Clinical trial NCT03669250: CVN058 Effect on Mismatch Negativity in Schizophrenics
Official title: A Placebo-Controlled Study to Evaluate the Effect of a Single Dose of CVN058 on Mismatch Negativity in Subjects With Stable Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: MMN
EEG
P50
gamma power
P300
auditory gating
Lead sponsor: Cerevance
Sponsor class: INDUSTRY
First posted: 2018-09-13
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Amplitude of Duration of Auditory Mismatch Negativity (MMN) by Dose Level
timeFrame: 1.5 hours post-dose on Day 1
Secondary outcomes:
measure: Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Screening through 30 days post-dose, up to 58 days
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: New York
country: United States
facility: Nathan Kline Institute
state: New York
Study officials:
affiliation: Cerevance, Inc.
name: Susan Kapurch
role: STUDY_CHAIR
References: