Schizophrenia
Conditions
Keywords
PF-02545920, safety, schizophrenia
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.
Interventions
DRUGPF-02545920
15 mg (2 mg X 2d, 5 mg X 2d, 8 mg X 3 d, then 15 mg) Q12h
DRUGPlacebo
Placebo Q12h
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 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. |
| 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 | — |
| 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 (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. |
| 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 | — |
| 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 | — |
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 6 |
| 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). | 8 |
| Placebo (Cohorts 1 and 2) Participants received placebo-matched to PF-02545920 tablets (Cohort 1 or 2) every 12 hours orally for 10 days. | 7 |
| 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). | 14 |
| Placebo (Cohort 3) Participants received placebo-matched to PF-02545920 tablets (Cohort 3) every 12 hours orally for 18 days. | 2 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | PF-02545920 (Cohort 1) | Total | Placebo (Cohort 3) | PF-02545920 (Cohort 3) | Placebo (Cohorts 1 and 2) | PF-02545920 (Cohort 2) |
|---|---|---|---|---|---|---|
| Age, Customized 18-44 years | 1 participants | 16 participants | 2 participants | 5 participants | 1 participants | 7 participants |
| Age, Customized 45-64 | 5 participants | 21 participants | 0 participants | 9 participants | 6 participants | 1 participants |
| Age, Customized Greater or equal to (>=) 65 | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized less than (<) 18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 34 Participants | 2 Participants | 14 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 5 / 8 | 3 / 7 | 9 / 14 | 1 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 14 | 0 / 2 |
Outcome results
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.
Time frame: Day 0 (Baseline) up to Day 10
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Parkinsonism | -0.2 Units on a scale | Standard Deviation 1.6 |
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Akathisia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Parkinsonism | 0.0 Units on a scale | Standard Deviation 0.63 |
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Akathisia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Akathisia | 0.5 Units on a scale | Standard Deviation 0.93 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Parkinsonism | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Parkinsonism | -0.3 Units on a scale | Standard Deviation 0.46 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Akathisia | 0.1 Units on a scale | Standard Deviation 0.35 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Dyskinesia | -0.1 Units on a scale | Standard Deviation 0.38 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Dystonia | -0.1 Units on a scale | Standard Deviation 0.38 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Parkinsonism | 0.1 Units on a scale | Standard Deviation 1.21 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | ESRS-A Akathisia | 0.0 Units on a scale | Standard Deviation 0 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Dyskinesia | -0.1 Units on a scale | Standard Deviation 0.38 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Dystonia | -0.1 Units on a scale | Standard Deviation 0.38 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Parkinsonism | 0.0 Units on a scale | Standard Deviation 0.58 |
| Placebo (Cohorts 1 and 2) | Change From Baseline in Abbreviated Extrapyramidal Symptom Rating Scale (ESRS-A) Scores (Cohorts 1 and 2) at Day 10 | CGI-S Akathisia | 0.0 Units on a scale | Standard Deviation 0 |
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.
Time frame: Day 0 (Baseline) up to Day 18
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Parkinsonism | 0.3 Units on a scale | Standard Deviation 1.5 |
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Akathisia | 0.6 Units on a scale | Standard Deviation 1.38 |
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Parkinsonism | 0.2 Units on a scale | Standard Deviation 0.58 |
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 1) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Akathisia | 0.3 Units on a scale | Standard Deviation 0.78 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Akathisia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Parkinsonism | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Parkinsonism | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Dyskinesia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | CGI-S Dystonia | 0.0 Units on a scale | Standard Deviation 0 |
| PF-02545920 (Cohort 2) | Change From Baseline in ESRS-A Scores (Cohort 3) at Day 18 | ESRS-A Akathisia | 0.0 Units on a scale | Standard Deviation 0 |
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.
Time frame: Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29)
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Abnormal Clinical Laboratory Measurements (Cohort 3) | 11 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Abnormal Clinical Laboratory Measurements (Cohort 3) | 0 Participants |
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.
Time frame: Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Abnormal Clinical Laboratory Measurements (Cohorts 1 and 2) | 4 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Abnormal Clinical Laboratory Measurements (Cohorts 1 and 2) | 4 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Abnormal Clinical Laboratory Measurements (Cohorts 1 and 2) | 5 Participants |
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.
Time frame: Day 0 up to Follow-up (any day between Day 26 and 29)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Abnormal Neurological Examination Findings (Cohort 3) | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Abnormal Neurological Examination Findings (Cohort 3) | 0 Participants |
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.
Time frame: Day 0 up to Follow-up (any day between Day 17 and 20)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Abnormal Neurological Examination Findings (Cohorts 1 and 2) | 2 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Abnormal Neurological Examination Findings (Cohorts 1 and 2) | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Abnormal Neurological Examination Findings (Cohorts 1 and 2) | 1 Participants |
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.
Time frame: Screening up to Follow-up (any day between Day 26 and 29)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Changes Since Screening in Physical Examination (Cohort 3) | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Changes Since Screening in Physical Examination (Cohort 3) | 0 Participants |
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.
Time frame: Screening up to Follow-up (any day between Day 17 and 20)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Changes Since Screening in Physical Examination (Cohorts 1 and 2) | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Changes Since Screening in Physical Examination (Cohorts 1 and 2) | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Changes Since Screening in Physical Examination (Cohorts 1 and 2) | 0 Participants |
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).
Time frame: Screening up to Day 18
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With ECG Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | 0 participants |
| PF-02545920 (Cohort 2) | Number of Participants With ECG Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | 0 participants |
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).
Time frame: Day 0 (Baseline) up to Day 10
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | 0 Participants |
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.
Time frame: Day 0 (Baseline)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 7 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 7 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 4 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 1 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 3 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to Columbia-Suicide Severity Rating Scale (C-SSRS) (Cohorts 1 and 2) at Baseline (Day 0) | C-CASA Event Code 2 | 0 Participants |
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.
Time frame: Day 0 (Baseline)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Baseline (Day 0) | C-CASA Event Code 4 | 0 Participants |
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.
Time frame: Day 19
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Day 19 | C-CASA Event Code 4 | 0 Participants |
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.
Time frame: Follow-up (any day between Day 26 and 29)
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohort 3) at Follow-up (Any Day Between Day 26 and 29) | C-CASA Event Code 4 | 0 Participants |
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.
Time frame: Day 11
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Participants analyzed indicated number of evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 7 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 7 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 4 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 1 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 3 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Day 11 | C-CASA Event Code 2 | 0 Participants |
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.
Time frame: Follow-up (any day between Day 17 and 20)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 7 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 3 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 1 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 2 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 4 | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 7 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 7 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 4 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 1 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 3 | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Response to C-SSRS (Cohorts 1 and 2) at Follow-up (Any Day Between Day 17 and 20) | C-CASA Event Code 2 | 0 Participants |
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.
Time frame: The time receiving the first dose of PF-02545920/placebo through the last Follow-up (any day between Day 26 and 29)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With TEAEs (Cohort 3) | 9 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With TEAEs (Cohort 3) | 1 Participants |
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.
Time frame: The time receiving the first dose of PF-02545920 or placebo through the last Follow-up (any day between Day 17 and 20)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Cohorts 1 and 2) | 5 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Cohorts 1 and 2) | 5 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Cohorts 1 and 2) | 3 Participants |
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.
Time frame: Day 0 (Baseline) up to Follow-up (any day between Day 26 and 29)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in supine systolic BP >= 30 mm Hg | 2 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in standing systolic BP >= 30 mm Hg | 6 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Increase in supine systolic BP >= 30 mm Hg | 2 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in supine diastolic BP >= 20 mm Hg | 3 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Increase in supine diastolic BP >= 20 mm Hg | 1 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in standing diastolic BP >= 20 mm Hg | 7 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Increase in standing systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in standing diastolic BP >= 20 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Increase in supine systolic BP >= 30 mm Hg | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Increase in standing systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Increase in supine diastolic BP >= 20 mm Hg | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in standing systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in supine diastolic BP >= 20 mm Hg | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohort 3) | Decrease in supine systolic BP >= 30 mm Hg | 0 Participants |
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.
Time frame: Day 0 (Baseline) up to Follow-up (any day between Day 17 and 20)
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Supine systolic BP < 90 mm Hg | 1 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Standing systolic BP < 90 mm Hg | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in supine systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in standing systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in supine diastolic BP >= 20 mm Hg | 2 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in standing diastolic BP >= 20 mm Hg | 1 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in supine systolic BP >= 30 mm Hg | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in standing systolic BP >= 30 mm Hg | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in supine diastolic BP >= 20 mm Hg | 0 Participants |
| PF-02545920 (Cohort 1) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in standing diastolic BP >= 20 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in supine diastolic BP >= 20 mm Hg | 3 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Supine systolic BP < 90 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in standing diastolic BP >= 20 mm Hg | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in supine diastolic BP >= 20 mm Hg | 0 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Standing systolic BP < 90 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in standing diastolic BP >= 20 mm Hg | 2 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in standing systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in supine systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in supine systolic BP >= 30 mm Hg | 1 Participants |
| PF-02545920 (Cohort 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in standing systolic BP >= 30 mm Hg | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in standing systolic BP >= 30 mm Hg | 2 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in standing systolic BP >= 30 mm Hg | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in supine diastolic BP >= 20 mm Hg | 1 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in standing diastolic BP >= 20 mm Hg | 1 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in supine diastolic BP >= 20 mm Hg | 1 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in supine systolic BP >= 30 mm Hg | 1 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Supine systolic BP < 90 mm Hg | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Decrease in standing diastolic BP >= 20 mm Hg | 1 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Standing systolic BP < 90 mm Hg | 0 Participants |
| Placebo (Cohorts 1 and 2) | Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern (Cohorts 1 and 2) | Increase in supine systolic BP >= 30 mm Hg | 1 Participants |
Primary
Sparse Pharmacokinetic (PK) Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 10 (Cohorts 1 and 2)
Time frame: 0 hour (predose) on Day 10
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse Pharmacokinetic (PK) Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 10 (Cohorts 1 and 2) | 45.07 nanogram/milliliter (ng/mL) | Standard Deviation 27.56 |
| PF-02545920 (Cohort 2) | Sparse Pharmacokinetic (PK) Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 10 (Cohorts 1 and 2) | 40.25 nanogram/milliliter (ng/mL) | Standard Deviation 31.465 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 18 (Cohort 3)
Time frame: 0 hour (predose) on Day 18
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 0 Hour (Predose) on Day 18 (Cohort 3) | 42.71 ng/mL | Standard Deviation 24.256 |
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)
Time frame: 1 hour 30 minutes (post dose) on Day 10
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2) | 154.0 ng/mL | Standard Deviation 48.248 |
| PF-02545920 (Cohort 2) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2) | 151.1 ng/mL | Standard Deviation 64.913 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 18 (Cohort 3)
Time frame: 1 hour 30 minutes (post dose) on Day 18
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 1 Hour 30 Minutes (Post Dose) on Day 18 (Cohort 3) | 156.4 ng/mL | Standard Deviation 53.842 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 10 (Cohorts 1 and 2)
Time frame: 24 hours (post dose) on Day 10
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 10 (Cohorts 1 and 2) | 24.16 ng/mL | Standard Deviation 21.032 |
| PF-02545920 (Cohort 2) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 10 (Cohorts 1 and 2) | 21.11 ng/mL | Standard Deviation 21.859 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 18 (Cohort 3)
Time frame: 24 hours (post dose) on Day 18
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 24 Hours (Post Dose) on Day 18 (Cohort 3) | 20.85 ng/mL | Standard Deviation 13.798 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2)
Time frame: 25 minutes (post dose) on Day 10
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2) | 116.8 ng/mL | Standard Deviation 72.996 |
| PF-02545920 (Cohort 2) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 10 (Cohorts 1 and 2) | 138.3 ng/mL | Standard Deviation 106.99 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 18 (Cohort 3)
Time frame: 25 minutes (post dose) Day 18
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 25 Minutes (Post Dose) on Day 18 (Cohort 3) | 156.1 ng/mL | Standard Deviation 92.032 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 10 (Cohorts 1 and 2)
Time frame: 5 hours (post dose) on Day 10
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 10 (Cohorts 1 and 2) | 62.38 ng/mL | Standard Deviation 31.441 |
| PF-02545920 (Cohort 2) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 10 (Cohorts 1 and 2) | 59.15 ng/mL | Standard Deviation 33.294 |
Primary
Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 18 (Cohort 3)
Time frame: 5 hours (post dose) on Day 18
Population: PK concentration population included all enrolled participants treated who had at least 1 measurable concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02545920 (Cohort 1) | Sparse PK Sampling for Population PK Analysis: PF-02545920 Concentration at 5 Hours (Post Dose) on Day 18 (Cohort 3) | 61.30 ng/mL | Standard Deviation 23.764 |