A Study To Evaluate The Safety And Efficacy Of PF-04958242 In Subjects With Cognitive Impairment Associated With Schizophrenia (CIAS)

SARA is a clinical scale that is based on a semi--quantitative assessment of cerebellar ataxia on an impairment level and complements the brief neurological examination. The SARA has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test.

C-SSRS responses are mapped to the Columbia Classification Algorithm of Suicide Assessment (C-CASA). C-SSRS assesses whether participant experienced following: completed suicide (Category 1); suicide attempt (Category 2) (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior (Category 3) ("Yes" on "aborted attempt", or "interrupted attempt", or "preparatory acts or behavior"); suicidal ideation (Category 4) ("Yes" on "wish to be dead", or "non-specific active suicidal thoughts", or "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent"); self-injurious behavior, no suicidal intent (Category 7) ("Yes" on "has participant engaged in non-suicidal self-injurious behavior"). Number of participants with "Yes" response for above mentioned categories was to be assessed.

The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (ie, working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB yields scores for individual tests that assess specific cognitive domains as well as a composite score. Scores for the individual tests and the overall composite score for all tests are calculated according to the developers' recommended scoring algorithms. The MCCB neurocognitive score contains all of the tests and domains of the MCCB composite score with the exception of social cognition.

The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (ie, working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB yields scores for individual tests that assess specific cognitive domains as well as a composite score. Scores for the individual tests and the overall composite score for all tests are calculated according to the developers' recommended scoring algorithms.

The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (ie, working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB yields scores for individual tests that assess specific cognitive domains as well as a composite score. Scores for the individual tests and the overall composite score for all tests are calculated according to the developers' recommended scoring algorithms.

The SCI-PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale; 7 items that make up the Negative Scale; and 16 items that make up the General Psychopathology Scale. The sum of the 30 items is defined as the total score.

The SCI--PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale; 7 items that make up the Negative Scale; and 16 items that make up the General Psychopathology Scale. The Subscale scores are the sum of corresponding individual items.

The CGI--S consists of a single 7 point rating score of illness severity. Raters select 1 response based on the following question, "Considering your total clinical experience with this particular population, how mentally ill is your patient at this time?" Scores are: 1=Normal, not ill at all; 2=Borderline mentally ill; 3=Mildly ill; 4=Moderately ill; 5=Markedly ill; 6=Severely ill; or 7=Among the most severely ill participants.

The CGI-I consists of a single 7 point rating score total improvement, regardless of whether or not the change is due entirely to drug treatment. Raters select 1 response based on the following question, "Compared to your patient's condition at the beginning of treatment, how much has your patient changed?" Scores are: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; or 7=Very much worse. For the CGI-I, the participant's condition at the Day 1 (baseline) visit is the criterion for judging improvement at subsequent visits.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All AEs (serious and non-serious) occurring following start of treatment or increasing in severity in any period were to be considered as a treatment emergent AE.

Number of participants with laboratory test abnormalities without regard to baseline abnormality is assessed. Laboratory test parameters include hematology, clinical chemistry, urinalysis, follicle stimulating hormone, urine drug screen, and pregnancy test.

ECG criteria of potential clinical concern: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): greater than or equal to (>=) 140 milliseconds (msec), >=50% increase from baseline; 2) PR interval (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): >=300 msec, >=25% increase when baseline is greater than (>) 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec; 3) QTcF interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected using Fridericia's formula): absolute value of 450 to less than (<) 480 msec, 480 to <500 msec, >=500 msec; an increase from baseline of 30 to <60 msec or >=60 msec.

Vital signs criteria of potential clinical concern: 1) systolic blood pressure <90 millimeters of mercury (mm Hg); 2) change from baseline of systolic blood pressure >=30 mm Hg; 3) diastolic blood pressure <50 mm Hg; 4) change from baseline of diastolic blood pressure >=20 mm Hg; 5) supine pulse rate <40 or >120 beats per minute (bpm); 6) standing pulse rate <40 or >140 bpm.

The extended neurological examination includes observation for cerebellar (intention) tremor and for non-cerebellar tremors (eg, resting or positional), finger nose, heel shin, Romberg, tandem walking, positional and gaze-evoked nystagmus, reflexes, muscle strength, cranial nerves, sensory function of upper and lower extremities. The brief neurological examination includes an assessment of motor and sensory function, cranial nerves, reflexes, non-cerebellar tremor (eg, resting or positional) and cerebellar function. The assessment of cerebellar function is complemented by the Scale for the Assessment and Rating of Ataxia (SARA), a clinical scale based on a semi-quantitative assessment of cerebellar ataxia on an impairment level.

A full physical examination includes head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The brief physical examination is focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms.