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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02443740
Recruitment Status : Completed
First Posted : May 14, 2015
Results First Posted : May 17, 2018
Last Update Posted : February 17, 2021
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Basic Science
Condition Healthy
Intervention Drug: BIIB118
Enrollment 32
Recruitment Details  
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.
Arm/Group Title Cohort 1 PF-05251749: Placebo + 30 mg + 250 mg + 500 mg Cohort 1 PF-05251749: 3 mg + Placebo + 250 mg + 500 mg Cohort 1 PF-05251749: 3 mg + 30 mg + Placebo + 500 mg Cohort 1 PF-05251749: 3 mg + 30 mg + 250 mg + Placebo Cohort 2 PF-05251749: Placebo + 100 mg + 500 mg + 1000 mg Cohort 2 PF-05251749: 10 mg + Placebo + 500 mg + 1000 mg Cohort 2 PF-05251749: 10 mg + 100 mg + Placebo + 1000 mg Cohort 2 PF-05251749: 10 mg + 100 mg + 500 mg + Placebo Cohort 3 PF-05251749: 500 mg Cohort 4 PF-05251749: 500 mg Unmilled + 500 mg Milled Cohort 4 PF-05251749: 500 mg Milled + 500 mg Unmilled
Hide Arm/Group Description 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 milligram (mg), 250 mg and 500 mg 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. 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 3 mg, placebo, PF-05251749 250 mg and 500 mg 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. 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 3 mg, 30 mg, placebo and PF-05251749 500 mg 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. 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 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. 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 100 mg, PF-05251749 500 mg, PF-05251749 1000 mg 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. 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 10 mg, PF-05251749 placebo, PF-05251749 500 mg, PF-05251749 1000 mg 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. 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 10 mg, PF-05251749 100 mg, PF-05251749 placebo, PF-05251749 1000 mg 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. 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 10 mg, PF-05251749 100 mg, PF-05251749 500 mg, 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. 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. 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 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. 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 500 mg milled, PF-05251749 500 mg 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.
Period Title: Intervention Period 1 (3 Days)
Started 2 2 2 3 2 4 3 2 6 3 3
Completed 1 2 2 3 2 2 2 2 6 3 3
Not Completed 1 0 0 0 0 2 1 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             1             0             0             0             0             0
Protocol Violation             1             0             0             0             0             0             1             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             1             0             0             0             0             0
Period Title: Washout Period 1 (7 Days)
Started 1 2 2 3 2 2 2 2 0 3 3
Completed 1 2 2 3 2 2 2 2 0 3 3
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Period Title: Intervention Period 2 (3 Days)
Started 1 2 2 3 2 2 2 2 0 3 3
Completed 1 2 2 3 2 2 2 2 0 3 3
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 2 (7 Days)
Started 1 2 2 3 2 2 2 2 0 0 0
Completed 1 2 2 3 2 2 2 2 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Period Title: Intervention Period 3 (3 Days)
Started 1 2 2 3 2 2 2 2 0 0 0
Completed 1 2 2 3 2 2 2 2 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 3 (7 Days)
Started 1 2 2 3 2 2 2 2 0 0 0
Completed 1 2 2 3 2 2 2 2 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Period Title: Intervention Period 4 (3 Days)
Started 1 2 2 3 2 2 2 2 0 0 0
Completed 1 2 2 3 2 2 2 2 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Total
Hide Arm/Group Description 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. 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 9 11 6 6 32
Hide Baseline Analysis Population Description
Analysis population was defined as all participants who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 11 participants 6 participants 6 participants 32 participants
32.7  (10.2) 41.3  (6.3) 44.5  (6.0) 38.5  (11.2) 38.9  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 11 participants 6 participants 6 participants 32 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
9
 100.0%
11
 100.0%
6
 100.0%
6
 100.0%
32
 100.0%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15 6 6 6
Measure Type: Number
Unit of Measure: participants
0 2 0 1 0 0 4 3 3 5 0 1
2.Primary Outcome
Title Number of Participants With Laboratory Abnormalities
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15 6 6 6
Measure Type: Number
Unit of Measure: participants
3 2 1 2 3 3 4 3 6 5 1 0
3.Primary Outcome
Title Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15 6 6 6
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 0 0 0 0 0 0 0
4.Primary Outcome
Title Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15 6 6 6
Measure Type: Number
Unit of Measure: participants
0 0 0 1 0 0 3 2 1 0 0 1
5.Primary Outcome
Title Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15
Mean (Standard Deviation)
Unit of Measure: millimeter
Alertness: Baseline 63.95  (21.656) 83.05  (9.176) 79.12  (21.139) 74.92  (24.371) 82.22  (14.773) 89.98  (7.900) 81.37  (22.535) 87.57  (19.500) 83.47  (14.945)
Alertness: Change at 2 hours postdose 11.48  (15.395) 8.87  (20.227) 8.65  (15.615) 14.62  (23.859) 2.28  (7.327) 4.17  (3.247) 0.30  (9.562) -3.40  (10.744) 7.45  (18.622)
Calmness: Baseline 68.83  (27.518) 82.83  (10.424) 84.67  (13.227) 70.83  (23.962) 73.58  (19.135) 79.92  (21.280) 90.33  (11.206) 82.83  (19.372) 80.10  (23.051)
Calmness: Change at 2 hours postdose 9.08  (14.857) 12.42  (25.305) 5.08  (5.800) 2.33  (26.174) 8.75  (6.594) 5.42  (5.545) 3.33  (7.878) -10.33  (33.673) 8.30  (25.787)
Contentment: Baseline 68.10  (26.737) 83.20  (11.331) 84.83  (11.542) 78.03  (18.151) 85.00  (14.105) 84.63  (18.600) 90.50  (9.294) 89.70  (15.592) 86.09  (16.013)
Contentment: Change at 2 hours postdose 7.57  (14.995) 8.20  (21.017) 5.20  (15.491) 7.40  (29.055) 4.90  (4.688) 1.80  (5.362) -0.43  (8.584) -0.97  (11.598) 5.55  (20.253)
6.Primary Outcome
Title Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2
Hide Description 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: 6 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15
Mean (Standard Deviation)
Unit of Measure: millimeter
Alertness: Change at 6 hours postdose 9.25  (22.935) 16.85  (16.053) 12.72  (15.116) 18.72  (22.991) 3.43  (6.825) -2.50  (18.228) -1.07  (10.708) -1.00  (8.820) 5.93  (25.464)
Calmness: Change at 6 hours postdose 6.67  (7.916) 6.83  (16.549) -0.67  (16.136) 16.00  (13.936) 2.58  (6.829) 8.33  (8.542) -1.58  (16.209) 2.17  (2.658) 8.83  (25.441)
Contentment: Change at 6 hours postdose 7.53  (17.418) 11.60  (19.555) 4.80  (9.728) 12.20  (23.074) 1.20  (4.746) 0.80  (9.955) 0.40  (6.331) 3.03  (9.063) 7.51  (19.539)
7.Primary Outcome
Title Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2
Hide Description 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 3: 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15
Mean (Standard Deviation)
Unit of Measure: millimeter
Alertness: Change at 48 hours postdose 15.83  (15.371) 11.45  (13.703) 15.80  (14.284) 20.92  (19.343) 3.90  (13.966) 6.08  (7.372) 6.12  (6.228) 5.62  (6.576) 9.67  (12.048)
Calmness:Change at 48 hours postdose -0.50  (23.791) 6.17  (26.470) 5.33  (9.983) 8.67  (23.920) 3.00  (5.550) -4.83  (20.966) -11.75  (25.284) 10.00  (18.213) 5.27  (18.547)
Contentment: Change at 48 hours postdose 13.70  (17.876) 10.77  (16.112) 6.87  (19.681) 19.60  (21.045) 4.00  (2.343) 2.87  (3.090) 4.60  (7.859) 4.97  (5.967) 7.56  (11.916)
8.Primary Outcome
Title Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
Parkinsonism: Baseline 0.0  (0.00) 0.3  (0.52) 0.3  (0.52) 0.3  (0.52) 0.2  (0.41) 0.0  (0.00) 0.2  (0.41) 0.2  (0.41) 0.1  (0.35)
Parkinsonism: Change at 2 hours postdose 0.0  (0.00) 0.2  (0.75) -0.3  (0.52) -0.3  (0.52) 0.2  (0.41) 0.0  (0.00) -0.2  (0.41) -0.2  (0.41) 0.0  (0.38)
Dystonia: Baseline 0.0  (0.00) 0.2  (0.41) 0.2  (0.41) 0.2  (0.41) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00) 0.1  (0.26)
Dystonia: Change at 2 hours postdose 0.0  (0.00) 0.0  (0.00) -0.2  (0.41) -0.2  (0.41) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00)
9.Primary Outcome
Title Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2
Hide Description 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: 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
Parkinsonism:48 hours postdose 0.0  (0.00) 0.0  (0.63) 0.0  (0.63) -0.2  (0.41) 0.2  (0.41) 0.0  (0.00) -0.2  (0.41) -0.2  (0.41) -0.1  (0.26)
Dystonia: 48 hours postdose 0.0  (0.00) -0.2  (0.41) -0.2  (0.41) -0.2  (0.41) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00) 0.0  (0.00)
10.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of PF-05251749
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
16.7
(38%)
173.9
(33%)
1725
(39%)
1218
(33%)
60.08
(12%)
893.6
(32%)
3078
(18%)
4582
(35%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-05251749 500 mg (FED), Cohort 2: PF-05251749 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio.
Estimated Value 39.58
Confidence Interval (2-Sided) 90%
30.14 to 51.99
Estimation Comments Values have been back-transformed from the log scale.
11.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram*hour per milliliter (ng*hr/mL)
58.95
(52%)
714.7
(48%)
6542
(46%)
14120
(35%)
281.9
(19%)
3548
(27%)
17520
(23%)
33420
(36%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-05251749 500 mg (FED), Cohort 2: PF-05251749 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 80.60
Confidence Interval (2-Sided) 90%
59.74 to 108.75
Estimation Comments Values have been back-transformed from the log scale.
12.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
67.62
(50%)
729.2
(48%)
6607
(47%)
14350
(35%)
300.8
(19%)
3623
(27%)
17910
(24%)
33990
(36%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: PF-05251749 500 mg (FED), Cohort 2: PF-05251749 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 80.12
Confidence Interval (2-Sided) 90%
58.92 to 108.94
Estimation Comments Values have been back-transformed from the log scale.
13.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6
Median (Full Range)
Unit of Measure: hour
1.00
(0.500 to 1.03)
1.00
(0.500 to 1.50)
1.00
(0.500 to 1.02)
3.00
(0.500 to 8.00)
1.00
(1.00 to 1.50)
1.00
(0.500 to 1.00)
1.25
(1.00 to 2.00)
1.00
(1.00 to 4.00)
14.Secondary Outcome
Title Plasma Decay Half-Life (t1/2) of PF-05251749
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hour
5.255  (2.5047) 8.563  (3.3747) 7.707  (2.3957) 8.400  (1.1415) 8.863  (2.2617) 9.520  (2.6104) 9.513  (2.1843) 8.888  (1.2778)
15.Secondary Outcome
Title Apparent Oral Clearance (CL/F) of PF-05251749
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter per hour (L/hr)
44.38
(50%)
41.18
(48%)
37.87
(47%)
34.87
(35%)
33.25
(19%)
27.60
(27%)
27.90
(24%)
29.45
(36%)
16.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F) of PF-05251749
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1.
Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2.
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter
298.9
(37%)
458.5
(37%)
396.7
(29%)
419.0
(34%)
415.1
(22%)
365.7
(31%)
373.7
(18%)
374.4
(42%)
17.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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 3, as pre-specified in protocol.
Arm/Group Title Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
12600
(22%)
19210
(17%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4: PF-05251749 500 mg Unmilled, Cohort 4: PF-05251749 500 mg Milled
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 65.58
Confidence Interval (2-Sided) 90%
62.18 to 69.16
Estimation Comments Values have been back-transformed from the log scale.
18.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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 3, as pre-specified in protocol.
Arm/Group Title Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
13440
(27%)
19590
(19%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4: PF-05251749 500 mg Unmilled, Cohort 4: PF-05251749 500 mg Milled
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 68.62
Confidence Interval (2-Sided) 90%
63.27 to 74.41
Estimation Comments Values have been back-transformed from the log scale.
19.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
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 3, as pre-specified in protocol.
Arm/Group Title Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1007
(18%)
3385
(11%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4: PF-05251749 500 mg Unmilled, Cohort 4: PF-05251749 500 mg Milled
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio.
Estimated Value 29.76
Confidence Interval (2-Sided) 90%
24.17 to 36.64
Estimation Comments Values have been back-transformed from the log scale.
20.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
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 3, as pre-specified in protocol.
Arm/Group Title Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description:
Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4.
Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
Overall Number of Participants Analyzed 6 6
Median (Full Range)
Unit of Measure: hour
2.50
(1.00 to 6.00)
1.00
(0.500 to 1.00)
21.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) Cohort 3: PF-05251749 500 mg CSF
Hide Arm/Group Description:
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1824
(31%)
10920
(28%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration), Cohort 3: PF-05251749 500 mg CSF
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 16.71
Confidence Interval (2-Sided) 90%
15.35 to 18.18
Estimation Comments Values were back-transformed from the log scale.
22.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) Cohort 3: PF-05251749 500 mg CSF
Hide Arm/Group Description:
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
Limited number of samples did not allow calculation of AUCinf; not analyzed.
23.Secondary Outcome
Title Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749
Hide Description [Not Specified]
Time Frame Predose, 1.5, 2.5, 4, and 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) Cohort 3: PF-05251749 500 mg CSF
Hide Arm/Group Description:
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
354.6
(31%)
2331
(29%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration), Cohort 3: PF-05251749 500 mg CSF
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 15.21
Confidence Interval (2-Sided) 90%
13.29 to 17.42
Estimation Comments Values were back-transformed from the log scale.
24.Secondary Outcome
Title Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749
Hide Description [Not Specified]
Time Frame Predose, 1.5, 2.5, 4, and 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) Cohort 3: PF-05251749 500 mg CSF
Hide Arm/Group Description:
Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose.
Participants received a single oral suspension of PF-05251749 500 mg on Day 1.
Overall Number of Participants Analyzed 6 6
Median (Full Range)
Unit of Measure: hour
1.59
(1.52 to 2.80)
1.37
(1.37 to 4.00)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Hide Arm/Group Description Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4.
All-Cause Mortality
Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/15 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: PF-05251749 3 mg Cohort 1: PF-05251749 30 mg Cohort 1: PF-05251749 250 mg Cohort 1: PF-05251749 500 mg (FED) Cohort 2: PF-05251749 10 mg Cohort 2: PF-05251749 100 mg Cohort 2: PF-05251749 500 mg Cohort 2: PF-05251749 1000 mg Cohort 1-2: Placebo Cohort 3: PF-05251749 500 mg CSF Cohort 4: PF-05251749 500 mg Unmilled Cohort 4: PF-05251749 500 mg Milled
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   2/6 (33.33%)   0/6 (0.00%)   1/6 (16.67%)   0/6 (0.00%)   0/6 (0.00%)   4/6 (66.67%)   3/6 (50.00%)   3/15 (20.00%)   5/6 (83.33%)   0/6 (0.00%)   1/6 (16.67%) 
Cardiac disorders                         
Sinus node dysfunction * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Ventricular extrasystoles * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders                         
Diarrhoea * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Flatulence * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Nausea * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/15 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%) 
Vomiting * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
General disorders                         
Catheter site pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Feeling hot * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Hunger * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Vessel puncture site bruise * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Vessel puncture site pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Infections and infestations                         
Upper respiratory tract infection * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications                         
Contusion * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Post lumbar puncture syndrome * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Procedural headache * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  3/6 (50.00%)  0/6 (0.00%)  0/6 (0.00%) 
Procedural pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Investigations                         
Blood pressure diastolic decreased * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Electrocardiogram QT prolonged * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders                         
Arthralgia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Flank pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Musculoskeletal stiffness * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  3/6 (50.00%)  0/6 (0.00%)  0/6 (0.00%) 
Nervous system disorders                         
Dizziness * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Headache * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Psychiatric disorders                         
Anxiety * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders                         
Sleep apnoea syndrome * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders                         
Cold sweat * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02443740    
Other Study ID Numbers: B8001001
SAD ( Other Identifier: Alias Study Number )
First Submitted: May 1, 2015
First Posted: May 14, 2015
Results First Submitted: October 6, 2016
Results First Posted: May 17, 2018
Last Update Posted: February 17, 2021