A Study To Examine The Safety, Tolerability And Pharmacokinetics Of PF-02545920 In Psychiatrically Stable Subjects With Schizophrenia

Phase 1

Completed

Conditions: Schizophrenia

Interventions: Drug: Placebo
Drug: PF-02545920

Registration Number: NCT01829048

Lead Sponsor: Pfizer

Brief Summary: To evaluate the safety and tolerability of multiple doses of PF 02545920 administered orally to psychiatrically stable subjects with schizophrenia receiving background antipsychotic +/- other adjunctive medication.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Psychiatrically stable subjects with schizophrenia.
Evidence of stable schizophrenia symptomatology greater than or equal to 3 months.
Subjects must be on a stable medication treatment regimen greater than or equal to 2 months, including concomitant psychotropic medications.

Exclusion Criteria

History of seizures or of a condition with risk of seizures.
Subjects who have had electroconvulsive therapy within the 6 months prior to randomization.
Pregnant or nursing females, and females of child bearing potential.

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
PF-02545920	PF-02545920	-

Primary Outcome Measures

Name	Time	Method
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 18 (Cohort 3)	0 hour (predose) on Day 18
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 18 (Cohort 3)	25 minutes (post dose) Day 18
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 18 (Cohort 3)	1 hour 30 minutes (post dose) on Day 18
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 18 (Cohort 3)	5 hours (post dose) on Day 18
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 18 (Cohort 3)	24 hours (post dose) on Day 18
Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10	Day 0 (Baseline) up to Day 10	ESRS-A is a clinician rated scale consisting of 24 items to assess severity of extrapyramidal symptoms for following parameters: parkinsonism (10 items), dystonia (6 items), dyskinesia (6 items) and akathisia (2 items). Each item was scored on a 6-point scale (0=absent, 1=minimal, 2=mild, 3=moderate, 4=severe, 5=extreme). Additionally, 4 Clinical Global Impression of Severity (CGI-S) items were assessed on a 7-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill): CGI-S parkinsonism; CGI-S dystonia; CGI-S dyskinesia; CGI-S akathisia.
Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18	Day 0 (Baseline) up to Day 18	ESRS-A is a clinician rated scale consisting of 24 items to assess severity of extrapyramidal symptoms for following parameters: parkinsonism (10 items), dystonia (6 items), dyskinesia (6 items) and akathisia (2 items). Each item is scored on a 6-point Likert scale (0=absent, 1=minimal, 2=mild, 3=moderate, 4=severe, 5=extreme). Additionally, 4 CGI-S items were assessed on a 7-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill): CGI-S parkinsonism; CGI-S dystonia; CGI-S dyskinesia; CGI-S akathisia.
Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0)	Day 0 (Baseline)	Data relevant to the assessment of suicidality was mapped to the Columbia-Classification Algorithm of Suicide Assessment (C-CASA) event codes. C-SSRS assessed whether participant experienced following: completed suicide (Event code 1), suicide attempt (Event code 2) (Response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (Event code 3) ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), suicidal ideation (Event code 4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Event code 7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior"). Number of participants with "Yes" response for above mentioned categories were assessed.
Number of Participants With Abnormal Neurological Examination Findings (Cohorts 1 and 2)	Day 0 up to Follow-up (any day between Day 17 and 20)	The neurological examination included 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.
Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11	Day 11	Data relevant to the assessment of suicidality was mapped to the C-CASA event codes. C-SSRS assessed whether participant experienced following: completed suicide (Event code 1), Suicide attempt (Event code 2) (Response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (Event code 3) ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), suicidal ideation (Event code 4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Event code 7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior"). Number of participants with "Yes" response for above mentioned categories were assessed.
Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20)	Follow-up (any day between Day 17 and 20)	Data relevant to the assessment of suicidality was mapped to the C-CASA event codes. C-SSRS assessed whether participant experienced following: completed suicide (Event code 1), Suicide attempt (Event code 2) (Response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (Event code 3) ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), suicidal ideation (Event code 4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Event code 7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior"). Number of participants with "Yes" response for above mentioned categories were assessed.
Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0)	Day 0 (Baseline)	Data relevant to the assessment of suicidality was mapped to the C-CASA event codes. C-SSRS assessed whether participant experienced following: Completed suicide (Event code 1), Suicide attempt (Event code 2) (Response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (Event code 3) ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), suicidal ideation (Event code 4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Event code 7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior"). Number of participants with "Yes" response for above mentioned categories were assessed.
Number of Participants With Response to C-SSRS (Cohort 3) at Day 19	Day 19	Data relevant to the assessment of suicidality was mapped to the C-CASA event codes. C-SSRS assessed whether participant experienced following: Completed suicide (Event code 1), Suicide attempt (Event code 2) (Response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (Event code 3) ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), suicidal ideation (Event code 4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Event code 7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior"). Number of participants with "Yes" response for above mentioned categories were assessed.
Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29)	Follow-up (any day between Day 26 and 29)	Data relevant to the assessment of suicidality was mapped to the C-CASA event codes. C-SSRS assessed whether participant experienced following: Completed suicide (Event code 1), Suicide attempt (Event code 2) (Response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (Event code 3) ("Yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), suicidal ideation (Event code 4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Event code 7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior"). Number of participants with "Yes" response for above mentioned categories were assessed.
Number of Participants With Changes Since Screening in Physical Examination (Cohorts 1 and 2)	Screening up to Follow-up (any day between Day 17 and 20)	A complete physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems was performed at Screening. The limited or abbreviated physical examination was focused on general appearance, the respiratory and cardiovascular systems, as well as towards assessment of subject reported symptoms and performed at other time points than Screening.
Number of Participants With Changes Since Screening in Physical Examination (Cohort 3)	Screening up to Follow-up (any day between Day 26 and 29)	A complete physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems was performed at Screening. The limited or abbreviated physical examination was focused on general appearance, the respiratory and cardiovascular systems, as well as towards assessment of subject reported symptoms and performed at other time points than Screening.
Number of Participants With Abnormal Neurological Examination Findings (Cohort 3)	Day 0 up to Follow-up (any day between Day 26 and 29)	The neurological examination included 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Cohorts 1 and 2)	The time receiving the first dose of PF-02545920 or placebo through the last Follow-up (any day between Day 17 and 20)	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to last subject visit that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With TEAEs (Cohort 3)	The time receiving the first dose of PF-02545920/placebo through the last Follow-up (any day between Day 26 and 29)	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to last subject visit that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Abnormal Clinical Laboratory Measurements (Cohorts 1 and 2)	Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20)	The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed.
Number of Participants With Abnormal Clinical Laboratory Measurements (Cohort 3)	Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29)	The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed.
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2)	Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20)	Vital signs included blood pressure (BP; supine and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic \>=30 millimeters of mercury (mm Hg) change from baseline in same posture, systolic \<90 mm Hg; diastolic \>=20 mm Hg change from baseline in same posture, diastolic \<50 mm Hg; 2), pulse rate (supine/sitting): \<40 or greater than (\>) 120 beats per minute (bpm); Standing: \<40 or \>140 bpm.
Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3)	Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29)	Vital signs included BP (supine and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic \>=30 mm Hg change from baseline in same posture, systolic \<90 mm Hg; diastolic \>=20 mm Hg change from baseline in same posture, diastolic \<50 mm Hg; 2), pulse rate (supine/sitting): \<40 or \>120 bpm; Standing: \<40 or \>140 bpm.
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2)	Day 0 (Baseline) up to Day 10	12-lead ECG (triplicate) was performed on Day 0 and 12-lead ECG (singlet) was performed at other time points as specified in timeframe. ECG criteria of potential clinical concern were 1), PR interval: \>=300 milliseconds (msec); \>=25% increase when baseline was greater than (\>) 200 msec; or increase \>=50% when baseline was less than or equal to (\<=) 200 msec; 2), QRS interval: \>=140 msec; \>=50% increase from baseline; 3), corrected QT interval (QTc interval): \>=500 msec, QTc interval using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec(borderline), \>=480 msec (prolonged); absolute change 30 - \<60 (borderline), \>=60 msec (prolonged).
Number of Participants With ECG Data Meeting Criteria of Potential Clinical Concern (Cohort 3)	Screening up to Day 18	12-lead ECG (triplicate)was performed on Day 0 and 12-lead ECG (singlet) was performed at other time points as specified in timeframe. ECG criteria of potential clinical concern were 1), PR interval: \>=300 msec; \>=25% increase when baseline \>200 msec; or increase \>=50% when baseline \<=200 msec; 2), QRS interval: \>=140 msec; \>=50% increase from baseline; 3), QTc interval: \>=500 msec, QTcF interval: absolute value \>=450 - \<480 msec (borderline), \>=480 msec (prolonged); absolute change 30 - \<60 (borderline), \>=60 msec (prolonged).
Sparse Pharmacokinetic (PK) Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 10 (Cohorts 1 and 2)	0 hour (predose) on Day 10
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2)	25 minutes (post dose) on Day 10
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2)	1 hour 30 minutes (post dose) on Day 10
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 10 (Cohorts 1 and 2)	5 hours (post dose) on Day 10
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 10 (Cohorts 1 and 2)	24 hours (post dose) on Day 10