Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1U01MH121766-01 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Columbia University | OTHER |
| University of Pennsylvania | OTHER |
| State University of New York Stony Brook | UNKNOWN |
| Cerevel Therapeutics, LLC |
Not provided
Not provided
Not provided
Not provided
This study will test whether CVL-562 (PF-06412562), a dopamine 1 partial agonist novel compound, affects working memory neural circuits in patients with early episode schizophrenia. The overall aim is to establish neuroimaging biomarkers of the Dopamine Receptor 1/Dopamine Receptor 5 Family (D1R/D5R) target engagement to accelerate development of D1R/D5R agonists in humans to treat cognitive impairments that underlie functional disability in schizophrenia, a key unaddressed clinical and public health concern.
This study proposes to examine the effects of CVL-562 (PF-06412562), a dopamine-1 receptor partial agonist, on the neural signal of brain regions involved in cognition in patients with schizophrenia and related psychotic disorders. The primary objective of this study is to understand the neural circuit targets of this compound as it relates to improving cognition in schizophrenia, using a spatial working memory task (sWM). The secondary objective will quantify dose-related drug effects on sWM precision based on behavioral data collected during scanning and examine effects on functional connectivity.
All patients will be psychiatrically stable with early course (psychotic symptom onset within the past 10 years) schizophrenia spectrum disorder (e.g. schizophrenia, schizoaffective disorder, or schizophreniform disorder) and will have working memory deficits (defined as below average performance on the letter n-back task of the PennCNB battery). As part of the study, they will receive oral administration of specified doses of CVL-562 (PF-06412562), in a random order with repeated functional magnetic resonance imaging and cognitive testing during those visits. The most common side effects of this compound are nausea and headache. This is a multi-site study that requires the efforts of 4 study sites in total (Columbia, State University of New York Stony Brook, UPenn, and Yale).
At time of results entry, secondary outcome results unavailable due to ongoing restrictions per the NIH
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CVL-562 (PF-06412562) 1 mg | Experimental | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. |
|
| CVL-562 (PF-06412562) 4 mg | Experimental | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. |
|
| CVL-562 (PF-06412562) 15 mg | Experimental | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CVL-562 (PF-06412562) 1 mg | Drug | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| Measure | Description | Time Frame |
|---|---|---|
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. | Up to two hours for each fMRI session |
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. | Up to two hours for each fMRI session |
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Performance During Spatial Working Memory (sWM) Task | During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. Performance will be assessed with the average accuracy measured during this task for each task condition and each CVL-562 (PF-06412562) dose. Accuracy refers to the angular distance between a cued location and a participant's memory of the location. The range of accuracy is between 0-180 degrees. 0 degrees would indicate the best possible performance, and 180 degrees the worst performance. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| John Krystal, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | New Haven | Connecticut | 06511 | United States | ||
| Columbia University |
De-identified data will be made publicly available through the NIMH Data Archive (NDAR) with data uploaded every 6 months.
Not provided
Six months after publication.
All neuroimaging data will be shared through the National Institute of Mental Health Data Archive (NDA). All requests for accessing these data will be reviewed by the National Institute of Mental Health.
Not provided
Data for participants who started test visits at Columbia was required to be removed due to research restrictions per the NIH (see GCE). Secondary outcome results unavailable due to ongoing restrictions per the NIH.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | All Study Participants | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. All participants will receive all doses (a different dose at each of the 5 visits.) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 4, 2025 |
Not provided
Not provided
| INDUSTRY |
| National Institute of Mental Health (NIMH) | NIH |
Not provided
Not provided
Not provided
Not provided
|
| CVL-562 (PF-06412562) 25 mg | Experimental | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. |
|
| Placebo | Placebo Comparator | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. |
|
| CVL-562 (PF-06412562) 4 mg | Drug | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
|
| CVL-562 (PF-06412562) 15 mg | Drug | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
|
| CVL-562 (PF-06412562) 25 mg | Drug | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
|
| Placebo | Other | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
|
| Up to two hours for each fMRI session |
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. | Up to two hours for each fMRI session |
| Up to two hours for each fMRI session. |
| Association Between Neural Activity and Task Performance | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during fMRI, where subjects will participate in a spatial working memory (sWM) task. The sWM includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. The performance of sWM at each trial of each condition will be used as the predictor variable, and the BOLD signal at the corresponding trial and condition will be used as the outcome variable. A trial refers to a single probing and measurement of sWM, and is repeatedly presented to get a number of sWM measurements. The performance of sWM from each trial will be regressed with the BOLD signal from that trial, and we will report the resulting beta weights at each condition and dose. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). | Up to two hours for each fMRI session. |
| Functional Connectivity Across Brain Regions With the Fronto-parietal Network During sWM Task | Functional connectivity will be assessed during each fMRI session. Functional connectivity refers to the correlation between the time series of different brain regions collected during fMRI. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, the functional connectivity of the fronto-parietal network will be measured with the rest of the brain. The range of functional connectivity is between -4.95 and 4.95. -4.95 would indicate highly negative functional connectivity and 4.95 would indicate highly positive functional connectivity. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). | Up to two hours for each fMRI session. |
| Resting State Global Brain Functional Connectivity | BOLD signal will be collected during the resting state aspect of the fMRI session, using a data-driven global brain connectivity (GBC) metric. GBC examines connectivity from a given voxel (or area) to all other voxels (or areas) simultaneously by computing average connectivity strength. The range of GBC is between -4.95 and 4.95. -4.95 would indicate highly negative broad functional connectivity in synchrony with the rest of the brain and 4.95 would indicate highly positive broad functional connectivity in synchrony with the rest of the brain. GBC will be obtained at each PF-06412562 dose. | Up to two hours for each fMRI session. |
| Proportion of Participants With Change in Blood Oxygen Level Dependent (BOLD) Signal During Spatial Working Memory (sWM) Task. | The dose-response in BOLD signal will be examined for each individual participant to see how many participants exhibit a change in BOLD signal overall. For each individual, binary outcome will be calculated based on a Dose by Condition by Time within subject analysis of BOLD signal. We will report the proportion of participants that exhibits a dose response. | Up to two hours for each fMRI session. |
| Spatial Similarity of Resting State Global Brain Functional Connectivity With Transcriptomic Maps. | Transcriptomics maps will be derived from the Allen Human Brain Atlas (AHBA), which provides gene expression data mapped to the cortical surface. The spatial similarity of resting state global brain functional connectivity (GBC) and gene expression patterns for the D1/D5 receptors will be assessed for each CVL-562 (PF-06412562) dose. The spatial similarity refers to correlation between GBC maps and the cortical gene expression maps. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). | Up to two hours for each fMRI session. |
| New York |
| New York |
| 10032 |
| United States |
| Stony Brook University | Stony Brook | New York | 11794 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Have MRI Data |
|
| Usable Full MRI Data (Analysis Population) | Only full usable MRI data can be analyzed. Participants without full usable MRI data (missing scans, incomplete scans, etc) cannot be analyzed. |
|
| Participants Started at Columbia Site |
|
| Participants Started at All Other Sites | Demographic and Adverse Event results available. |
|
| Received CVL-562 (PF-06412562) 1 mg |
|
| Received CVL-562 (PF-06412562) 4 mg |
|
| Received CVL-562 (PF-06412562) 15 mg |
|
| Received CVL-562 (PF-06412562) 25 mg |
|
| Received Placebo |
|
| COMPLETED | Attended every test visit |
|
| NOT COMPLETED |
|
Baseline characteristics are provided for the 84 participants with available data.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. All participants will receive all doses (a different dose at each of the 5 visits.) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| 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 | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. | Posted | Mean | Standard Deviation | percentage signal change | Up to two hours for each fMRI session |
|
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Performance During Spatial Working Memory (sWM) Task | During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. Performance will be assessed with the average accuracy measured during this task for each task condition and each CVL-562 (PF-06412562) dose. Accuracy refers to the angular distance between a cued location and a participant's memory of the location. The range of accuracy is between 0-180 degrees. 0 degrees would indicate the best possible performance, and 180 degrees the worst performance. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). | Not Posted | Up to two hours for each fMRI session. | Participants | |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Association Between Neural Activity and Task Performance | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during fMRI, where subjects will participate in a spatial working memory (sWM) task. The sWM includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. The performance of sWM at each trial of each condition will be used as the predictor variable, and the BOLD signal at the corresponding trial and condition will be used as the outcome variable. A trial refers to a single probing and measurement of sWM, and is repeatedly presented to get a number of sWM measurements. The performance of sWM from each trial will be regressed with the BOLD signal from that trial, and we will report the resulting beta weights at each condition and dose. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). | Not Posted | Up to two hours for each fMRI session. | Participants | |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Functional Connectivity Across Brain Regions With the Fronto-parietal Network During sWM Task | Functional connectivity will be assessed during each fMRI session. Functional connectivity refers to the correlation between the time series of different brain regions collected during fMRI. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, the functional connectivity of the fronto-parietal network will be measured with the rest of the brain. The range of functional connectivity is between -4.95 and 4.95. -4.95 would indicate highly negative functional connectivity and 4.95 would indicate highly positive functional connectivity. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). | Not Posted | Up to two hours for each fMRI session. | Participants | |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Resting State Global Brain Functional Connectivity | BOLD signal will be collected during the resting state aspect of the fMRI session, using a data-driven global brain connectivity (GBC) metric. GBC examines connectivity from a given voxel (or area) to all other voxels (or areas) simultaneously by computing average connectivity strength. The range of GBC is between -4.95 and 4.95. -4.95 would indicate highly negative broad functional connectivity in synchrony with the rest of the brain and 4.95 would indicate highly positive broad functional connectivity in synchrony with the rest of the brain. GBC will be obtained at each PF-06412562 dose. | Not Posted | Up to two hours for each fMRI session. | Participants | |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Participants With Change in Blood Oxygen Level Dependent (BOLD) Signal During Spatial Working Memory (sWM) Task. | The dose-response in BOLD signal will be examined for each individual participant to see how many participants exhibit a change in BOLD signal overall. For each individual, binary outcome will be calculated based on a Dose by Condition by Time within subject analysis of BOLD signal. We will report the proportion of participants that exhibits a dose response. | Not Posted | Up to two hours for each fMRI session. | Participants | |||||||||||||||||||||||||||||||||||||||||||
| Secondary | Spatial Similarity of Resting State Global Brain Functional Connectivity With Transcriptomic Maps. | Transcriptomics maps will be derived from the Allen Human Brain Atlas (AHBA), which provides gene expression data mapped to the cortical surface. The spatial similarity of resting state global brain functional connectivity (GBC) and gene expression patterns for the D1/D5 receptors will be assessed for each CVL-562 (PF-06412562) dose. The spatial similarity refers to correlation between GBC maps and the cortical gene expression maps. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). | Not Posted | Up to two hours for each fMRI session. | Participants | |||||||||||||||||||||||||||||||||||||||||||
| Primary | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. | Posted | Mean | Standard Deviation | percentage signal change | Up to two hours for each fMRI session |
| ||||||||||||||||||||||||||||||||||||||||
| Primary | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. | Posted | Mean | Standard Deviation | percentage signal change | Up to two hours for each fMRI session |
| ||||||||||||||||||||||||||||||||||||||||
| Primary | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds [total 16s]. Each subject will undergo 5 fMRI sessions, one at each dose. | Posted | Mean | Standard Deviation | percentage signal change | Up to two hours for each fMRI session |
|
21 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CVL-562 (PF-06412562) 1mg | All subjects received 1mg CVL-562 (PF-06412562) | 0 | 84 | 0 | 84 | 20 | 84 |
| EG001 | CVL-562 (PF-06412562) 4mg | All subjects received 4mg CVL-562 (PF-06412562) | 0 | 84 | 0 | 84 | 21 | 84 |
| EG002 | CVL-562 (PF-06412562) 15mg | All subjects received 15mg CVL-562 (PF-06412562) | 0 | 84 | 1 | 84 | 29 | 84 |
| EG003 | CVL-562 (PF-06412562) 25mg | All subjects received 25mg CVL-562 (PF-06412562) | 0 | 84 | 0 | 84 | 35 | 84 |
| EG004 | Placebo | All subjects received Placebo | 0 | 84 | 0 | 84 | 24 | 84 |
| EG005 | Adverse Event Prior to Starting Intervention | Adverse event occurred prior to starting intervention | 0 | 84 | 1 | 84 | 0 | 84 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| worsening pyschosis | Psychiatric disorders | Systematic Assessment |
| ||
| worsening pyschosis | Psychiatric disorders | Systematic Assessment |
| ||
| fall and loss of vision in eye | Eye disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| sleepiness | Nervous system disorders | Systematic Assessment |
| ||
| nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| headache | Nervous system disorders | Systematic Assessment |
| ||
| low energy | General disorders | Systematic Assessment |
| ||
| light-headedness | Nervous system disorders | Systematic Assessment |
| ||
| anxiety | Psychiatric disorders | Systematic Assessment |
| ||
| abdominal discomfort | Gastrointestinal disorders | Systematic Assessment |
| ||
| vomiting | General disorders | Systematic Assessment |
| ||
| worsened psychosis | Psychiatric disorders | Systematic Assessment |
| ||
| Back pain | Nervous system disorders | Systematic Assessment |
|
Secondary outcome data is unavailable at this time due to the ongoing restrictions at the Columbia/New York State Psychiatric Institute (NYSPI) site, preventing data access and sharing described in the approved GCE.
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Krystal, MD | Yale University | 203-785-6396 | john.krystal@yale.edu |
| Aug 25, 2025 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 4, 2023 | Aug 25, 2025 | ICF_001.pdf |
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Second 1.6 |
|
| Second 2.4 |
|
| Second 3.2 |
|
| Second 4.0 |
|
| Second 4.8 |
|
| Second 5.6 |
|
| Second 6.4 |
|
| Second 7.2 |
|
| Second 8.0 |
|
| Second 8.8 |
|
| Second 9.6 |
|
| Second 10.4 |
|
| Second 11.2 |
|
| Second 12.0 |
|
| Second 12.8 |
|
| Second 13.6 |
|
| Second 14.4 |
|
| Second 15.2 |
|
| Second 16.0 |
|
| OG001 | CVL-562 (PF-06412562) 4 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 4 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG002 | CVL-562 (PF-06412562) 15 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 15 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG003 | CVL-562 (PF-06412562) 25 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 25 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG004 | Placebo | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Placebo: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
|
|
| OG001 | CVL-562 (PF-06412562) 4 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 4 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG002 | CVL-562 (PF-06412562) 15 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 15 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG003 | CVL-562 (PF-06412562) 25 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 25 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG004 | Placebo | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Placebo: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
|
|
| OG001 | CVL-562 (PF-06412562) 4 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 4 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG002 | CVL-562 (PF-06412562) 15 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 15 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG003 | CVL-562 (PF-06412562) 25 mg | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. CVL-562 (PF-06412562) 25 mg: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
| OG004 | Placebo | Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed. Placebo: Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)). |
|
|