A Study To Examine Safety, Pharmacokinetics, And Pharmacodynamic Of Pf 06412562 In Subjects With Schizophrenia

MRI parameter estimates refer to the 90th percentile Z-statistics across all voxels within the Region of Interest (ROI). This task provided a measure of reward anticipation and reward consummation. One of 3 shapes was presented on the screen (each uniquely associated with gain, loss and neutral) as a cue, and participants were instructed to respond to each cue, using their dominant hand, by pressing in response to a subsequent target that appeared for a variable length of time. Baseline was defined as Day 0 assessment. To be included in analysis participants must have complete Monetary Incentive Delay (MID) data at both Baseline and post-baseline, without excessive head motion. Participants with MID \<40% at baseline were excluded from the analysis and summary statistics. Scores were not bounded by a minimum or maximum range, higher z-score implies a greater motivation of the participant by the prospect of monetary gain than no monetary gain.

Time frame: Baseline, Day 15

Population: PPAS was used,defined as subset of FAS dataset.Criteria for PPAS:1)Received all doses of study treatment to which they were randomized;2)No major protocol deviation;3)Had a baseline measurement and at least 1 post baseline measurement for at least 1 PD endpoint.Overall Number of Participants Analyzed=participants evaluable in this outcome measure.

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. Total score range of this subset ranges from 40 (minimum score) to 60 (maximum score), with higher scores indicating better cognitive function.

Time frame: Baseline, Day 13

Population: Per Protocol Analysis Set (PPAS)subset of Full Analysis Set(FAS).Criteria:1)Received all doses of study treatment to which they randomized2)No major protocol deviation3)Had baseline measurement and at least 1 post baseline measurement for at least 1 PD endpoint.Overall Number of Participants Analyzed=participants evaluable in this outcome measure.

The total number of participants with blood and urine laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.

Time frame: Baseline up to Day 15

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

ECG categorical summarization criteria were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): more than or equal to (\>=) 200 milliseconds (msec); for percent change(PChg), \>=25 percent (%) increase when baseline (b)\>100 msec; or increase \>=50% when b less than or equal to (\<=)100 msec; 2), the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval): \>=300 msec; \>=25percent (%) increase when b \>200 msec; or increase \>=50% when b \<=200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec, \>=480-\<500 msec and \>=500 msec; increase from b \>=30 - \<60 and \>=60 msec

Time frame: Baseline up to 7-10 days after last dose of study drug, up to 26 days

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication.

The C-SSRS was an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. Versions were available for Screening/Baseline and follow-up visits. Post-baseline suicidality was displayed without regard to baseline and as new onset or worsening relative to baseline. A participant was considered to have a new onset of suicidality if the participant reported no ideation and no behavior at the baseline assessment. A participant was considered to have a worsening of suicidality if the participant moved to a lower numbered Columbia Classification Algorithm of Suicide Assessment (C-CASA) category (observed in categories 1-4) than was reported at baseline.

Time frame: Baseline, Days 1,7 and follow-up (7-10 days after last dose of study drug, up to 26 days)

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication

Vital Signs tests included systolic and diastolic blood pressure (BP) and pulse rate of seated supine and standing . Vital signs categorical summarization criteria were 1), supine and standing BP: systolic (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (\<) 90 mm Hg; diastolic BP (DBP) \>=20 mm Hg change from baseline, diastolic \<50 mm Hg; 2), supine and standing pulse rate \<40 or greater than (\>) 120 beats per minute (bpm).

Time frame: Baseline up to 7-10 days after last dose of study drug, up to 26 days

Population: The safety analysis set was used, which defined as all participants who received at least 1 dose of study medication.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any events occurring following start of treatment or increasing in severity were counted as treatment emergent. AEs included both serious and non-serious AEs.

Time frame: Baseline up to 7-10 days after last dose of study drug, up to 26 days

Population: The safety analysis set was used, defined as all participants who received at least 1 dose of study medication.

PF-06412562 plasma concentration for each dose at 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16.

Time frame: 6, and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16

Population: The PK concentration analysis set was defined as all participants randomized and treated who had at least 1 PK concentration. Here, number analyzed signifies the participants evaluable for each time points.

PF-06412562 plasma concentration for each dose at times 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day 16.

Time frame: 6 and 12 hours on Days 1, 7 and 12, as well as 0 hours on Day16

Population: The PK concentration analysis set was defined as all participants randomized and treated who had at least 1 PK concentration. Here, number analyzed signifies the participants evaluable for each time points.