Trial Outcomes & Findings for A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia (NCT NCT04457310)
NCT ID: NCT04457310
Last Updated: 2025-10-15
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
112 participants
Primary outcome timeframe
Up to two hours for each fMRI session
Results posted on
2025-10-15
Participant Flow
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.
Participant milestones
| Measure |
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.)
|
|---|---|
|
Overall Study
STARTED
|
112
|
|
Overall Study
Have MRI Data
|
52
|
|
Overall Study
Usable Full MRI Data (Analysis Population)
|
50
|
|
Overall Study
Participants Started at Columbia Site
|
28
|
|
Overall Study
Participants Started at All Other Sites
|
84
|
|
Overall Study
Received CVL-562 (PF-06412562) 1 mg
|
78
|
|
Overall Study
Received CVL-562 (PF-06412562) 4 mg
|
77
|
|
Overall Study
Received CVL-562 (PF-06412562) 15 mg
|
75
|
|
Overall Study
Received CVL-562 (PF-06412562) 25 mg
|
70
|
|
Overall Study
Received Placebo
|
77
|
|
Overall Study
COMPLETED
|
71
|
|
Overall Study
NOT COMPLETED
|
41
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Translational and Neurocomputational Evaluation of a Dopamine Receptor 1 Partial Agonist for Schizophrenia
Baseline characteristics by cohort
| Measure |
All Study Participants
n=84 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.)
|
|---|---|
|
Age, Continuous
|
27.06 years
STANDARD_DEVIATION 5.03 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
62 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
84 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to two hours for each fMRI sessionNeural 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.
Outcome measures
| Measure |
CVL-562 (PF-06412562) 1 mg
n=50 Participants
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) 1 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)).
|
CVL-562 (PF-06412562) 4 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 15 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 25 mg
n=50 Participants
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)).
|
Placebo
n=50 Participants
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)).
|
|---|---|---|---|---|---|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 0.8
|
-0.076 percentage signal change
Standard Deviation 0.165
|
-0.090 percentage signal change
Standard Deviation 0.177
|
-0.072 percentage signal change
Standard Deviation 0.180
|
-0.136 percentage signal change
Standard Deviation 0.169
|
-0.064 percentage signal change
Standard Deviation 0.161
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 1.6
|
-0.090 percentage signal change
Standard Deviation 0.217
|
-0.097 percentage signal change
Standard Deviation 0.225
|
-0.083 percentage signal change
Standard Deviation 0.223
|
-0.167 percentage signal change
Standard Deviation 0.207
|
-0.067 percentage signal change
Standard Deviation 0.212
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 2.4
|
-0.045 percentage signal change
Standard Deviation 0.235
|
-0.042 percentage signal change
Standard Deviation 0.231
|
-0.039 percentage signal change
Standard Deviation 0.235
|
-0.135 percentage signal change
Standard Deviation 0.213
|
-0.043 percentage signal change
Standard Deviation 0.232
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 3.2
|
0.024 percentage signal change
Standard Deviation 0.238
|
0.028 percentage signal change
Standard Deviation 0.239
|
0.031 percentage signal change
Standard Deviation 0.245
|
-0.066 percentage signal change
Standard Deviation 0.228
|
0.020 percentage signal change
Standard Deviation 0.223
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 4.0
|
0.092 percentage signal change
Standard Deviation 0.240
|
0.094 percentage signal change
Standard Deviation 0.256
|
0.104 percentage signal change
Standard Deviation 0.246
|
-0.012 percentage signal change
Standard Deviation 0.235
|
0.072 percentage signal change
Standard Deviation 0.237
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 4.8
|
0.119 percentage signal change
Standard Deviation 0.261
|
0.137 percentage signal change
Standard Deviation 0.259
|
0.143 percentage signal change
Standard Deviation 0.257
|
0.027 percentage signal change
Standard Deviation 0.251
|
0.110 percentage signal change
Standard Deviation 0.248
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 5.6
|
0.105 percentage signal change
Standard Deviation 0.271
|
0.144 percentage signal change
Standard Deviation 0.263
|
0.153 percentage signal change
Standard Deviation 0.265
|
0.033 percentage signal change
Standard Deviation 0.246
|
0.113 percentage signal change
Standard Deviation 0.246
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 6.4
|
0.078 percentage signal change
Standard Deviation 0.280
|
0.118 percentage signal change
Standard Deviation 0.256
|
0.127 percentage signal change
Standard Deviation 0.260
|
0.006 percentage signal change
Standard Deviation 0.243
|
0.100 percentage signal change
Standard Deviation 0.257
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 7.2
|
0.038 percentage signal change
Standard Deviation 0.287
|
0.097 percentage signal change
Standard Deviation 0.257
|
0.086 percentage signal change
Standard Deviation 0.251
|
-0.028 percentage signal change
Standard Deviation 0.239
|
0.061 percentage signal change
Standard Deviation 0.254
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 8.0
|
-0.009 percentage signal change
Standard Deviation 0.294
|
0.064 percentage signal change
Standard Deviation 0.260
|
0.055 percentage signal change
Standard Deviation 0.238
|
-0.059 percentage signal change
Standard Deviation 0.228
|
0.025 percentage signal change
Standard Deviation 0.259
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 8.8
|
-0.036 percentage signal change
Standard Deviation 0.292
|
0.045 percentage signal change
Standard Deviation 0.248
|
0.020 percentage signal change
Standard Deviation 0.227
|
-0.087 percentage signal change
Standard Deviation 0.220
|
0.001 percentage signal change
Standard Deviation 0.262
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 9.6
|
-0.045 percentage signal change
Standard Deviation 0.288
|
0.032 percentage signal change
Standard Deviation 0.242
|
-0.007 percentage signal change
Standard Deviation 0.230
|
-0.091 percentage signal change
Standard Deviation 0.207
|
-0.020 percentage signal change
Standard Deviation 0.247
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 10.4
|
-0.054 percentage signal change
Standard Deviation 0.289
|
0.027 percentage signal change
Standard Deviation 0.235
|
-0.015 percentage signal change
Standard Deviation 0.237
|
-0.093 percentage signal change
Standard Deviation 0.209
|
-0.030 percentage signal change
Standard Deviation 0.253
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 11.2
|
-0.049 percentage signal change
Standard Deviation 0.292
|
0.036 percentage signal change
Standard Deviation 0.237
|
-0.012 percentage signal change
Standard Deviation 0.232
|
-0.092 percentage signal change
Standard Deviation 0.212
|
-0.038 percentage signal change
Standard Deviation 0.248
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 12.0
|
-0.025 percentage signal change
Standard Deviation 0.289
|
0.051 percentage signal change
Standard Deviation 0.250
|
-0.005 percentage signal change
Standard Deviation 0.240
|
-0.073 percentage signal change
Standard Deviation 0.216
|
-0.034 percentage signal change
Standard Deviation 0.258
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 12.8
|
-0.017 percentage signal change
Standard Deviation 0.275
|
0.049 percentage signal change
Standard Deviation 0.243
|
0.003 percentage signal change
Standard Deviation 0.247
|
-0.052 percentage signal change
Standard Deviation 0.216
|
-0.033 percentage signal change
Standard Deviation 0.262
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 13.6
|
0.015 percentage signal change
Standard Deviation 0.275
|
0.072 percentage signal change
Standard Deviation 0.238
|
0.033 percentage signal change
Standard Deviation 0.257
|
-0.025 percentage signal change
Standard Deviation 0.214
|
-0.004 percentage signal change
Standard Deviation 0.271
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 14.4
|
0.073 percentage signal change
Standard Deviation 0.278
|
0.124 percentage signal change
Standard Deviation 0.242
|
0.083 percentage signal change
Standard Deviation 0.269
|
0.028 percentage signal change
Standard Deviation 0.223
|
0.056 percentage signal change
Standard Deviation 0.281
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 15.2
|
0.138 percentage signal change
Standard Deviation 0.281
|
0.177 percentage signal change
Standard Deviation 0.248
|
0.153 percentage signal change
Standard Deviation 0.288
|
0.091 percentage signal change
Standard Deviation 0.238
|
0.127 percentage signal change
Standard Deviation 0.287
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Second 16.0
|
0.187 percentage signal change
Standard Deviation 0.290
|
0.229 percentage signal change
Standard Deviation 0.251
|
0.225 percentage signal change
Standard Deviation 0.310
|
0.130 percentage signal change
Standard Deviation 0.277
|
0.175 percentage signal change
Standard Deviation 0.297
|
PRIMARY outcome
Timeframe: Up to two hours for each fMRI sessionNeural 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.
Outcome measures
| Measure |
CVL-562 (PF-06412562) 1 mg
n=50 Participants
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) 1 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)).
|
CVL-562 (PF-06412562) 4 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 15 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 25 mg
n=50 Participants
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)).
|
Placebo
n=50 Participants
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)).
|
|---|---|---|---|---|---|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 0.8
|
-0.070 percentage signal change
Standard Deviation 0.155
|
-0.040 percentage signal change
Standard Deviation 0.148
|
-0.060 percentage signal change
Standard Deviation 0.164
|
-0.065 percentage signal change
Standard Deviation 0.151
|
-0.081 percentage signal change
Standard Deviation 0.152
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 1.6
|
-0.086 percentage signal change
Standard Deviation 0.200
|
-0.036 percentage signal change
Standard Deviation 0.197
|
-0.076 percentage signal change
Standard Deviation 0.218
|
-0.079 percentage signal change
Standard Deviation 0.184
|
-0.093 percentage signal change
Standard Deviation 0.187
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 2.4
|
-0.042 percentage signal change
Standard Deviation 0.200
|
0.013 percentage signal change
Standard Deviation 0.214
|
-0.039 percentage signal change
Standard Deviation 0.216
|
-0.045 percentage signal change
Standard Deviation 0.197
|
-0.053 percentage signal change
Standard Deviation 0.198
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 3.2
|
0.025 percentage signal change
Standard Deviation 0.228
|
0.074 percentage signal change
Standard Deviation 0.225
|
0.025 percentage signal change
Standard Deviation 0.220
|
0.010 percentage signal change
Standard Deviation 0.193
|
0.012 percentage signal change
Standard Deviation 0.204
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 4.0
|
0.071 percentage signal change
Standard Deviation 0.243
|
0.131 percentage signal change
Standard Deviation 0.223
|
0.081 percentage signal change
Standard Deviation 0.245
|
0.060 percentage signal change
Standard Deviation 0.207
|
0.068 percentage signal change
Standard Deviation 0.216
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 4.8
|
0.089 percentage signal change
Standard Deviation 0.243
|
0.151 percentage signal change
Standard Deviation 0.223
|
0.109 percentage signal change
Standard Deviation 0.266
|
0.091 percentage signal change
Standard Deviation 0.224
|
0.098 percentage signal change
Standard Deviation 0.224
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 5.6
|
0.087 percentage signal change
Standard Deviation 0.251
|
0.145 percentage signal change
Standard Deviation 0.219
|
0.096 percentage signal change
Standard Deviation 0.287
|
0.089 percentage signal change
Standard Deviation 0.228
|
0.090 percentage signal change
Standard Deviation 0.228
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 6.4
|
0.054 percentage signal change
Standard Deviation 0.255
|
0.126 percentage signal change
Standard Deviation 0.212
|
0.067 percentage signal change
Standard Deviation 0.280
|
0.067 percentage signal change
Standard Deviation 0.236
|
0.059 percentage signal change
Standard Deviation 0.237
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 7.2
|
0.011 percentage signal change
Standard Deviation 0.250
|
0.088 percentage signal change
Standard Deviation 0.213
|
0.032 percentage signal change
Standard Deviation 0.279
|
0.040 percentage signal change
Standard Deviation 0.238
|
0.032 percentage signal change
Standard Deviation 0.245
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 8.0
|
-0.013 percentage signal change
Standard Deviation 0.254
|
0.056 percentage signal change
Standard Deviation 0.207
|
-0.009 percentage signal change
Standard Deviation 0.273
|
0.019 percentage signal change
Standard Deviation 0.243
|
0.000 percentage signal change
Standard Deviation 0.240
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 8.8
|
-0.038 percentage signal change
Standard Deviation 0.256
|
0.043 percentage signal change
Standard Deviation 0.216
|
-0.033 percentage signal change
Standard Deviation 0.269
|
-0.010 percentage signal change
Standard Deviation 0.228
|
-0.018 percentage signal change
Standard Deviation 0.242
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 9.6
|
-0.056 percentage signal change
Standard Deviation 0.258
|
0.027 percentage signal change
Standard Deviation 0.223
|
-0.038 percentage signal change
Standard Deviation 0.265
|
-0.022 percentage signal change
Standard Deviation 0.223
|
-0.042 percentage signal change
Standard Deviation 0.246
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 10.4
|
-0.068 percentage signal change
Standard Deviation 0.246
|
0.024 percentage signal change
Standard Deviation 0.214
|
-0.032 percentage signal change
Standard Deviation 0.267
|
-0.031 percentage signal change
Standard Deviation 0.216
|
-0.042 percentage signal change
Standard Deviation 0.237
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 11.2
|
-0.053 percentage signal change
Standard Deviation 0.233
|
0.028 percentage signal change
Standard Deviation 0.210
|
-0.024 percentage signal change
Standard Deviation 0.267
|
-0.038 percentage signal change
Standard Deviation 0.206
|
-0.044 percentage signal change
Standard Deviation 0.233
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 12.0
|
-0.041 percentage signal change
Standard Deviation 0.235
|
0.032 percentage signal change
Standard Deviation 0.211
|
0.000 percentage signal change
Standard Deviation 0.269
|
-0.040 percentage signal change
Standard Deviation 0.229
|
-0.038 percentage signal change
Standard Deviation 0.235
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 12.8
|
-0.026 percentage signal change
Standard Deviation 0.241
|
0.037 percentage signal change
Standard Deviation 0.227
|
0.005 percentage signal change
Standard Deviation 0.272
|
-0.029 percentage signal change
Standard Deviation 0.217
|
-0.029 percentage signal change
Standard Deviation 0.236
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 13.6
|
0.014 percentage signal change
Standard Deviation 0.246
|
0.077 percentage signal change
Standard Deviation 0.231
|
0.046 percentage signal change
Standard Deviation 0.273
|
0.002 percentage signal change
Standard Deviation 0.222
|
0.019 percentage signal change
Standard Deviation 0.242
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 14.4
|
0.079 percentage signal change
Standard Deviation 0.251
|
0.142 percentage signal change
Standard Deviation 0.234
|
0.101 percentage signal change
Standard Deviation 0.281
|
0.056 percentage signal change
Standard Deviation 0.235
|
0.086 percentage signal change
Standard Deviation 0.249
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 15.2
|
0.146 percentage signal change
Standard Deviation 0.279
|
0.203 percentage signal change
Standard Deviation 0.246
|
0.165 percentage signal change
Standard Deviation 0.290
|
0.134 percentage signal change
Standard Deviation 0.246
|
0.150 percentage signal change
Standard Deviation 0.269
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Second 16.0
|
0.200 percentage signal change
Standard Deviation 0.286
|
0.247 percentage signal change
Standard Deviation 0.265
|
0.209 percentage signal change
Standard Deviation 0.307
|
0.172 percentage signal change
Standard Deviation 0.258
|
0.204 percentage signal change
Standard Deviation 0.287
|
PRIMARY outcome
Timeframe: Up to two hours for each fMRI sessionNeural 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.
Outcome measures
| Measure |
CVL-562 (PF-06412562) 1 mg
n=50 Participants
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) 1 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)).
|
CVL-562 (PF-06412562) 4 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 15 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 25 mg
n=50 Participants
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)).
|
Placebo
n=50 Participants
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)).
|
|---|---|---|---|---|---|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 0.8
|
-0.108 percentage signal change
Standard Deviation 0.134
|
-0.100 percentage signal change
Standard Deviation 0.112
|
-0.122 percentage signal change
Standard Deviation 0.130
|
-0.072 percentage signal change
Standard Deviation 0.119
|
-0.122 percentage signal change
Standard Deviation 0.095
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 1.6
|
-0.108 percentage signal change
Standard Deviation 0.150
|
-0.116 percentage signal change
Standard Deviation 0.118
|
-0.129 percentage signal change
Standard Deviation 0.137
|
-0.077 percentage signal change
Standard Deviation 0.127
|
-0.128 percentage signal change
Standard Deviation 0.105
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 2.4
|
-0.063 percentage signal change
Standard Deviation 0.153
|
-0.072 percentage signal change
Standard Deviation 0.122
|
-0.073 percentage signal change
Standard Deviation 0.137
|
-0.043 percentage signal change
Standard Deviation 0.127
|
-0.078 percentage signal change
Standard Deviation 0.099
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 3.2
|
0.017 percentage signal change
Standard Deviation 0.147
|
-0.004 percentage signal change
Standard Deviation 0.122
|
-0.003 percentage signal change
Standard Deviation 0.131
|
0.025 percentage signal change
Standard Deviation 0.121
|
0.004 percentage signal change
Standard Deviation 0.111
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 4.0
|
0.074 percentage signal change
Standard Deviation 0.151
|
0.044 percentage signal change
Standard Deviation 0.134
|
0.053 percentage signal change
Standard Deviation 0.127
|
0.069 percentage signal change
Standard Deviation 0.114
|
0.054 percentage signal change
Standard Deviation 0.116
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 4.8
|
0.108 percentage signal change
Standard Deviation 0.145
|
0.067 percentage signal change
Standard Deviation 0.134
|
0.087 percentage signal change
Standard Deviation 0.129
|
0.102 percentage signal change
Standard Deviation 0.105
|
0.074 percentage signal change
Standard Deviation 0.116
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 5.6
|
0.100 percentage signal change
Standard Deviation 0.162
|
0.072 percentage signal change
Standard Deviation 0.120
|
0.095 percentage signal change
Standard Deviation 0.128
|
0.095 percentage signal change
Standard Deviation 0.110
|
0.070 percentage signal change
Standard Deviation 0.115
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 6.4
|
0.086 percentage signal change
Standard Deviation 0.167
|
0.051 percentage signal change
Standard Deviation 0.122
|
0.079 percentage signal change
Standard Deviation 0.126
|
0.058 percentage signal change
Standard Deviation 0.109
|
0.046 percentage signal change
Standard Deviation 0.110
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 7.2
|
0.062 percentage signal change
Standard Deviation 0.171
|
0.035 percentage signal change
Standard Deviation 0.132
|
0.059 percentage signal change
Standard Deviation 0.111
|
0.040 percentage signal change
Standard Deviation 0.104
|
0.033 percentage signal change
Standard Deviation 0.110
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 8.0
|
0.052 percentage signal change
Standard Deviation 0.159
|
0.042 percentage signal change
Standard Deviation 0.128
|
0.059 percentage signal change
Standard Deviation 0.111
|
0.048 percentage signal change
Standard Deviation 0.098
|
0.037 percentage signal change
Standard Deviation 0.103
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 8.8
|
0.084 percentage signal change
Standard Deviation 0.145
|
0.083 percentage signal change
Standard Deviation 0.143
|
0.095 percentage signal change
Standard Deviation 0.113
|
0.089 percentage signal change
Standard Deviation 0.104
|
0.074 percentage signal change
Standard Deviation 0.098
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 9.6
|
0.127 percentage signal change
Standard Deviation 0.146
|
0.119 percentage signal change
Standard Deviation 0.147
|
0.128 percentage signal change
Standard Deviation 0.109
|
0.125 percentage signal change
Standard Deviation 0.113
|
0.115 percentage signal change
Standard Deviation 0.109
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 10.4
|
0.158 percentage signal change
Standard Deviation 0.140
|
0.130 percentage signal change
Standard Deviation 0.136
|
0.126 percentage signal change
Standard Deviation 0.109
|
0.147 percentage signal change
Standard Deviation 0.127
|
0.141 percentage signal change
Standard Deviation 0.119
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 11.2
|
0.161 percentage signal change
Standard Deviation 0.141
|
0.125 percentage signal change
Standard Deviation 0.144
|
0.116 percentage signal change
Standard Deviation 0.128
|
0.139 percentage signal change
Standard Deviation 0.137
|
0.144 percentage signal change
Standard Deviation 0.119
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 12.0
|
0.136 percentage signal change
Standard Deviation 0.141
|
0.094 percentage signal change
Standard Deviation 0.153
|
0.094 percentage signal change
Standard Deviation 0.123
|
0.117 percentage signal change
Standard Deviation 0.142
|
0.117 percentage signal change
Standard Deviation 0.125
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 12.8
|
0.107 percentage signal change
Standard Deviation 0.147
|
0.057 percentage signal change
Standard Deviation 0.149
|
0.063 percentage signal change
Standard Deviation 0.113
|
0.085 percentage signal change
Standard Deviation 0.130
|
0.086 percentage signal change
Standard Deviation 0.129
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 13.6
|
0.091 percentage signal change
Standard Deviation 0.137
|
0.049 percentage signal change
Standard Deviation 0.137
|
0.042 percentage signal change
Standard Deviation 0.114
|
0.077 percentage signal change
Standard Deviation 0.125
|
0.077 percentage signal change
Standard Deviation 0.134
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 14.4
|
0.116 percentage signal change
Standard Deviation 0.135
|
0.065 percentage signal change
Standard Deviation 0.140
|
0.068 percentage signal change
Standard Deviation 0.118
|
0.094 percentage signal change
Standard Deviation 0.134
|
0.098 percentage signal change
Standard Deviation 0.140
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 15.2
|
0.148 percentage signal change
Standard Deviation 0.145
|
0.095 percentage signal change
Standard Deviation 0.162
|
0.108 percentage signal change
Standard Deviation 0.141
|
0.129 percentage signal change
Standard Deviation 0.142
|
0.138 percentage signal change
Standard Deviation 0.150
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Second 16.0
|
0.180 percentage signal change
Standard Deviation 0.182
|
0.131 percentage signal change
Standard Deviation 0.171
|
0.165 percentage signal change
Standard Deviation 0.164
|
0.169 percentage signal change
Standard Deviation 0.156
|
0.181 percentage signal change
Standard Deviation 0.160
|
PRIMARY outcome
Timeframe: Up to two hours for each fMRI sessionNeural 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.
Outcome measures
| Measure |
CVL-562 (PF-06412562) 1 mg
n=50 Participants
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) 1 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)).
|
CVL-562 (PF-06412562) 4 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 15 mg
n=50 Participants
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)).
|
CVL-562 (PF-06412562) 25 mg
n=50 Participants
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)).
|
Placebo
n=50 Participants
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)).
|
|---|---|---|---|---|---|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 7.2
|
0.048 percentage signal change
Standard Deviation 0.141
|
0.017 percentage signal change
Standard Deviation 0.147
|
0.051 percentage signal change
Standard Deviation 0.133
|
0.010 percentage signal change
Standard Deviation 0.142
|
0.021 percentage signal change
Standard Deviation 0.106
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 6.4
|
0.068 percentage signal change
Standard Deviation 0.141
|
0.028 percentage signal change
Standard Deviation 0.140
|
0.078 percentage signal change
Standard Deviation 0.131
|
0.039 percentage signal change
Standard Deviation 0.139
|
0.044 percentage signal change
Standard Deviation 0.109
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 0.8
|
-0.124 percentage signal change
Standard Deviation 0.119
|
-0.120 percentage signal change
Standard Deviation 0.134
|
-0.133 percentage signal change
Standard Deviation 0.118
|
-0.137 percentage signal change
Standard Deviation 0.109
|
-0.110 percentage signal change
Standard Deviation 0.124
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 1.6
|
-0.120 percentage signal change
Standard Deviation 0.133
|
-0.123 percentage signal change
Standard Deviation 0.144
|
-0.138 percentage signal change
Standard Deviation 0.132
|
-0.146 percentage signal change
Standard Deviation 0.113
|
-0.109 percentage signal change
Standard Deviation 0.137
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 2.4
|
-0.079 percentage signal change
Standard Deviation 0.139
|
-0.090 percentage signal change
Standard Deviation 0.134
|
-0.090 percentage signal change
Standard Deviation 0.137
|
-0.109 percentage signal change
Standard Deviation 0.113
|
-0.066 percentage signal change
Standard Deviation 0.140
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 3.2
|
-0.021 percentage signal change
Standard Deviation 0.139
|
-0.023 percentage signal change
Standard Deviation 0.137
|
-0.022 percentage signal change
Standard Deviation 0.124
|
-0.040 percentage signal change
Standard Deviation 0.111
|
-0.013 percentage signal change
Standard Deviation 0.133
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 4.0
|
0.043 percentage signal change
Standard Deviation 0.142
|
0.034 percentage signal change
Standard Deviation 0.138
|
0.044 percentage signal change
Standard Deviation 0.124
|
0.011 percentage signal change
Standard Deviation 0.119
|
0.046 percentage signal change
Standard Deviation 0.131
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 4.8
|
0.078 percentage signal change
Standard Deviation 0.143
|
0.060 percentage signal change
Standard Deviation 0.136
|
0.079 percentage signal change
Standard Deviation 0.118
|
0.039 percentage signal change
Standard Deviation 0.138
|
0.079 percentage signal change
Standard Deviation 0.134
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 5.6
|
0.085 percentage signal change
Standard Deviation 0.144
|
0.050 percentage signal change
Standard Deviation 0.135
|
0.093 percentage signal change
Standard Deviation 0.118
|
0.049 percentage signal change
Standard Deviation 0.146
|
0.062 percentage signal change
Standard Deviation 0.118
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 8.0
|
0.046 percentage signal change
Standard Deviation 0.129
|
0.033 percentage signal change
Standard Deviation 0.146
|
0.048 percentage signal change
Standard Deviation 0.131
|
0.026 percentage signal change
Standard Deviation 0.131
|
0.026 percentage signal change
Standard Deviation 0.094
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 8.8
|
0.066 percentage signal change
Standard Deviation 0.127
|
0.085 percentage signal change
Standard Deviation 0.150
|
0.073 percentage signal change
Standard Deviation 0.123
|
0.043 percentage signal change
Standard Deviation 0.136
|
0.041 percentage signal change
Standard Deviation 0.093
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 9.6
|
0.090 percentage signal change
Standard Deviation 0.137
|
0.109 percentage signal change
Standard Deviation 0.143
|
0.101 percentage signal change
Standard Deviation 0.115
|
0.077 percentage signal change
Standard Deviation 0.144
|
0.071 percentage signal change
Standard Deviation 0.097
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 10.4
|
0.096 percentage signal change
Standard Deviation 0.143
|
0.125 percentage signal change
Standard Deviation 0.137
|
0.115 percentage signal change
Standard Deviation 0.120
|
0.085 percentage signal change
Standard Deviation 0.135
|
0.079 percentage signal change
Standard Deviation 0.111
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 11.2
|
0.084 percentage signal change
Standard Deviation 0.148
|
0.118 percentage signal change
Standard Deviation 0.131
|
0.097 percentage signal change
Standard Deviation 0.116
|
0.067 percentage signal change
Standard Deviation 0.131
|
0.070 percentage signal change
Standard Deviation 0.110
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 12.0
|
0.060 percentage signal change
Standard Deviation 0.145
|
0.084 percentage signal change
Standard Deviation 0.126
|
0.073 percentage signal change
Standard Deviation 0.120
|
0.052 percentage signal change
Standard Deviation 0.133
|
0.062 percentage signal change
Standard Deviation 0.120
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 12.8
|
0.026 percentage signal change
Standard Deviation 0.163
|
0.053 percentage signal change
Standard Deviation 0.129
|
0.047 percentage signal change
Standard Deviation 0.128
|
0.025 percentage signal change
Standard Deviation 0.123
|
0.033 percentage signal change
Standard Deviation 0.123
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 13.6
|
0.010 percentage signal change
Standard Deviation 0.150
|
0.037 percentage signal change
Standard Deviation 0.121
|
0.046 percentage signal change
Standard Deviation 0.135
|
0.003 percentage signal change
Standard Deviation 0.118
|
0.021 percentage signal change
Standard Deviation 0.128
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 14.4
|
0.042 percentage signal change
Standard Deviation 0.158
|
0.058 percentage signal change
Standard Deviation 0.118
|
0.089 percentage signal change
Standard Deviation 0.151
|
0.033 percentage signal change
Standard Deviation 0.125
|
0.049 percentage signal change
Standard Deviation 0.134
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 15.2
|
0.074 percentage signal change
Standard Deviation 0.169
|
0.095 percentage signal change
Standard Deviation 0.138
|
0.129 percentage signal change
Standard Deviation 0.172
|
0.059 percentage signal change
Standard Deviation 0.148
|
0.086 percentage signal change
Standard Deviation 0.142
|
|
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Second 16.0
|
0.118 percentage signal change
Standard Deviation 0.161
|
0.122 percentage signal change
Standard Deviation 0.148
|
0.172 percentage signal change
Standard Deviation 0.154
|
0.091 percentage signal change
Standard Deviation 0.190
|
0.120 percentage signal change
Standard Deviation 0.144
|
SECONDARY outcome
Timeframe: Up to two hours for each fMRI session.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).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to two hours for each fMRI session.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).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to two hours for each fMRI session.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).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to two hours for each fMRI session.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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to two hours for each fMRI session.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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to two hours for each fMRI session.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).
Outcome measures
Outcome data not reported
Adverse Events
CVL-562 (PF-06412562) 1mg
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
CVL-562 (PF-06412562) 4mg
Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths
CVL-562 (PF-06412562) 15mg
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
CVL-562 (PF-06412562) 25mg
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Adverse Event Prior to Starting Intervention
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
CVL-562 (PF-06412562) 1mg
n=84 participants at risk
All subjects received 1mg CVL-562 (PF-06412562)
|
CVL-562 (PF-06412562) 4mg
n=84 participants at risk
All subjects received 4mg CVL-562 (PF-06412562)
|
CVL-562 (PF-06412562) 15mg
n=84 participants at risk
All subjects received 15mg CVL-562 (PF-06412562)
|
CVL-562 (PF-06412562) 25mg
n=84 participants at risk
All subjects received 25mg CVL-562 (PF-06412562)
|
Placebo
n=84 participants at risk
All subjects received Placebo
|
Adverse Event Prior to Starting Intervention
n=84 participants at risk
Adverse event occurred prior to starting intervention
|
|---|---|---|---|---|---|---|
|
Psychiatric disorders
worsening pyschosis
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
1.2%
1/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Eye disorders
fall and loss of vision in eye
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
1.2%
1/84 • 21 weeks
|
Other adverse events
| Measure |
CVL-562 (PF-06412562) 1mg
n=84 participants at risk
All subjects received 1mg CVL-562 (PF-06412562)
|
CVL-562 (PF-06412562) 4mg
n=84 participants at risk
All subjects received 4mg CVL-562 (PF-06412562)
|
CVL-562 (PF-06412562) 15mg
n=84 participants at risk
All subjects received 15mg CVL-562 (PF-06412562)
|
CVL-562 (PF-06412562) 25mg
n=84 participants at risk
All subjects received 25mg CVL-562 (PF-06412562)
|
Placebo
n=84 participants at risk
All subjects received Placebo
|
Adverse Event Prior to Starting Intervention
n=84 participants at risk
Adverse event occurred prior to starting intervention
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
sleepiness
|
23.8%
20/84 • 21 weeks
|
25.0%
21/84 • 21 weeks
|
34.5%
29/84 • 21 weeks
|
25.0%
21/84 • 21 weeks
|
28.6%
24/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Gastrointestinal disorders
nausea
|
6.0%
5/84 • 21 weeks
|
7.1%
6/84 • 21 weeks
|
19.0%
16/84 • 21 weeks
|
41.7%
35/84 • 21 weeks
|
3.6%
3/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Nervous system disorders
headache
|
9.5%
8/84 • 21 weeks
|
9.5%
8/84 • 21 weeks
|
14.3%
12/84 • 21 weeks
|
16.7%
14/84 • 21 weeks
|
7.1%
6/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
General disorders
low energy
|
9.5%
8/84 • 21 weeks
|
6.0%
5/84 • 21 weeks
|
4.8%
4/84 • 21 weeks
|
13.1%
11/84 • 21 weeks
|
13.1%
11/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Nervous system disorders
light-headedness
|
8.3%
7/84 • 21 weeks
|
8.3%
7/84 • 21 weeks
|
11.9%
10/84 • 21 weeks
|
11.9%
10/84 • 21 weeks
|
8.3%
7/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Psychiatric disorders
anxiety
|
8.3%
7/84 • 21 weeks
|
7.1%
6/84 • 21 weeks
|
4.8%
4/84 • 21 weeks
|
8.3%
7/84 • 21 weeks
|
3.6%
3/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Gastrointestinal disorders
abdominal discomfort
|
3.6%
3/84 • 21 weeks
|
2.4%
2/84 • 21 weeks
|
7.1%
6/84 • 21 weeks
|
4.8%
4/84 • 21 weeks
|
7.1%
6/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
General disorders
vomiting
|
0.00%
0/84 • 21 weeks
|
1.2%
1/84 • 21 weeks
|
3.6%
3/84 • 21 weeks
|
16.7%
14/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Psychiatric disorders
worsened psychosis
|
3.6%
3/84 • 21 weeks
|
2.4%
2/84 • 21 weeks
|
6.0%
5/84 • 21 weeks
|
6.0%
5/84 • 21 weeks
|
4.8%
4/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
|
Nervous system disorders
Back pain
|
0.00%
0/84 • 21 weeks
|
2.4%
2/84 • 21 weeks
|
2.4%
2/84 • 21 weeks
|
1.2%
1/84 • 21 weeks
|
2.4%
2/84 • 21 weeks
|
0.00%
0/84 • 21 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place