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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CVN058, low dose | Active Comparator | 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. |
|
| CVN058, high dose | Active Comparator | CVN058 prepared in concentrations of 10mg/mL, and are compounded by the clinical site. Subjects will receive one dose of CVN058 at 150mg. |
|
| Placebo | Placebo Comparator | Matching placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CVN058 | Drug | CVN058 will be given at two doses, a low does and a high dose |
|
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Susan Kapurch | Cerevance, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States | ||
| New York State Psychiatric Institute |
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A total of 22 eligible participants with schizophrenia including schizoaffective disorder. Eligible participants were randomized to 6 treatment sequences.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Sequence ABC | Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 15 milligrams (mg) in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| FG001 | Treatment Sequence BAC | Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| FG002 | Treatment Sequence CAB | Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| FG003 | Treatment Sequence ACB | Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| FG004 | Treatment Sequence BCA | Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 150 mg in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| FG005 | Treatment Sequence CBA | Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Sequence ABC | Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 15 milligrams (mg) in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Pharmacodynamic Population consisted of all participants who received study drug and had measurements in both the placebo-dosed period and at least one (1) CVN058-dosed period for at least one (1) electroencephalography (EEG)/evoked response endpoint. Only those participants with data available at specified time points has been presented. | Posted | Mean | Standard Deviation | microvolts | 1.5 hours post-dose on Day 1 |
58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants were randomized to receive placebo in each treatment period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michelle Charles, Executive Director Regulatory Affairs | Cerevance | (408) 220-5722 | michelle.charles@cerevance.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 24, 2019 | Jul 5, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 7, 2020 | Jul 5, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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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 to receive 1 of 3 dose regimens in each period; a single oral administration of CVN058, or a matching placebo.
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Double blind, placebo controlled.
| Placebo comparator | Other | inactive placebo |
|
| Screening through 30 days post-dose, up to 58 days |
| New York |
| New York |
| 10032 |
| United States |
| Nathan Kline Institute | New York | New York | 10962 | United States |
| Withdrawal by Subject |
|
| Treatment Sequence BAC |
Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| BG002 | Treatment Sequence CAB | Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| BG003 | Treatment Sequence ACB | Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| BG004 | Treatment Sequence BCA | Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 150 mg in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| BG005 | Treatment Sequence CBA | Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days. |
| BG006 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | analysis was divided between elderly (65 and over) and non elderly (18-65) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Placebo | Participants were randomized to receive Placebo in each treatment period. |
| OG001 | 15mg CVN058 | Participants were randomized to receive CVN058 15 mg in each treatment period |
| OG002 | 75mg CVN058 | Participants were randomized to receive CVN058 75 mg in each treatment period. |
| OG003 | 150 mg CVN058 | Participants were randomized to receive CVN058 150 mg in each treatment period. |
|
|
| Secondary | 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) | Safety Population consisted of all participants who were randomized and received study drug. | Posted | Count of Participants | Participants | Screening through 30 days post-dose, up to 58 days |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 1 |
| 20 |
| EG001 | 15mg CVN058 | Participants were randomized to receive CVN058 15 mg in each treatment period. | 0 | 13 | 0 | 13 | 1 | 13 |
| EG002 | 75mg CVN058 | Participants were randomized to receive CVN058 75 mg in each treatment period. | 0 | 8 | 0 | 8 | 1 | 8 |
| EG003 | 150 mg CVN058 | Participants were randomized to receive CVN058 150 mg in each treatment period. | 0 | 19 | 0 | 19 | 4 | 19 |
| dizziness | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
|
| Blood glucose abnormal | Investigations | MedDRA (21.0) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
|
| Blood sodium abnormal | Investigations | MedDRA (21.0) | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
|
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| Any SAE |
|