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

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

时间窗: 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.

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

时间窗: 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.

Number of Participants With Laboratory Abnormalities

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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 48 Hours Post Dose in Cohorts 1 and 2

时间窗: 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

时间窗: 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

时间窗: 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.