CVN058 Effect on Mismatch Negativity in Schizophrenics

Sponsor

Cerevance Alpha, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03669250

Collaborator

(none)

Enrollment

Locations

Arms

15.9

Actual Duration (Months)

6.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: CVN058 Drug: Placebos	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention 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.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 (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double blind, placebo controlled.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 9, 2018

Actual Primary Completion Date :

Mar 6, 2020

Actual Study Completion Date :

Mar 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
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 3-way crossover
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 3-way crossover
Placebo Comparator: Placebo Matching placebo.	Drug: Placebos Placebo

Arm

Intervention/Treatment

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

3-way crossover

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

3-way crossover

Placebo Comparator: Placebo

Matching placebo.

Drug: Placebos

Placebo

Outcome Measures

Primary Outcome Measures

Quantitative Electroencephalogram, Mismatch Negativity (MMN) [1.5 hours post-dose on Day 1]
Mean amplitude of duration MMN following administration of CVN058 compared to placebo.

Secondary Outcome Measures

Evaluation of adverse events [Screening through 30 days post-dose.]
Occurrence of all adverse events from signing of informed consent through end of study treatment

Other Outcome Measures

Quantitative Electroencephalogram, Gamma Power [1.5 hours post-dose on Day 1]
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).
Quantitative Electroencephalogram, P300 [1.5 hours post-dose on Day 1]
EEG measurement of peak amplitude within prespecified latency range at the frontal/parietal sites.
Quantitative Electroencephalogram, P50 [1.5 hours post-dose on Day 1]
EEG measurement of stimulus signal of 90-dB pulses of 0.1 msec in duration.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
2	New York State Psychiatric Institute	New York	New York	United States	10032
3	Nathan Kline Institute	New York	New York	United States	10962