CVN058 Effect on Mismatch Negativity in Schizophrenics

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: CVN058; Other: Placebo comparator

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute
    • New York, New York, United States, 10962
      • Nathan Kline Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo.	Other: Placebo comparator; inactive placebo
Active Comparator: CVN058, low dose; 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; CVN058 will be given at two doses, a low does and a high dose; Other Names: TAK058
Active Comparator: CVN058, high dose; 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; CVN058 will be given at two doses, a low does and a high dose; Other Names: TAK058

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Amplitude of Duration of Auditory Mismatch Negativity (MMN) by Dose Level	MMN is a pre-attentive auditory component elicited by deviant stimuli in an auditory oddball task. Participants were repeatedly exposed to auditory tones and a small proportion of those tones (the "deviant" stimuli) differ from the others (the "standard" stimuli) in their frequency or duration. Typically, the tones are presented, and the evoked potentials are recorded while participants are engaged on a different task, such as reading. Normally, the occurrence of a deviant stimulus increases the amplitude of the negative component in the evoked potential occurring at around 200 msec. MMN is the difference in amplitude between deviant and standard stimuli responses and considered to represent an aspect of pre-attentive novelty detection.	1.5 hours post-dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. TEAEs are defined as any event with onset during or after the first dose of study treatment (active or placebo)	Screening through 30 days post-dose, up to 58 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Electroencephalogram, Gamma Power	EEG measurements of delta (0.5 - 4 Hz), theta (4-7 Hz), alpha (8-13 Hz), delta (13-20 Hz), low gamma (20-40 Hz) and high gamma (40 - 60 Hz).	1.5 hours post-dose on Day 1
Quantitative Electroencephalogram, P300	EEG measurement of peak amplitude within prespecified latency range at the frontal/parietal sites.	1.5 hours post-dose on Day 1
Quantitative Electroencephalogram, P50	EEG measurement of stimulus signal of 90-dB pulses of 0.1 msec in duration.	1.5 hours post-dose on Day 1

Collaborators and Investigators

• Sponsor: Cerevance Alpha, Inc.
• Investigators: Study Chair: Susan Kapurch, Cerevance, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2018
• Primary Completion (Actual): March 6, 2020
• Study Completion (Actual): March 6, 2020

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: EEG; P50; P300; MMN; gamma power; auditory gating
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: CVN058-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No