Nezavist for Safety Evaluation

Overseen By Administrative Assistant

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Lohocla Research Corporation

Must not be taking: CYP3A4 inhibitors, MAOIs

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

Compensation: Varies

Number of Visits: 2

Duration: 3 days

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, participants must stop taking any over-the-counter or prescription medications, vitamins, and herbal supplements at least 2 weeks before the study drug is given.

What safety data exists for Nezavist or similar treatments?

The research articles discuss general drug safety data, adverse drug event reporting, and methods for identifying drug adverse reactions, but they do not provide specific safety information about Nezavist or similar treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

The goal of this clinical trial is to determine the safety, tolerability and effects of Nezavist in healthy adults. The main questions it aims to answer are: * What is the safety and maximum tolerated dose (MTD) of orally administered Nezavist formulated as a spray dried dispersion (SDD) in healthy volunteers? * What are the pharmacokinetics (PK) of orally administered Nezavist SDD and its major metabolite (DCUKA) across a range of doses in healthy volunteers? Researchers will compare the active drug (Nezavist) and a placebo (an inactive substance that looks like the drug) to see if there is any differences between the two groups to make sure Nezavist is safe to use in future studies for reducing alcohol consumption by individuals that have alcohol use disorder (AUD).

Research Team

Mark Wallace, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for healthy adults who can safely participate in a study to determine the safety and tolerability of Nezavist, an experimental drug. Participants must meet specific health requirements but detailed inclusion and exclusion criteria are not provided.

Inclusion Criteria

2. BMI must be between 18 and 32 kg/m\^2 (inclusive) and weigh a minimum of 50 kg (110 lbs). BMI is calculated as weight in kg divided by the square of height measured in meters.

3. A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG) at the screening visit.

* Vasectomized partner (at least 6 months prior to dosing)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive Nezavist SDD oral suspension or placebo and remain in the clinic for safety assessments and blood collections

3 days

Continuous stay (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 days

1 visit (in-person)

Treatment Details

Interventions

• Nezavist

Trial Overview The trial tests different doses of Nezavist, given orally as a spray dried dispersion (SDD), against a placebo. It aims to find out the maximum tolerated dose and how the body processes the drug and its main metabolite.

Participant Groups

Group I: Nezavist Cohort 4 Experimental Treatment 1 Intervention

Nezavist 13500 mg in a volume of 60 mL NPO 8 hrs AM bib.

Group II: Nezavist Cohort 3 Experimental Treatment 1 Intervention

Nezavist 4500 mg in a volume of 60 mL NPO 8 hrs AM bib.

Group III: Nezavist Cohort 1 Active Control 1 Intervention

Nezavist 500 mg in a volume of 60 mL NPO 8 hrs AM bib.

Group IV: Nezavist Cohort 2 Active Control 1 Intervention

Nezavist 1500 mg in a volume of 60 mL NPO 8 hrs AM bib.

Group V: Placebo Placebo Group 1 Intervention

Placebo to match 5.4 g of Avicel in a volume of 60 mL NPO 8 hrs AM bib.

Who Is Running the Clinical Trial?

Lohocla Research Corporation

Lead Sponsor

Trials

2

Recruited

60+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

A systematic review of 108 adverse drug event (ADE) reporting systems revealed 1782 unique data fields, highlighting significant variability in how ADEs are reported, which complicates data comparison and aggregation across different systems.

Despite consistent reporting concepts, the lack of standardized terminology and the use of multiple drug and disease dictionaries hinder effective drug safety monitoring, suggesting a need for a common standardized dataset to improve ADE reporting and surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug event reporting systems: a systematic review. Bailey, C., Peddie, D., Wickham, ME., et al.[2021]

The SMART Safety dataset is the largest collection of empirical data on adverse events in healthcare, comprising 151 systematic reviews and 629 meta-analyses, which enhances the understanding of safety outcomes in randomized controlled trials.

This dataset, which includes over 2,300 trials and 362 harm outcomes, has been rigorously validated to ensure high data quality, providing a valuable resource for addressing rare adverse events and biases in evidence synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SMART Safety: An empirical dataset for evidence synthesis of adverse events. Fan, S., Yu, T., Yang, X., et al.[2023]

The study developed an automated method to aggregate various sources of drug safety information, achieving high predictive accuracy (≥0.92) in classifying drug-adverse event relationships, which can significantly streamline the process of identifying drugs associated with adverse reactions.

This approach offers a scalable alternative to the traditional manual curation methods, potentially saving time and resources in drug safety research by efficiently creating reference sets of drugs that do or do not cause adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accuracy of an automated knowledge base for identifying drug adverse reactions. Voss, EA., Boyce, RD., Ryan, PB., et al.[2019]

The term 'adverse events' is the most commonly used in medical literature to describe negative outcomes related to healthcare, highlighting its importance in patient safety research.

The primary focus of adverse events research is to understand these events as outcomes, with data primarily sourced from patient clinical records and self-reports by healthcare professionals, indicating a need for more comprehensive studies in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in acute care: an integrative literature review. Kellogg, VA., Havens, DS.[2022]

References

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

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Adverse drug event reporting systems: a systematic review. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The SMART Safety: An empirical dataset for evidence synthesis of adverse events. [2023]

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

Accuracy of an automated knowledge base for identifying drug adverse reactions. [2019]

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

Adverse events in acute care: an integrative literature review. [2022]