Safety, Tolerability and Pharmacokinetics of BIIB118 (PF-05251749)

A Phase 1, Randomized, Double Blind, Placebo Controlled Study To Investigate The Safety, Tolerability, Pharmacokinetics And Relative Bioavailability Of Single Escalating Oral Doses Of Pf-05251749 In Healthy Adult Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02443740

Enrollment

Registered

2015-05-14

Start date

2015-05-31

Completion date

2015-10-31

Last updated

2021-02-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

First in human, Single Ascending Dose Study, Safety and Tolerability, Pharmacokinetics, Plasma, Cerebrospinal Fluid

Brief summary

This is a First in human (FIH) single ascending dose study to evaluate the safety, tolerability and pharmacokinetics (PKs) of BIIB118 following single oral doses in healthy human subjects

Detailed description

This study was previously posted by Pfizer. In March, 2020, sponsorship of the trial was transferred to Biogen.

Interventions

DRUGBIIB118

Single ascending doses of BIIB118 as extemporaneously prepared solution/suspension, once every 2 week in a cross over study: 3 mg, 30 mg, 200 mg, 800 mg and placebo

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

•Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests). Female subjects of non-childbearing potential must meet at least one of the following criteria: 1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state; 2. Have undergone a documented hysterectomy and/or bilateral oophorectomy; 3. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs). * Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. * Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion criteria

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication (whichever is longer). * Screening supine blood pressure \>= 140 mm Hg (systolic) or \>=90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is \>=140 mm Hg (systolic) or \>=90 mm Hg (diastolic), repeat per local standard operating procedures (SOP). If orthostatic changes are present and deemed to be clinically significant by the investigator, Subject can be excluded.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Laboratory Abnormalities	Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3	Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(\<)0.8\lower limit of normal(LLN), MCV,MCH,MCHC,MPV:\<0.9\LLN or \>1.1\upper limit of normal(ULN), platelet:\<0.5\LLN or \>1.75\ULN, white blood cell(WBC):\<0.6\LLNor\>1.5\ULN, lymphocyte,neutrophil,total neutrophil:\<0.8\LLN or \>1.2\ULN,basophil,eosinophil,monocyte:\>1.2\ULN; PTT, PT:\>1.1\ULN,Fibrinogen\<0.75\ULNor\>1.25ULN; total, direct, indirect bilirubin \>1.5\ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,alkaline phosphatase:\> 3.0\ULN,total protein,albumin:\<0.8\LLN or \>1.2\ULN;blood urea nitrogen,creatinine:\>1.3\ULN,uric acid\>1.2\ULN;sodium:\<0.95\LLN or\>1.05\ULN,potassium,chloride, calcium,magnesium,bicarbonate:\<0.9\LLN or \>1.1\ULN, phosphate\<0.8\LLN or \>1.2\ULN; glucose \<0.6\LLN or \>1.5\ULN,creatine kinase\>2.0\ULN;urine(specific gravity\<1.003or\>1.030,pH \<4.5or\>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals\>=1,RBC,WBC \>=20\ULN,bacteria\>20);CSF (WBC\>=6,RBC\>0,Albumin\>35).
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3	Criteria for clinically significant change from baseline in vital signs: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm. Maximum increase or decrease from baseline in supine SBP greater than or equal to (\>=)30 mmHg and maximum increase or decrease from baseline in supine DBP \>=20 mmHg.
Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3	ECG parameters included maximum pulse rate (PR) interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for abnormal ECG: Maximum PR interval \>=300 milliseconds (msec) or \>=25 percent increase when baseline is \>200 msec and \>=50 percent increase when baseline is less than or equal to (=\<) 200 msec; QRS interval \>=140 msec or \>=50 percent increase from baseline (IFB); and QTcF 30\<=change\<60 or change\>=60 msec increase. The number of participants with abnormal ECG findings are reported.
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Baseline, Day 1: 2 hours post dose	The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Baseline, Day 1: 6 hours post dose	The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Baseline, Day 3: 48 hours post dose	The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Baseline, Day 1: 2 hours post dose	ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.
Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Baseline, Day 1: 48 hours post dose	ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.

Secondary

Measure	Time frame	Description
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\/k el), where C last\ was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	—
Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749	Predose, 1.5, 2.5, 4, and 8 hours post dose	—
Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749	Predose, 1.5, 2.5, 4, and 8 hours post dose	AUC (0 -∞) = Area under the CSF concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\/k el), where C last\ was the predicted CSF concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749	Predose, 1.5, 2.5, 4, and 8 hours post dose	—
Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749	Predose, 1.5, 2.5, 4, and 8 hours post dose	Area under the CSF concentration-time profile from time zero to the time of last quantifiable concentration (Clast).
Maximum Observed Plasma Concentration (Cmax) of PF-05251749	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	—
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast ).
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\/k el), where C last\ was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	—
Plasma Decay Half-Life (t1/2) of PF-05251749	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	Terminal elimination half-life (t1/2). It was calculated as dividing the natural logarithm to the base e (Log e)\*2/k el, where k el is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Oral Clearance (CL/F) of PF-05251749	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Volume of Distribution (Vz/F) of PF-05251749	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose	Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast).

Countries

United States

Participant flow

Pre-assignment details

The study consisted of 4 cohorts. Cohort 1 and 2 was a 4 period crossover sequence of PF-05251749 and matching placebo. Cohort 3 was designed to characterize the pharmacokinetic (PK) of PF-05251749 in cerebrospinal fluid (CSF) samples. Cohort 4 was a 2 period crossover sequence of unmilled and milled PF-05251749.

Participants by arm

Arm	Count
Cohort 1 Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: Placebo, PF-05251749 30 mg, 250 mg and 500 mg; PF-05251749 3 mg, placebo, PF-05251749 250 mg and 500 mg; PF-05251749 3 mg, 30 mg, placebo and PF-05251749 500 mg; PF-05251749 3 mg, 30 mg, 250 mg and placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period.	9
Cohort 2 Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 placebo, PF-05251749 100mg, PF-05251749 500mg, PF-05251749 1000mg; PF-05251749 10mg, PF-05251749 placebo, PF-05251749 500mg, PF-05251749 1000mg; PF-05251749 10mg, PF-05251749 100mg, PF-05251749 placebo, PF-05251749 1000mg and PF-05251749 10mg, PF-05251749 100mg, PF-05251749 500mg, PF-05251749 placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.	11
Cohort 3 Participants received a single oral dose of PF-05251749 500 mg suspension on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.	6
Cohort 4 Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500mg unmilled, PF-05251749 500mg milled and PF-05251749 500mg milled, PF-05251749 500mg unmilled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period.	6
Total	32

Withdrawals & dropouts

Period	Reason	FG000	FG005	FG006
Intervention Period 1 (3 Days)	Adverse Event	0	1	0
Intervention Period 1 (3 Days)	Protocol Violation	1	0	1
Intervention Period 1 (3 Days)	Withdrawal by Subject	0	1	0

Baseline characteristics

Characteristic	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Total
Age, Continuous	32.7 years STANDARD_DEVIATION 10.2	41.3 years STANDARD_DEVIATION 6.3	44.5 years STANDARD_DEVIATION 6	38.5 years STANDARD_DEVIATION 11.2	38.9 years STANDARD_DEVIATION 9.2
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	9 Participants	11 Participants	6 Participants	6 Participants	32 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	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	0 / 6	2 / 6	0 / 6	1 / 6	0 / 6	0 / 6	4 / 6	3 / 6	3 / 15	5 / 6	0 / 6	1 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 15	0 / 6	0 / 6	0 / 6

Outcome results

Primary

Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2

The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items \[total range 0 to 100, where each item is ordered so that higher scores indicated more alertness\]), b) contentment (average of 2 items \[total range 0 to 100, where higher scores indicated more contentment\]), and c) calmness (average of 5 items \[total range 0 to 100, where higher scores indicated more calmness\]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.

Time frame: Baseline, Day 1: 2 hours post dose

Population: Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	9.08 millimeter	Standard Deviation 14.857
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	11.48 millimeter	Standard Deviation 15.395
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	7.57 millimeter	Standard Deviation 14.995
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	68.10 millimeter	Standard Deviation 26.737
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	68.83 millimeter	Standard Deviation 27.518
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	63.95 millimeter	Standard Deviation 21.656
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	8.87 millimeter	Standard Deviation 20.227
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	12.42 millimeter	Standard Deviation 25.305
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	83.05 millimeter	Standard Deviation 9.176
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	8.20 millimeter	Standard Deviation 21.017
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	82.83 millimeter	Standard Deviation 10.424
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	83.20 millimeter	Standard Deviation 11.331
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	5.20 millimeter	Standard Deviation 15.491
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	84.83 millimeter	Standard Deviation 11.542
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	84.67 millimeter	Standard Deviation 13.227
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	5.08 millimeter	Standard Deviation 5.8
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	8.65 millimeter	Standard Deviation 15.615
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	79.12 millimeter	Standard Deviation 21.139
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	78.03 millimeter	Standard Deviation 18.151
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	74.92 millimeter	Standard Deviation 24.371
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	14.62 millimeter	Standard Deviation 23.859
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	2.33 millimeter	Standard Deviation 26.174
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	7.40 millimeter	Standard Deviation 29.055
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	70.83 millimeter	Standard Deviation 23.962
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	85.00 millimeter	Standard Deviation 14.105
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	8.75 millimeter	Standard Deviation 6.594
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	73.58 millimeter	Standard Deviation 19.135
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	82.22 millimeter	Standard Deviation 14.773
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	2.28 millimeter	Standard Deviation 7.327
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	4.90 millimeter	Standard Deviation 4.688
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	84.63 millimeter	Standard Deviation 18.6
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	89.98 millimeter	Standard Deviation 7.9
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	4.17 millimeter	Standard Deviation 3.247
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	79.92 millimeter	Standard Deviation 21.28
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	5.42 millimeter	Standard Deviation 5.545
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	1.80 millimeter	Standard Deviation 5.362
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	90.50 millimeter	Standard Deviation 9.294
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	-0.43 millimeter	Standard Deviation 8.584
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	3.33 millimeter	Standard Deviation 7.878
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	81.37 millimeter	Standard Deviation 22.535
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	90.33 millimeter	Standard Deviation 11.206
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	0.30 millimeter	Standard Deviation 9.562
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	-10.33 millimeter	Standard Deviation 33.673
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	82.83 millimeter	Standard Deviation 19.372
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	-3.40 millimeter	Standard Deviation 10.744
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	89.70 millimeter	Standard Deviation 15.592
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	87.57 millimeter	Standard Deviation 19.5
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	-0.97 millimeter	Standard Deviation 11.598
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 2 hours postdose	8.30 millimeter	Standard Deviation 25.787
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Baseline	86.09 millimeter	Standard Deviation 16.013
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 2 hours postdose	5.55 millimeter	Standard Deviation 20.253
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 2 hours postdose	7.45 millimeter	Standard Deviation 18.622
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Calmness: Baseline	80.10 millimeter	Standard Deviation 23.051
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2	Alertness: Baseline	83.47 millimeter	Standard Deviation 14.945

Primary

Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2

Time frame: Baseline, Day 3: 48 hours post dose

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	-0.50 millimeter	Standard Deviation 23.791
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	15.83 millimeter	Standard Deviation 15.371
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	13.70 millimeter	Standard Deviation 17.876
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	10.77 millimeter	Standard Deviation 16.112
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	6.17 millimeter	Standard Deviation 26.47
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	11.45 millimeter	Standard Deviation 13.703
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	5.33 millimeter	Standard Deviation 9.983
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	15.80 millimeter	Standard Deviation 14.284
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	6.87 millimeter	Standard Deviation 19.681
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	8.67 millimeter	Standard Deviation 23.92
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	20.92 millimeter	Standard Deviation 19.343
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	19.60 millimeter	Standard Deviation 21.045
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	4.00 millimeter	Standard Deviation 2.343
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	3.00 millimeter	Standard Deviation 5.55
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	3.90 millimeter	Standard Deviation 13.966
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	6.08 millimeter	Standard Deviation 7.372
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	-4.83 millimeter	Standard Deviation 20.966
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	2.87 millimeter	Standard Deviation 3.09
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	6.12 millimeter	Standard Deviation 6.228
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	-11.75 millimeter	Standard Deviation 25.284
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	4.60 millimeter	Standard Deviation 7.859
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	5.62 millimeter	Standard Deviation 6.576
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	10.00 millimeter	Standard Deviation 18.213
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	4.97 millimeter	Standard Deviation 5.967
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Calmness:Change at 48 hours postdose	5.27 millimeter	Standard Deviation 18.547
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 48 hours postdose	7.56 millimeter	Standard Deviation 11.916
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 48 hours postdose	9.67 millimeter	Standard Deviation 12.048

Primary

Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2

Time frame: Baseline, Day 1: 6 hours post dose

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	9.25 millimeter	Standard Deviation 22.935
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	7.53 millimeter	Standard Deviation 17.418
Cohort 1: PF-05251749 3 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	6.67 millimeter	Standard Deviation 7.916
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	11.60 millimeter	Standard Deviation 19.555
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	16.85 millimeter	Standard Deviation 16.053
Cohort 1: PF-05251749 30 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	6.83 millimeter	Standard Deviation 16.549
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	-0.67 millimeter	Standard Deviation 16.136
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	4.80 millimeter	Standard Deviation 9.728
Cohort 1: PF-05251749 250 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	12.72 millimeter	Standard Deviation 15.116
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	16.00 millimeter	Standard Deviation 13.936
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	18.72 millimeter	Standard Deviation 22.991
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	12.20 millimeter	Standard Deviation 23.074
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	3.43 millimeter	Standard Deviation 6.825
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	1.20 millimeter	Standard Deviation 4.746
Cohort 2: PF-05251749 10 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	2.58 millimeter	Standard Deviation 6.829
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	8.33 millimeter	Standard Deviation 8.542
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	-2.50 millimeter	Standard Deviation 18.228
Cohort 2: PF-05251749 100 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	0.80 millimeter	Standard Deviation 9.955
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	-1.07 millimeter	Standard Deviation 10.708
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	0.40 millimeter	Standard Deviation 6.331
Cohort 2: PF-05251749 500 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	-1.58 millimeter	Standard Deviation 16.209
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	-1.00 millimeter	Standard Deviation 8.82
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	2.17 millimeter	Standard Deviation 2.658
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	3.03 millimeter	Standard Deviation 9.063
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Alertness: Change at 6 hours postdose	5.93 millimeter	Standard Deviation 25.464
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Contentment: Change at 6 hours postdose	7.51 millimeter	Standard Deviation 19.539
Cohort 1-2: Placebo	Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2	Calmness: Change at 6 hours postdose	8.83 millimeter	Standard Deviation 25.441

Primary

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2

ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.

Time frame: Baseline, Day 1: 2 hours post dose

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 1: PF-05251749 3 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 1: PF-05251749 3 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.0 units on a scale	Standard Deviation 0
Cohort 1: PF-05251749 3 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.0 units on a scale	Standard Deviation 0
Cohort 1: PF-05251749 30 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	0.2 units on a scale	Standard Deviation 0.75
Cohort 1: PF-05251749 30 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.2 units on a scale	Standard Deviation 0.41
Cohort 1: PF-05251749 30 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 1: PF-05251749 30 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.3 units on a scale	Standard Deviation 0.52
Cohort 1: PF-05251749 250 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.3 units on a scale	Standard Deviation 0.52
Cohort 1: PF-05251749 250 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 1: PF-05251749 250 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	-0.3 units on a scale	Standard Deviation 0.52
Cohort 1: PF-05251749 250 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.2 units on a scale	Standard Deviation 0.41
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	-0.3 units on a scale	Standard Deviation 0.52
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.3 units on a scale	Standard Deviation 0.52
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.2 units on a scale	Standard Deviation 0.41
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 10 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 10 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 10 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 10 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 100 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 100 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 100 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 100 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 500 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 500 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 500 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 500 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.2 units on a scale	Standard Deviation 0.41
Cohort 1-2: Placebo	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 1-2: Placebo	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Change at 2 hours postdose	0.0 units on a scale	Standard Deviation 0.38
Cohort 1-2: Placebo	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Dystonia: Baseline	0.1 units on a scale	Standard Deviation 0.26
Cohort 1-2: Placebo	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2	Parkinsonism: Baseline	0.1 units on a scale	Standard Deviation 0.35

Primary

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2

Time frame: Baseline, Day 1: 48 hours post dose

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 1: PF-05251749 3 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 1: PF-05251749 30 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 1: PF-05251749 30 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	0.0 units on a scale	Standard Deviation 0.63
Cohort 1: PF-05251749 250 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	0.0 units on a scale	Standard Deviation 0.63
Cohort 1: PF-05251749 250 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 1: PF-05251749 500 mg (FED)	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 10 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 10 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 100 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 100 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 500 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 2: PF-05251749 500 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	-0.2 units on a scale	Standard Deviation 0.41
Cohort 2: PF-05251749 1000 mg	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	0.0 units on a scale	Standard Deviation 0
Cohort 1-2: Placebo	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Parkinsonism:48 hours postdose	-0.1 units on a scale	Standard Deviation 0.26
Cohort 1-2: Placebo	Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2	Dystonia: 48 hours postdose	0.0 units on a scale	Standard Deviation 0

Primary

Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings

ECG parameters included maximum pulse rate (PR) interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for abnormal ECG: Maximum PR interval \>=300 milliseconds (msec) or \>=25 percent increase when baseline is \>200 msec and \>=50 percent increase when baseline is less than or equal to (=\<) 200 msec; QRS interval \>=140 msec or \>=50 percent increase from baseline (IFB); and QTcF 30\<=change\<60 or change\>=60 msec increase. The number of participants with abnormal ECG findings are reported.

Time frame: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3

Population: Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm	Measure	Value (NUMBER)
Cohort 1: PF-05251749 3 mg	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 participants
Cohort 1: PF-05251749 30 mg	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 participants
Cohort 1: PF-05251749 250 mg	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 participants
Cohort 1: PF-05251749 500 mg (FED)	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	1 participants
Cohort 2: PF-05251749 10 mg	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 participants
Cohort 2: PF-05251749 100 mg	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 participants
Cohort 2: PF-05251749 500 mg	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	3 participants
Cohort 2: PF-05251749 1000 mg	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	2 participants
Cohort 1-2: Placebo	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	1 participants
Cohort 3: PF-05251749 500 mg CSF	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 participants
Cohort 4: PF-05251749 500 mg Unmilled	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	0 participants
Cohort 4: PF-05251749 500 mg Milled	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings	1 participants

Primary

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Criteria for clinically significant change from baseline in vital signs: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm. Maximum increase or decrease from baseline in supine SBP greater than or equal to (\>=)30 mmHg and maximum increase or decrease from baseline in supine DBP \>=20 mmHg.

Time frame: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3

Population: Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm	Measure	Value (NUMBER)
Cohort 1: PF-05251749 3 mg	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 1: PF-05251749 30 mg	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 1: PF-05251749 250 mg	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 1: PF-05251749 500 mg (FED)	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 2: PF-05251749 10 mg	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 2: PF-05251749 100 mg	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 2: PF-05251749 500 mg	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 2: PF-05251749 1000 mg	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 1-2: Placebo	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 3: PF-05251749 500 mg CSF	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 4: PF-05251749 500 mg Unmilled	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants
Cohort 4: PF-05251749 500 mg Milled	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 participants

Primary

Number of Participants With Laboratory Abnormalities

Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(\<)0.8\*lower limit of normal(LLN), MCV,MCH,MCHC,MPV:\<0.9\*LLN or \>1.1\*upper limit of normal(ULN), platelet:\<0.5\*LLN or \>1.75\*ULN, white blood cell(WBC):\<0.6\*LLNor\>1.5\*ULN, lymphocyte,neutrophil,total neutrophil:\<0.8\*LLN or \>1.2\*ULN,basophil,eosinophil,monocyte:\>1.2\*ULN; PTT, PT:\>1.1\*ULN,Fibrinogen\<0.75\*ULNor\>1.25ULN; total, direct, indirect bilirubin \>1.5\*ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,alkaline phosphatase:\> 3.0\*ULN,total protein,albumin:\<0.8\*LLN or \>1.2\*ULN;blood urea nitrogen,creatinine:\>1.3\*ULN,uric acid\>1.2\*ULN;sodium:\<0.95\*LLN or\>1.05\*ULN,potassium,chloride, calcium,magnesium,bicarbonate:\<0.9\*LLN or \>1.1\*ULN, phosphate\<0.8\*LLN or \>1.2\*ULN; glucose \<0.6\*LLN or \>1.5\*ULN,creatine kinase\>2.0\*ULN;urine(specific gravity\<1.003or\>1.030,pH \<4.5or\>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals\>=1,RBC,WBC \>=20\*ULN,bacteria\>20);CSF (WBC\>=6,RBC\>0,Albumin\>35).

Time frame: Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3

Population: Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm	Measure	Value (NUMBER)
Cohort 1: PF-05251749 3 mg	Number of Participants With Laboratory Abnormalities	3 participants
Cohort 1: PF-05251749 30 mg	Number of Participants With Laboratory Abnormalities	2 participants
Cohort 1: PF-05251749 250 mg	Number of Participants With Laboratory Abnormalities	1 participants
Cohort 1: PF-05251749 500 mg (FED)	Number of Participants With Laboratory Abnormalities	2 participants
Cohort 2: PF-05251749 10 mg	Number of Participants With Laboratory Abnormalities	3 participants
Cohort 2: PF-05251749 100 mg	Number of Participants With Laboratory Abnormalities	3 participants
Cohort 2: PF-05251749 500 mg	Number of Participants With Laboratory Abnormalities	4 participants
Cohort 2: PF-05251749 1000 mg	Number of Participants With Laboratory Abnormalities	3 participants
Cohort 1-2: Placebo	Number of Participants With Laboratory Abnormalities	6 participants
Cohort 3: PF-05251749 500 mg CSF	Number of Participants With Laboratory Abnormalities	5 participants
Cohort 4: PF-05251749 500 mg Unmilled	Number of Participants With Laboratory Abnormalities	1 participants
Cohort 4: PF-05251749 500 mg Milled	Number of Participants With Laboratory Abnormalities	0 participants

Primary

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Time frame: For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3

Population: Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm	Measure	Value (NUMBER)
Cohort 1: PF-05251749 3 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	0 participants
Cohort 1: PF-05251749 30 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	2 participants
Cohort 1: PF-05251749 250 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	0 participants
Cohort 1: PF-05251749 500 mg (FED)	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	1 participants
Cohort 2: PF-05251749 10 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	0 participants
Cohort 2: PF-05251749 100 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	0 participants
Cohort 2: PF-05251749 500 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	4 participants
Cohort 2: PF-05251749 1000 mg	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	3 participants
Cohort 1-2: Placebo	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	3 participants
Cohort 3: PF-05251749 500 mg CSF	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	5 participants
Cohort 4: PF-05251749 500 mg Unmilled	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	0 participants
Cohort 4: PF-05251749 500 mg Milled	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	1 participants

Secondary

Apparent Oral Clearance (CL/F) of PF-05251749

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Population: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Apparent Oral Clearance (CL/F) of PF-05251749	44.38 liter per hour (L/hr)	Geometric Coefficient of Variation 50
Cohort 1: PF-05251749 30 mg	Apparent Oral Clearance (CL/F) of PF-05251749	41.18 liter per hour (L/hr)	Geometric Coefficient of Variation 48
Cohort 1: PF-05251749 250 mg	Apparent Oral Clearance (CL/F) of PF-05251749	37.87 liter per hour (L/hr)	Geometric Coefficient of Variation 47
Cohort 1: PF-05251749 500 mg (FED)	Apparent Oral Clearance (CL/F) of PF-05251749	34.87 liter per hour (L/hr)	Geometric Coefficient of Variation 35
Cohort 2: PF-05251749 10 mg	Apparent Oral Clearance (CL/F) of PF-05251749	33.25 liter per hour (L/hr)	Geometric Coefficient of Variation 19
Cohort 2: PF-05251749 100 mg	Apparent Oral Clearance (CL/F) of PF-05251749	27.60 liter per hour (L/hr)	Geometric Coefficient of Variation 27
Cohort 2: PF-05251749 500 mg	Apparent Oral Clearance (CL/F) of PF-05251749	27.90 liter per hour (L/hr)	Geometric Coefficient of Variation 24
Cohort 2: PF-05251749 1000 mg	Apparent Oral Clearance (CL/F) of PF-05251749	29.45 liter per hour (L/hr)	Geometric Coefficient of Variation 36

Secondary

Apparent Volume of Distribution (Vz/F) of PF-05251749

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Population: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Apparent Volume of Distribution (Vz/F) of PF-05251749	298.9 Liter	Geometric Coefficient of Variation 37
Cohort 1: PF-05251749 30 mg	Apparent Volume of Distribution (Vz/F) of PF-05251749	458.5 Liter	Geometric Coefficient of Variation 37
Cohort 1: PF-05251749 250 mg	Apparent Volume of Distribution (Vz/F) of PF-05251749	396.7 Liter	Geometric Coefficient of Variation 29
Cohort 1: PF-05251749 500 mg (FED)	Apparent Volume of Distribution (Vz/F) of PF-05251749	419.0 Liter	Geometric Coefficient of Variation 34
Cohort 2: PF-05251749 10 mg	Apparent Volume of Distribution (Vz/F) of PF-05251749	415.1 Liter	Geometric Coefficient of Variation 22
Cohort 2: PF-05251749 100 mg	Apparent Volume of Distribution (Vz/F) of PF-05251749	365.7 Liter	Geometric Coefficient of Variation 31
Cohort 2: PF-05251749 500 mg	Apparent Volume of Distribution (Vz/F) of PF-05251749	373.7 Liter	Geometric Coefficient of Variation 18
Cohort 2: PF-05251749 1000 mg	Apparent Volume of Distribution (Vz/F) of PF-05251749	374.4 Liter	Geometric Coefficient of Variation 42

Secondary

Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749

AUC (0 -∞) = Area under the CSF concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\*/k el), where C last\* was the predicted CSF concentration at the last quantifiable time point estimated from the log-linear regression analysis.

Time frame: Predose, 1.5, 2.5, 4, and 8 hours post dose

Population: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol.

Arm	Measure	Value (GEOMETRIC_MEAN)
Cohort 1: PF-05251749 3 mg	Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749	NA ng*hr/mL
Cohort 1: PF-05251749 30 mg	Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749	NA ng*hr/mL

Secondary

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4

AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last\*/k el), where C last\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4	13440 ng*hr/mL	Geometric Coefficient of Variation 27
Cohort 1: PF-05251749 30 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4	19590 ng*hr/mL	Geometric Coefficient of Variation 19

90% CI: [63.27, 74.41]

Secondary

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Population: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	67.62 ng*hr/mL	Geometric Coefficient of Variation 50
Cohort 1: PF-05251749 30 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	729.2 ng*hr/mL	Geometric Coefficient of Variation 48
Cohort 1: PF-05251749 250 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	6607 ng*hr/mL	Geometric Coefficient of Variation 47
Cohort 1: PF-05251749 500 mg (FED)	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	14350 ng*hr/mL	Geometric Coefficient of Variation 35
Cohort 2: PF-05251749 10 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	300.8 ng*hr/mL	Geometric Coefficient of Variation 19
Cohort 2: PF-05251749 100 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	3623 ng*hr/mL	Geometric Coefficient of Variation 27
Cohort 2: PF-05251749 500 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	17910 ng*hr/mL	Geometric Coefficient of Variation 24
Cohort 2: PF-05251749 1000 mg	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749	33990 ng*hr/mL	Geometric Coefficient of Variation 36

90% CI: [58.92, 108.94]

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749

Area under the CSF concentration-time profile from time zero to the time of last quantifiable concentration (Clast).

Time frame: Predose, 1.5, 2.5, 4, and 8 hours post dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749	1824 ng*hr/mL	Geometric Coefficient of Variation 31
Cohort 1: PF-05251749 30 mg	Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749	10920 ng*hr/mL	Geometric Coefficient of Variation 28

90% CI: [15.35, 18.18]

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4

Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast).

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4	12600 ng*hr/mL	Geometric Coefficient of Variation 22
Cohort 1: PF-05251749 30 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4	19210 ng*hr/mL	Geometric Coefficient of Variation 17

90% CI: [62.18, 69.16]

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749

Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast ).

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Population: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	58.95 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 52
Cohort 1: PF-05251749 30 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	714.7 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 48
Cohort 1: PF-05251749 250 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	6542 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 46
Cohort 1: PF-05251749 500 mg (FED)	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	14120 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 35
Cohort 2: PF-05251749 10 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	281.9 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 19
Cohort 2: PF-05251749 100 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	3548 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 27
Cohort 2: PF-05251749 500 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	17520 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 23
Cohort 2: PF-05251749 1000 mg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749	33420 nanogramhour per milliliter (nghr/mL)	Geometric Coefficient of Variation 36

90% CI: [59.74, 108.75]

Secondary

Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749

Time frame: Predose, 1.5, 2.5, 4, and 8 hours post dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749	354.6 ng/mL	Geometric Coefficient of Variation 31
Cohort 1: PF-05251749 30 mg	Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749	2331 ng/mL	Geometric Coefficient of Variation 29

90% CI: [13.29, 17.42]

Secondary

Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4	1007 ng/mL	Geometric Coefficient of Variation 18
Cohort 1: PF-05251749 30 mg	Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4	3385 ng/mL	Geometric Coefficient of Variation 11

90% CI: [24.17, 36.64]

Secondary

Maximum Observed Plasma Concentration (Cmax) of PF-05251749

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Population: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	16.7 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 38
Cohort 1: PF-05251749 30 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	173.9 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 33
Cohort 1: PF-05251749 250 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	1725 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 39
Cohort 1: PF-05251749 500 mg (FED)	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	1218 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 33
Cohort 2: PF-05251749 10 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	60.08 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 12
Cohort 2: PF-05251749 100 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	893.6 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 32
Cohort 2: PF-05251749 500 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	3078 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 18
Cohort 2: PF-05251749 1000 mg	Maximum Observed Plasma Concentration (Cmax) of PF-05251749	4582 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 35

90% CI: [30.14, 51.99]

Secondary

Plasma Decay Half-Life (t1/2) of PF-05251749

Terminal elimination half-life (t1/2). It was calculated as dividing the natural logarithm to the base e (Log e)\*2/k el, where k el is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Population: The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: PF-05251749 3 mg	Plasma Decay Half-Life (t1/2) of PF-05251749	5.255 hour	Standard Deviation 2.5047
Cohort 1: PF-05251749 30 mg	Plasma Decay Half-Life (t1/2) of PF-05251749	8.563 hour	Standard Deviation 3.3747
Cohort 1: PF-05251749 250 mg	Plasma Decay Half-Life (t1/2) of PF-05251749	7.707 hour	Standard Deviation 2.3957
Cohort 1: PF-05251749 500 mg (FED)	Plasma Decay Half-Life (t1/2) of PF-05251749	8.400 hour	Standard Deviation 1.1415
Cohort 2: PF-05251749 10 mg	Plasma Decay Half-Life (t1/2) of PF-05251749	8.863 hour	Standard Deviation 2.2617
Cohort 2: PF-05251749 100 mg	Plasma Decay Half-Life (t1/2) of PF-05251749	9.520 hour	Standard Deviation 2.6104
Cohort 2: PF-05251749 500 mg	Plasma Decay Half-Life (t1/2) of PF-05251749	9.513 hour	Standard Deviation 2.1843
Cohort 2: PF-05251749 1000 mg	Plasma Decay Half-Life (t1/2) of PF-05251749	8.888 hour	Standard Deviation 1.2778

Secondary

Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749

Time frame: Predose, 1.5, 2.5, 4, and 8 hours post dose

Arm	Measure	Value (MEDIAN)
Cohort 1: PF-05251749 3 mg	Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749	1.59 hour
Cohort 1: PF-05251749 30 mg	Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749	1.37 hour

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Arm	Measure	Value (MEDIAN)
Cohort 1: PF-05251749 3 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4	2.50 hour
Cohort 1: PF-05251749 30 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4	1.00 hour

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749

Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose

Population: The PK concentration analysis set included all enrolled participants who were treated and had at least 1 measurable concentration in at least 1 treatment period.

Arm	Measure	Value (MEDIAN)
Cohort 1: PF-05251749 3 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	1.00 hour
Cohort 1: PF-05251749 30 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	1.00 hour
Cohort 1: PF-05251749 250 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	1.00 hour
Cohort 1: PF-05251749 500 mg (FED)	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	3.00 hour
Cohort 2: PF-05251749 10 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	1.00 hour
Cohort 2: PF-05251749 100 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	1.00 hour
Cohort 2: PF-05251749 500 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	1.25 hour
Cohort 2: PF-05251749 1000 mg	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749	1.00 hour

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Safety, Tolerability and Pharmacokinetics of BIIB118 (PF-05251749)

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2

Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2

Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2

Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Number of Participants With Laboratory Abnormalities

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

Apparent Oral Clearance (CL/F) of PF-05251749

Apparent Volume of Distribution (Vz/F) of PF-05251749

Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749

Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749

Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749

Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4

Maximum Observed Plasma Concentration (Cmax) of PF-05251749

Plasma Decay Half-Life (t1/2) of PF-05251749

Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749