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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-02545920 | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-02545920 | Drug | 15 mg (2 mg X 2d, 5 mg X 2d, 8 mg X 3 d, then 15 mg) Q12h |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at 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. | Day 0 (Baseline) up to Day 10 |
| Change From Baseline in ESRS-A Scores (Cohort 3) at 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. | Day 0 (Baseline) up to Day 18 |
| Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| California Clinical Trials Medical Group | Glendale | California | 91206 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-02545920 (Cohort 1) | Participants received PF-02545920 15 milligram (mg) orally in a titrated manner over 10 days (titration scheme: 2 mg every 12 hours for 2 days, then 5 mg every 12 hours for 2 days, then 8 mg every 12 hours for 3 days, and then 15 mg every 12 hours for 3 days). |
| FG001 | PF-02545920 (Cohort 2) | Participants received PF-02545920 15 mg orally in a titrated manner over 10 days (titration scheme: 5 mg every 12 hours for 2 days, then 10 mg every 12 hours for 2 days, and then 15 mg every 12 hours for 6 days). |
| FG002 | Placebo (Cohorts 1 and 2) | Participants received placebo-matched to PF-02545920 tablets (Cohort 1 or 2) every 12 hours orally for 10 days. |
| FG003 | PF-02545920 (Cohort 3) | Participants received PF-02545920 15 mg orally in a titrated manner over 18 days (titration scheme: 5 mg every 12 hours for 7 days, then 10 mg every 12 hours for 7 days, and then 15 mg every 12 hours for 4 days). |
| FG004 | Placebo (Cohort 3) | Participants received placebo-matched to PF-02545920 tablets (Cohort 3) every 12 hours orally for 18 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety analysis set included all participants who received at least 1 dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-02545920 (Cohort 1) | Participants received PF-02545920 15 mg orally in a titrated manner over 10 days (titration scheme: 2 mg every 12 hours for 2 days, then 5 mg every 12 hours for 2 days, then 8 mg every 12 hours for 3 days, and then 15 mg every 12 hours for 3 days). |
| BG001 | PF-02545920 (Cohort 2) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Mean | Standard Deviation | Units on a scale | Day 0 (Baseline) up to Day 10 |
|
From the time the subject had taken at least 1 dose of study treatment through last subject visit. For serious AEs (SAEs), the time began from the subject provided informed consent through 28 calendar days post last administration of study drug.
The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-02545920 (Cohort 1) | Participants received PF-02545920 15 mg orally in a titrated manner over 10 days (titration scheme: 2 mg every 12 hours for 2 days, then 5 mg every 12 hours for 2 days, then 8 mg every 12 hours for 3 days, and then 15 mg every 12 hours for 3 days). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blepharospasm | Eye disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C545121 | 2-((4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy)methyl)quinoline |
| C423142 | KPNA1 protein, human |
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| PF-02545920 | Drug | 15 mg (5 mg X 2d, 10 mg X 2d, then 15 mg) Q12h |
|
|
| PF-02545920 | Drug | 15 mg (5 mg BID for 7 days 10 mg BID for 7 days, then 15 mg BID for 4 days) Q12h |
|
|
| Placebo | Drug | Placebo Q12h |
|
| Day 0 (Baseline) |
| Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at 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. | Day 11 |
| Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at 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. | Follow-up (any day between Day 17 and 20) |
| Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | 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. | Day 0 (Baseline) |
| Number of Participants With Response to C-SSRS (Cohort 3) at 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. | Day 19 |
| Number of Participants With Response to C-SSRS (Cohort 3) at 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. | Follow-up (any day between Day 26 and 29) |
| Number of Participants With Changes Since Screening in Physical Examination (Cohorts 1 and 2) | 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. | Screening up to Follow-up (any day between Day 17 and 20) |
| Number of Participants With Changes Since Screening in Physical Examination (Cohort 3) | 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. | Screening up to Follow-up (any day between Day 26 and 29) |
| Number of Participants With Abnormal Neurological Examination Findings (Cohorts 1 and 2) | 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. | Day 0 up to Follow-up (any day between Day 17 and 20) |
| Number of Participants With Abnormal Neurological Examination Findings (Cohort 3) | 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. | Day 0 up to Follow-up (any day between Day 26 and 29) |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Cohorts 1 and 2) | 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. | The time receiving the first dose of PF-02545920 or placebo through the last Follow-up (any day between Day 17 and 20) |
| Number of Participants With TEAEs (Cohort 3) | 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. | The time receiving the first dose of PF-02545920/placebo through the last Follow-up (any day between Day 26 and 29) |
| Number of Participants With Abnormal Clinical Laboratory Measurements (Cohorts 1 and 2) | The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed. | Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20) |
| Number of Participants With Abnormal Clinical Laboratory Measurements (Cohort 3) | The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed. | Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29) |
| Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | 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. | Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20) |
| Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | 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. | Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29) |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | 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). | Day 0 (Baseline) up to Day 10 |
| Number of Participants With ECG Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | 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). | Screening up to Day 18 |
| 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 |
| 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 |
Participants received PF-02545920 15 mg orally in a titrated manner over 10 days (titration scheme: 5 mg every 12 hours for 2 days, then 10 mg every 12 hours for 2 days, and then 15 mg every 12 hours for 6 days). |
| BG002 | Placebo (Cohorts 1 and 2) | Participants received placebo-matched to PF-02545920 tablets (Cohort 1 or 2) every 12 hours orally for 10 days. |
| BG003 | PF-02545920 (Cohort 3) | Participants received PF-02545920 15 mg orally in a titrated manner over 18 days (titration scheme: 5 mg every 12 hours for 7 days, then 10 mg every 12 hours for 7 days, and then 15 mg every 12 hours for 4 days). |
| BG004 | Placebo (Cohort 3) | Participants received placebo-matched to PF-02545920 tablets (Cohort 3) every 12 hours orally for 18 days. |
| BG005 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants received PF-02545920 15 mg orally in a titrated manner over 10 days (titration scheme: 2 mg every 12 hours for 2 days, then 5 mg every 12 hours for 2 days, then 8 mg every 12 hours for 3 days, and then 15 mg every 12 hours for 3 days). |
| OG001 | PF-02545920 (Cohort 2) | Participants received PF-02545920 15 mg orally in a titrated manner over 10 days (titration scheme: 5 mg every 12 hours for 2 days, then 10 mg every 12 hours for 2 days, and then 15 mg every 12 hours for 6 days). |
| OG002 | Placebo (Cohorts 1 and 2) | Participants received placebo-matched to PF-02545920 tablets (Cohort 1 or 2) every 12 hours orally for 10 days. |
|
|
| Primary | Change From Baseline in ESRS-A Scores (Cohort 3) at 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. | Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants. | Posted | Mean | Standard Deviation | Units on a scale | Day 0 (Baseline) up to Day 18 |
|
|
|
| Primary | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 (Baseline) |
|
|
|
| Primary | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at 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. | Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants. | Posted | Number | Participants | Day 11 |
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| Primary | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Follow-up (any day between Day 17 and 20) |
|
|
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| Primary | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 (Baseline) |
|
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| Primary | Number of Participants With Response to C-SSRS (Cohort 3) at 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. | Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants. | Posted | Number | Participants | Day 19 |
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| Primary | Number of Participants With Response to C-SSRS (Cohort 3) at 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. | Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants. | Posted | Number | Participants | Follow-up (any day between Day 26 and 29) |
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| Primary | Number of Participants With Changes Since Screening in Physical Examination (Cohorts 1 and 2) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Screening up to Follow-up (any day between Day 17 and 20) |
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| Primary | Number of Participants With Changes Since Screening in Physical Examination (Cohort 3) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Screening up to Follow-up (any day between Day 26 and 29) |
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| Primary | Number of Participants With Abnormal Neurological Examination Findings (Cohorts 1 and 2) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 up to Follow-up (any day between Day 17 and 20) |
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| Primary | Number of Participants With Abnormal Neurological Examination Findings (Cohort 3) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 up to Follow-up (any day between Day 26 and 29) |
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| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Cohorts 1 and 2) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | The time receiving the first dose of PF-02545920 or placebo through the last Follow-up (any day between Day 17 and 20) |
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| Primary | Number of Participants With TEAEs (Cohort 3) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | The time receiving the first dose of PF-02545920/placebo through the last Follow-up (any day between Day 26 and 29) |
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| Primary | Number of Participants With Abnormal Clinical Laboratory Measurements (Cohorts 1 and 2) | The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20) |
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| Primary | Number of Participants With Abnormal Clinical Laboratory Measurements (Cohort 3) | The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed. | Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants. | Posted | Number | Participants | Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29) |
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| Primary | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20) |
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| Primary | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | 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. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29) |
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| Primary | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | 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). | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | Participants | Day 0 (Baseline) up to Day 10 |
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| Primary | Number of Participants With ECG Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | 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). | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | participants | Screening up to Day 18 |
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| Primary | Sparse Pharmacokinetic (PK) Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 10 (Cohorts 1 and 2) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | nanogram/milliliter (ng/mL) | 0 hour (predose) on Day 10 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 25 minutes (post dose) on Day 10 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 1 hour 30 minutes (post dose) on Day 10 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 10 (Cohorts 1 and 2) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 5 hours (post dose) on Day 10 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 10 (Cohorts 1 and 2) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 24 hours (post dose) on Day 10 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 18 (Cohort 3) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 0 hour (predose) on Day 18 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 18 (Cohort 3) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 25 minutes (post dose) Day 18 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 18 (Cohort 3) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 1 hour 30 minutes (post dose) on Day 18 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 18 (Cohort 3) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 5 hours (post dose) on Day 18 |
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| Primary | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 18 (Cohort 3) | PK concentration population included all enrolled participants treated who had at least 1 measurable concentration. | Posted | Mean | Standard Deviation | ng/mL | 24 hours (post dose) on Day 18 |
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| 0 |
| 6 |
| 5 |
| 6 |
| EG001 | PF-02545920 (Cohort 2) | Participants received PF-02545920 15 mg orally in a titrated manner over 10 days (titration scheme: 5 mg every 12 hours for 2 days, then 10 mg every 12 hours for 2 days, and then 15 mg every 12 hours for 6 days). | 0 | 8 | 5 | 8 |
| EG002 | Placebo (Cohorts 1 and 2) | Participants received placebo-matched to PF-02545920 tablets (Cohort 1 or 2) every 12 hours orally for 10 days. | 0 | 7 | 3 | 7 |
| EG003 | PF-02545920 (Cohort 3) | Participants received PF-02545920 15 mg orally in a titrated manner over 18 days (titration scheme: 5 mg every 12 hours for 7 days, then 10 mg every 12 hours for 7 days, and then 15 mg every 12 hours for 4 days). | 0 | 14 | 9 | 14 |
| EG004 | Placebo (Cohort 3) | Participants received placebo-matched to PF-02545920 tablets (Cohort 3) every 12 hours orally for 18 days. | 0 | 2 | 1 | 2 |
| Eye irritation | Eye disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Gait disturbance | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Otitis externa | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Orthostatic heart rate response increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Akathisia | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Cognitive disorder | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Dystonia | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Extrapyramidal disorder | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Oromandibular dystonia | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Abnormal dreams | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Euphoric mood | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Psychotic disorder | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 16.1 | Non-systematic Assessment |
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Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| ESRS-A Dyskinesia |
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| ESRS-A Akathisia |
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| CGI-S Parkinsonism |
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| CGI-S Dystonia |
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| CGI-S Dyskinesia |
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| CGI-S Akathisia |
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| Title | Measurements |
|---|---|
|
| C-CASA Event Code 3 |
|
| C-CASA Event Code 4 |
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| C-CASA Event Code 7 |
|
| Title | Measurements |
|---|---|
|
| C-CASA Event Code 3 |
|
| C-CASA Event Code 4 |
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| C-CASA Event Code 7 |
|
| Title | Measurements |
|---|---|
|
| C-CASA Event Code 3 |
|
| C-CASA Event Code 4 |
|
| C-CASA Event Code 7 |
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| C-CASA Event Code 3 |
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| C-CASA Event Code 4 |
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| C-CASA Event Code 7 |
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| C-CASA Event Code 3 |
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| C-CASA Event Code 4 |
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| C-CASA Event Code 7 |
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| C-CASA Event Code 3 |
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| C-CASA Event Code 4 |
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| C-CASA Event Code 7 |
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| Increase in supine systolic BP >= 30 mm Hg |
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| Increase in standing systolic BP >= 30 mm Hg |
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| Increase in supine diastolic BP >= 20 mm Hg |
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| Increase in standing diastolic BP >= 20 mm Hg |
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| Decrease in supine systolic BP >= 30 mm Hg |
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| Decrease in standing systolic BP >= 30 mm Hg |
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| Decrease in supine diastolic BP >= 20 mm Hg |
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| Decrease in standing diastolic BP >= 20 mm Hg |
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| Increase in supine diastolic BP >= 20 mm Hg |
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| Decrease in supine systolic BP >= 30 mm Hg |
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| Decrease in standing systolic BP >= 30 mm Hg |
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| Decrease in supine diastolic BP >= 20 mm Hg |
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| Decrease in standing diastolic BP >= 20 mm Hg |
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