CVN058 Effect on Mismatch Negativity in Schizophrenics

Study Overview
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Brief Summary
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This is a phase 1, double-blind, placebo-controlled, 3 period cross-over study to evaluate CVN058 target engagement by measuring auditory evoked potential mismatch negativity (MMN) downstream to 5-hydroxytryptamine receptor 3 (5-HT3) as a pharmacodynamic (PD) marker.

Detailed Description
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Male and female subjects with schizophrenia, age 18 to 50 years old, inclusive, will be randomized to 1 of 6 treatment sequences (Table 2.a) to receive 1 of 3 dose regimens in each period: a single oral administration of CVN058 (15 mg or 150 mg) or matching placebo. The sequence will determine the order in which a subject will take each of the 3 regimens. Discontinued subjects may be replaced at the discretion of the sponsor so that approximately 20 completed subjects are available for analysis. The study includes three 1-day treatment periods, with a minimum of 7-day washout, maximum 10 day washout (2 total washouts, after Periods 1 and 2) between periods, and a 7-10 day follow-up call post dosing of the last period. Subjects may be inpatients or outpatients at the discretion of the Investigator.

Official Title
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A Placebo-Controlled Study to Evaluate the Effect of a Single Dose of CVN058 on Mismatch Negativity in Subjects With Stable Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: CVN058
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 18 to 50 years of age, inclusive, at the time of informed consent. The subject weighs at least 50 kg and has a body mass index (BMI) between 18 and 40 kg/m2 inclusive at Screening. Subject meets schizophrenia criteria as defined by the Diagnostic & Statistical Manual of mental Disorders, 5th Edition (DSM-V). Subjects are on a stable dose of antipsychotic medication(s) for at least 2 months prior to - Screening as documented by medical history and assessed by site staff. Subject has a Positive and Negative Syndrome Scale (PANSS) total score of <95. Exclusion Criteria: Subject currently receiving treatment with any excluded medication or dietary supplement. Subjects who have a history of gastrointestinal disease that would influence the absorption of study drug or have a history of any surgical intervention known to impact absorption (e.g., bariatric surgery or bowel resection). Subjects having clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis) outside the reference range for the testing laboratory, unless the results are deemed to be not clinically significant (NCS) by the investigator at Screening. Subjects with moderate to severe substance use disorder, unstable mood or anxiety disorder. Subject has a current diagnosis of a significant psychiatric illness other than schizophrenia per DSM-V and is in an acute phase/episode. Subject has clinically meaningful hearing loss.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Male and female subjects with schizophrenia, age 18 to 50 years old, inclusive, will be randomized to 1 of 6 treatment sequences to receive 1 of 3 dose regimens in each period; a single oral administration of CVN058, or a matching placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CVN058, low dose<br>CVN058 prepared in concentrations of 10mg/mL, and are compounded by the clinical site. Subjects will receive one dose of CVN058 at 15mg or 75mg substitution of 15mg. | Drug: CVN058<br>* 3-way crossover<br>|
| Active Comparator: CVN058, high dose<br>CVN058 prepared in concentrations of 10mg/mL, and are compounded by the clinical site. Subjects will receive one dose of CVN058 at 150mg. | Drug: CVN058<br>* 3-way crossover<br>|
| Placebo Comparator: Placebo<br>Matching placebo. | Drug: Placebos<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Electroencephalogram, Mismatch Negativity (MMN) | Mean amplitude of duration MMN following administration of CVN058 compared to placebo. | 1.5 hours post-dose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of adverse events | Occurrence of all adverse events from signing of informed consent through end of study treatment | Screening through 30 days post-dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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auditory gating, MMN, EEG, P50, gamma power, P300