (5HT3) RA palonosetron (oral or IV). All NK1 RAs are effective, but exhibit important differences in efficacy against acute and delayed CINV. The magnitude of benefit of NK1-RA-containing three-drug vs two-drug regimens is greater for delayed vs acute CINV. Oral rolapitant has the longest half-life of available NK1 RAs, but as a consequence should not be administered more frequently than every 2 weeks. In general, NK1 RAs are well tolerated; however, IV rolapitant was recently removed from US distribution, due to hypersensitivity and anaphylaxis, and IV fosaprepitant is associated with infusion-site reactions and hypersensitivity presumed related to its polysorbate 80 excipient. Also, available NK1 RAs have potential drug-drug interactions. Adding an NK1 RA to 5HT3 RA and dexamethasone significantly improves CINV control vs the two-drug regimen. Newer NK1 RAs offer more formulation options, higher acute-phase plasma levels, or improved tolerability, and increase clinicians' opportunities to maximize benefits of this important class of antiemetics.
Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists. [2022]Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK1RAs when combined with 5-HT3RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone-metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK1RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK1RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.
Rolapitant: A Review in Chemotherapy-Induced Nausea and Vomiting. [2019]Oral rolapitant (Varubi™; Varuby®), a long-acting neurokinin-1 (NK1) receptor antagonist (RA), is indicated in the USA and EU as part of an antiemetic regimen to prevent delayed chemotherapy-induced nausea and vomiting (CINV) in adults receiving highly or moderately emetogenic chemotherapy (HEC or MEC). In randomized, phase III trials, a single oral dose of rolapitant 180 mg was effective in preventing delayed CINV compared with placebo, when each was used in combination with a 5-HT3 RA plus dexamethasone, in adults receiving their first course of HEC or MEC. The benefits of rolapitant were maintained over multiple cycles of chemotherapy. The tolerability profile of rolapitant is similar to that of placebo and consistent with that of other NK1 RAs. However, rolapitant differs from other existing NK1 RAs in that it does not interact with CYP3A4, thereby negating the need for dexamethasone dose adjustments and potentially making rolapitant a more suitable option for patients receiving CYP3A4 substrates. Thus, oral rolapitant is an effective and well tolerated NK1 RA that expands the treatment options for preventing delayed CINV in adults receiving HEC or MEC.