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Study Evaluating The Safety And Efficacy Of PF-03049423 In Subjects With Ischemic Stroke

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: NCT01208233
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : September 23, 2010
Results First Posted : February 19, 2016
Last Update Posted : February 19, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ischemic Stroke
Interventions Drug: PF-03049423
Other: Placebo
Enrollment 181
Recruitment Details  
Pre-assignment Details A total of 181 participants were assigned to study treatment, 178 of which received study treatment.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description Participants received PF-03049423 1 mg once daily for 90 days. Participants received placebo matched to PF-03049423 1 mg once daily for 90 days. Participants received PF-03049423 3 mg once daily for 90 days. Participants received placebo matched to PF-0304942 3 mg once daily for 90 days. Participants received PF-03049423 6 mg once daily for 90 days. Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Period Title: Overall Study
Started 11 9 11 10 70 67
Completed 6 6 7 9 46 46
Not Completed 5 3 4 1 24 21
Reason Not Completed
Adverse Event             0             1             2             0             3             5
Death             0             0             0             0             3             5
Did not meet entrance criteria             2             1             1             0             1             0
Medication error without adverse event             0             0             0             0             0             1
Study terminated by sponsor             0             0             0             0             10             7
Protocol Violation             0             0             0             0             3             0
Other             2             1             0             0             0             1
Withdrawal by Subject             1             0             1             1             4             2
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo Total
Hide Arm/Group Description Participants received PF-03049423 1 mg once daily for 90 days. Participants received placebo matched to PF-03049423 1 mg once daily for 90 days. Participants received PF-03049423 3 mg once daily for 90 days. Participants received placebo matched to PF-0304942 3 mg once daily for 90 days. Participants received PF-03049423 6 mg once daily for 90 days. Participants received placebo matched to PF-0304942 6 mg once daily for 90 days. Total of all reporting groups
Overall Number of Baseline Participants 11 9 11 10 70 67 178
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) consisted of all randomized participants who took any study medication (active or placebo).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 9 participants 11 participants 10 participants 70 participants 67 participants 178 participants
62.3  (14.3) 64.7  (6.0) 69.8  (8.3) 65.8  (13.4) 64.2  (13.1) 65.6  (11.3) 65.1  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 9 participants 11 participants 10 participants 70 participants 67 participants 178 participants
Female
4
  36.4%
2
  22.2%
7
  63.6%
3
  30.0%
28
  40.0%
26
  38.8%
70
  39.3%
Male
7
  63.6%
7
  77.8%
4
  36.4%
7
  70.0%
42
  60.0%
41
  61.2%
108
  60.7%
1.Primary Outcome
Title Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2)
Hide Description The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. *This endpoint was a primary endpoint for Part 1 (timeframe Days 1 to 14), as data for this timeframe were not reported separately, Part 1 and 2 data were reported together.
Time Frame Day 1 (Baseline) up to Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo). Participants analyzed indicated number of participants evaluated.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 10 10 70 66
Measure Type: Number
Unit of Measure: participants
8 8 10 9 64 56
2.Primary Outcome
Title Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern (Part 1* and 2)
Hide Description Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic BP (SBP) greater than or equal to (>=) 30 or 50 millimeters of mercury (mm Hg) change from grand baseline in same posture, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from grand baseline in same posture, diastolic <50 mm Hg; 2), pulse rate (supine, sitting and standing): <40 or greater than (>) 120 beats per minute (bpm); Standing: <40 or >140 bpm. *This endpoint was a primary endpoint for Part 1 (timeframe Days 1 to 14), as data for this timeframe were not reported separately, Part 1 and 2 data were reported together.
Time Frame Day 1 (Baseline) up to follow-up (28 days after Day 90)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo). n=number of evaluable participants.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: participants
Supine SBP <90 mm Hg, n=11,9,11,10,70,67 0 1 1 0 3 0
Sitting SBP <90 mm Hg, n=10,8,9,5,55,59 0 1 1 0 2 2
Standing SBP <90 mm Hg, n=7,7,9,8,49,48 0 0 0 0 1 1
Supine DBP <50 mm Hg, n=11,9,11,10,70,67 0 0 2 1 6 4
Sitting DBP <50 mm Hg, n=10,8,9,5,55,59 0 0 0 0 3 1
Standing DBP <50 mm Hg, n=7,7,9,8,49,48 0 0 0 1 2 3
Supine pulse rate <40 bpm, n=11,9,11,10,70,67 0 0 0 0 1 0
Supine pulse rate >120 bpm, n=11,9,11,10,70,67 0 0 1 0 5 7
Increase:supine SBP >=30 mm Hg, n=11,9,11,10,70,67 2 3 5 3 13 17
Increase: sitting SBP >=30 mm Hg, n=9,6,9,4,48,44 0 2 2 0 10 9
Increase: standing SBP >=30 mm Hg, n=2,3,3,6,19,22 0 0 0 2 2 1
Increase:supine DBP >=20 mm Hg, n=11,9,11,10,70,67 4 2 5 2 16 22
Increase: sitting DBP >=20 mm Hg, n=9,6,9,4,48,44 3 1 2 2 9 12
Increase: standing DBP >=20 mm Hg, n=2,3,3,6,19,22 0 0 0 2 3 3
Decrease:supine SBP >=30 mm Hg, n=11,9,11,10,70,67 7 6 5 4 37 37
Decrease: sitting SBP >=30 mm Hg, n=9,6,9,4,48,44 3 4 6 2 26 18
Decrease: standing SBP >=30 mm Hg, n=2,3,3,6,19,22 2 2 0 2 10 11
Decrease:supine DBP >=20 mm Hg, n=11,9,11,10,70,67 8 6 6 3 32 26
Decrease: sitting DBP >=20 mm Hg, n=9,6,9,4,48,44 1 4 5 1 23 14
Decrease: standing DBP >=20 mm Hg, n=2,3,3,6,19,22 2 2 1 2 6 11
Decrease:supine SBP >=50 mm Hg, n=11,9,11,10,70,67 2 0 1 2 10 9
Decrease: sitting SBP >=50 mm Hg, n=9,6,9,4,48,44 2 1 3 0 7 6
Decrease: standing SBP >=50 mm Hg, n=2,3,3,6,19,22 1 0 0 0 1 2
Sitting pulse rate <40 bpm, n=1,0,2,0,3,2 0 NA [1]  0 NA [2]  0 0
Standing pulse rate <40 bpm, n=0,0,0,2,1,0 NA [1]  NA [1]  NA [1]  0 0 NA [1] 
Sitting pulse rate >120 bpm, n=1,0,2,0,3,2 0 NA [1]  0 NA [1]  0 0
Standing pulse rate >140 bpm, n=0,0,0,2,1,0 NA [1]  NA [1]  NA [1]  0 0 NA [1] 
[1]
No participants were evaluated.
[2]
No participants were evaluated
3.Primary Outcome
Title Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern (Part 1* and 2)
Hide Description ECG criteria of potential clinical concern were 1), PR interval: >=300 milliseconds (msec); >=25% increase when baseline >200 msec; or increase >=50% when baseline <=200 msec; 2), QRS interval: >=140 msec; >=50% increase from baseline; 3), QT interval: >=500 msec, QTc interval using Fridericia’s formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec, >=500 msec; absolute change 30 - <60, >=60 msec. *This endpoint was a primary endpoint for Part 1 (timeframe Days 1 to 14), as data for this timeframe were not reported separately, Part 1 and 2 data were reported together.
Time Frame Day 1 (Baseline) to Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo). n=number of evaluable participants.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: participants
PR interval >=300 msec, n=11,9,11,10,70,67 0 0 0 0 0 0
QRS interval >=140 msec, n=11,9,11,10,70,67 1 0 1 1 0 1
QT interval >=500 msec, n=11,9,11,10,70,67 0 0 0 0 4 1
QTcF interval 450-480 msec, n=11,9,11,10,70,67 2 3 4 2 14 14
QTcF interval 480-500 msec, n=11,9,11,10,70,67 0 1 0 1 4 3
QTcF interval >=500 msec, n=11,9,11,10,70,67 0 0 1 0 0 1
PR interval increase >=25%/50%, n=10,7,9,9,52,47 0 0 1 0 1 0
QRS interval increase >=50%, n=10,9,11,10,69,66 0 0 0 0 0 1
QTcF increase 30-60 msec, n=10,9,11,10,69,66 2 3 4 2 19 11
QTcF increase >=60 msec, n=10,9,11,10,69,66 0 0 0 1 3 5
4.Primary Outcome
Title Number of Participants With Significant Change in Physical Examination Findings (Part 1* and 2)
Hide Description The complete physical examination included examination of the skin, eyes, ears, throat, neck, cardiac, respiratory, gastrointestinal, and musculoskeletal systems. The limited physical examination included examination of the cardiac, respiratory, gastrointestinal, and musculoskeletal systems. *This endpoint was a primary endpoint for Part 1 (timeframe Days 1 to 14), as data for this timeframe were not reported separately, Part 1 and 2 data were reported together.
Time Frame Day 1 (Baseline) up to Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo). Participants analyzed indicated those who had physical examinations done at both baseline and last visit.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 66
Measure Type: Number
Unit of Measure: participants
1 1 0 0 2 0
5.Primary Outcome
Title Number of Participants With Significant Change in Neurological Examination Findings (Part 1* and 2)
Hide Description The complete neurological examination included an assessment of the motor, sensory, cranial nerves, reflexes, mental status and associated motor functions. The limited neurological exam could examine the same categories of neurologic assessments as the full examination, but would differ by the depth in the examination. The examination was required to be done to the extent needed to assess the participant for any potential changes in neurological status, as determined by the Investigator, but had to always include an assessment of motor, vision and hearing. *This endpoint was a primary endpoint for Part 1 (timeframe Days 1 to 14), as data for this timeframe were not reported separately, Part 1 and 2 data were reported together.
Time Frame Day 1 (Baseline) up to Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo). Participants analyzed indicated those who had neurological examinations done at both baseline and last visit.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 66
Measure Type: Number
Unit of Measure: participants
1 1 0 0 4 0
6.Primary Outcome
Title Number of Participants With Suicidal Behavior and/or Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Part 1* and 2)
Hide Description Data were mapped to Columbia-Classification Algorithm of Suicide Assessment (C-CASA) event codes. C-SSRS assessed if participant experienced: completed suicide (Code 1), suicide attempt (Code 2) (Response of “Yes” on “actual attempt”), preparatory acts toward imminent suicidal behavior (Code 3) (“Yes” on “aborted attempt”, "interrupted attempt”, "preparatory acts or behavior”), suicidal ideation (Code 4) (“Yes” on “wish to be dead”, "non-specific active suicidal thoughts”, "active suicidal ideation with methods without intent to act/some intent to act without specific plan or with specific plan and intent), self-injurious behavior, no suicidal intent (Code 7) (“Yes” on “Has participant engaged in non-suicidal self-injurious behavior”). Number of participants with "Yes" response for any of above mentioned categories was assessed. *This was a primary endpoint for Part 1 (timeframe Days 1 to 14), as data for it were not reported separately, Part 1 and 2 data were reported together.
Time Frame Day 7 (Baseline) up to follow up (28 days after Day 90)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo). n=number of participants who had C-SSRS assessed at that visit.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: participants
Day 7, n=0, 0, 1, 1, 64, 57 NA [1]  NA [1]  0 0 1 2
Day 14, n=0, 0, 1, 1, 59, 53 NA [1]  NA [1]  0 0 1 0
Day 30, n=0, 0, 1, 1, 60, 47 NA [1]  NA [1]  0 0 2 0
Day 60, n=0, 0, 1, 1, 55, 44 NA [1]  NA [1]  0 0 2 0
Day 90, n=0, 0, 1, 1, 61, 53 NA [1]  NA [1]  0 0 1 1
Follow-up, n=0, 0, 1, 1, 59, 51 NA [1]  NA [1]  0 0 0 0
[1]
No participants had C-SSRS assessed.
7.Primary Outcome
Title Percentage of Participants With Modified Rankin Scale (mRS) Less Than or Equal to (<=2) at Day 90 (Part 2)
Hide Description The mRS is a 6-point scale of functional recovery. The scale grades participants as having no symptoms (0), minor symptoms (1), minor handicap (2), moderate handicap (3), moderately severe handicap (4), severe handicap (5), or death (6).
Time Frame Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Inferential Full Analysis Set (I-FAS) consisted of participants within the FAS who were randomized to PF-03049423 maximum tolerated dose (MTD) or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). n=number of participants included for comparison between active drug and placebo.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 68 65
Measure Type: Number
Unit of Measure: percentage of participants
Last Observation Carried Forward (LOCF), n=68, 65 42.6 46.2
Observed Cases (OC), n=51, 52 47.1 50.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4962
Comments [Not Specified]
Method Regression, Logistic
Comments LOCF was used to impute missing data.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.735
Confidence Interval (2-Sided) 80%
0.41 to 1.31
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2517
Comments [Not Specified]
Method Regression, Logistic
Comments The analysis was based on OC.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.561
Confidence Interval (2-Sided) 80%
0.29 to 1.07
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic Hand (Part 2)
Hide Description The B&B test is a measure of manual dexterity. The B&B apparatus consists of a box divided into 2 sections and 1-inch hardwood blocks. The blocks began in the compartment of the test box to the dominant side of the participant. The participant was required to transfer the blocks one at a time to the other side of the box as quickly as possible in 1 minute using the non-paretic hand. The box was then turned so all the blocks were in the same side as the paretic hand. The participant was then required to do the test with his/her paretic hand. The participant was told that if more than 1 block was picked up at a time it was to only count as 1 block. The participant was also told that their fingertips needed to cross the partition for the block to be counted. The performance measure for this task was the number of blocks moved within 1 minute.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Number of participants indicated those participants included for comparison between active drug and placebo.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 21 24
Least Squares Mean (Standard Error)
Unit of Measure: blocks moved per minute
26.881  (3.8667) 26.741  (3.5627)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments Paretic hand
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9716
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.141
Confidence Interval (2-Sided) 80%
-4.972 to 5.254
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.9420
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2)
Hide Description The B&B test is a measure of manual dexterity. The B&B apparatus consists of a box divided into 2 sections and 1-inch hardwood blocks. The blocks began in the compartment of the test box to the dominant side of the participant. The participant was required to transfer the blocks one at a time to the other side of the box as quickly as possible in 1 minute using the non-paretic hand. The box was then turned so all the blocks were in the same side as the paretic hand. The participant was then required to do the test with his/her paretic hand. The participant was told that if more than 1 block was picked up at a time it was to only count as 1 block. The participant was also told that their fingertips needed to cross the partition for the block to be counted. The performance measure for this task was the number of blocks moved within 1 minute.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Number of participants indicated those participants included for comparison between active drug and placebo.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 21 24
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
41.830  (7.7810) 31.041  (7.1284)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments Paretic to non-paretic hand ratio (%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1417
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.789
Confidence Interval (2-Sided) 80%
1.401 to 20.177
Parameter Dispersion
Type: Standard Error of the mean
Value: 7.2392
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic and Non-paretic Hands (Part 2)
Hide Description The Hand Grip Strength Test measures the maximum isometric strength of the hand and forearm muscles. The participant was required to squeeze the dynamometer with maximum isometric effort while sitting with shoulder adducted and neutrally roated, elbow flexed at 90 degrees and the forearm in neutral position and wrist between 0 to 30 degrees dorsiflexion and a 0 to 15 degrees ulnar deviation. The participant performed this task 3 times with each hand, starting with the non-paretic hand. The performance measure for this task was the average score measured in pounds of pressure exerted.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). n=number of participants included for comparison between active drug and placebo.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 68 65
Least Squares Mean (Standard Error)
Unit of Measure: pounds
Paretic Hand, n=26, 26 20.556  (4.1829) 30.886  (3.9964)
Non-Paretic Hand, n=46, 41 12.546  (2.3612) 12.312  (2.5029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments Paretic hand
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0611
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.330
Confidence Interval (2-Sided) 80%
-17.351 to -3.310
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.4241
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments Non-paretic hand
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9433
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.235
Confidence Interval (2-Sided) 80%
-4.011 to 4.480
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.2899
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2)
Hide Description The Hand Grip Strength Test measures the maximum isometric strength of the hand and forearm muscles. The participant was required to squeeze the dynamometer with maximum isometric effort while sitting with shoulder adducted and neutrally roated, elbow flexed at 90 degrees and the forearm in neutral position and wrist between 0 to 30 degrees dorsiflexion and a 0 to 15 degrees ulnar deviation. The participant performed this task 3 times with each hand, starting with the non-paretic hand. The performance measure for this task was the average score measured in pounds of pressure exerted.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Number of participants analyzed indicated those participants included for comparison between active drug and placebo.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
23.949  (5.4499) 36.761  (5.1182)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments Paretic to non-paretic hand ratio (%)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0654
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.812
Confidence Interval (2-Sided) 80%
-21.668 to -3.957
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.8448
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With mRS (0-1) at Day 90 (Part 2)
Hide Description The mRS is a 6-point scale of functional recovery. The scale grades participants as having no symptoms (0), minor symptoms (1), minor handicap (2), moderate handicap (3), moderately severe handicap (4), severe handicap (5), or death (6).
Time Frame Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg).
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 68 65
Measure Type: Number
Unit of Measure: percentage of participants
25.0 24.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments LOCF was used to impute missing data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9510
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.972
Confidence Interval (2-Sided) 80%
0.54 to 1.76
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants With National Institutes of Health Stroke Scale (NIHSS) (0-1) at Day 90 (Part 2)
Hide Description The NIHSS is a graded 11-item neurological examination rating speech and language, cognition, visual field deficits, motor and sensory impairments and ataxia used for the clinical assessment of acute stroke therapy. The maximum total score is 42 in a participant with a severe neurological deficit; the minimum score is 0 in a participant without gross neurological deficits.
Time Frame Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg).
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 68 65
Measure Type: Number
Unit of Measure: percentage of participants
25.0 26.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments LOCF was used to impute missing data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7234
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.854
Confidence Interval (2-Sided) 80%
0.48 to 1.51
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in NIHSS at Day 90 (Part 2)
Hide Description The NIHSS is a graded 11-item neurological examination rating speech and language, cognition, visual field deficits, motor and sensory impairments and ataxia used for the clinical assessment of acute stroke therapy. The maximum total score is 42 in a participant with a severe neurological deficit; the minimum score is 0 in a participant without gross neurological deficits.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Participants analyzed indicated number of participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 49 47
Least Squares Mean (Standard Error)
Unit of Measure: unit on a scale
-6.511  (0.5384) -6.228  (0.5655)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6759
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.283
Confidence Interval (2-Sided) 80%
-1.156 to 0.589
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.6755
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With Barthel Index (BI) >= 95 and BI =100 at Day 90 (Part 2)
Hide Description The BI is an index of independence to score the ability of a participant with a neuromuscular or musculoskeletal disorder to care for him or herself. The index rates a participant’s ability on the following 10 activities: feeding, moving from wheelchair to bed, personal toilet, getting on and off toilet, bathing self, walking on level surface, ascending and descending stairs, dressing, controlling bowels and controlling bladder. The maximum total score is 100 in a participant without functional impairment; the minimum score is 0 in a participant with major functional impairment.
Time Frame Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg).
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 68 65
Measure Type: Number
Unit of Measure: percentage of participants
BI >=95 47.1 40.0
BI=100 42.6 35.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments BI >=95, LOCF was used to impute missing data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4213
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.433
Confidence Interval (2-Sided) 80%
0.81 to 2.54
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments BI=100, LOCF was used to impute missing data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2760
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.651
Confidence Interval (2-Sided) 80%
0.92 to 2.98
Estimation Comments [Not Specified]
16.Secondary Outcome
Title BI at Day 90 (Part 2)
Hide Description The BI is an index of independence to score the ability of a participant with a neuromuscular or musculoskeletal disorder to care for him or herself. The index rates a participant’s ability on the following 10 activities: feeding, moving from wheelchair to bed, personal toilet, getting on and off toilet, bathing self, walking on level surface, ascending and descending stairs, dressing, controlling bowels and controlling bladder. The maximum total score is 100 in a participant without functional impairment; the minimum score is 0 in a participant with major functional impairment.
Time Frame Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Participants analyzed indicated number of participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 49 47
Least Squares Mean (Standard Error)
Unit of Measure: unit on a scale
79.151  (3.6248) 73.552  (3.8471)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2118
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.599
Confidence Interval (2-Sided) 80%
-0.150 to 11.348
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.4547
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Domains of Interest: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding Sub Test at Day 90 (Part 2)
Hide Description The test uses a reference key, the participant had 90 seconds to pair specific numbers with given geometric figures. Responses could be written or oral. The performance measure for this task was the total number of correct responses.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Participants analyzed indicated number of participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 33 28
Least Squares Mean (Standard Error)
Unit of Measure: correct responses
13.748  (1.5321) 12.686  (1.6282)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5541
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.062
Confidence Interval (2-Sided) 80%
-1.252 to 3.375
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.7844
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Domains of Interest: Change From Baseline in RBANS Naming Sub Test at Day 90 (Part 2)
Hide Description This test requires the participant to name 10 objects drawn in ink. The tester asked the participant to identify the picture. The participant had 20 seconds to respond to each picture presented. The performance measure was the number of objects named correctly.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Participants analyzed indicated number of participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 41 37
Least Squares Mean (Standard Error)
Unit of Measure: objects named correctly
0.989  (0.3676) 1.324  (0.3666)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4260
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.334
Confidence Interval (2-Sided) 80%
-0.874 to 0.205
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4178
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Domains of Interest: Change From Baseline in Line Cancellation Test [(L+R)/28 × 100%, (L/14) × 100%, (R/14) × 100%)] at Day 90 (Part 2)
Hide Description The participant was presented with a page that had lines placed across the page. The participant was required to cross out all the lines on the page using their non-paretic hand after the tester had demonstrated what was required by crossing out the center line. The performance measure for this task was the total number of omissions made expressed as a percentage of the total number of items in the test. The test contains 4 variables: (L+R)/28 × 100%, (L/14) × 100%, (R/14) × 100%, and (L-R)/(L+R), where L = number of lines crossed on the left side of the paper; R = number of lines crossed on the right side of the paper.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). n=number of participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 68 65
Least Squares Mean (Standard Error)
Unit of Measure: change in percentage of lines crossed
(L+R)/28 × 100%, n=39, 35 19.459  (4.4433) 16.983  (4.4551)
(L/14) × 100%, n=39, 35 22.824  (5.6691) 18.950  (5.6639)
(R/14) × 100%, n=39, 35 16.481  (4.3564) 15.431  (4.3647)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments (L+R)/28 × 100%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6500
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.477
Confidence Interval (2-Sided) 80%
-4.547 to 9.500
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.4394
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments (L/14) × 100%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5671
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.874
Confidence Interval (2-Sided) 80%
-4.834 to 12.583
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.7431
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments (R/14) × 100%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8430
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.049
Confidence Interval (2-Sided) 80%
-5.771 to 7.870
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.2816
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Domains of Interest: Change From Baseline in Line Cancellation Test at Day 90 [(L-R)/(L+R)] (Part 2)
Hide Description The participant was presented with a page that had lines placed across the page. The participant was required to cross out all the lines on the page using their non-paretic hand after the tester had demonstrated what was required by crossing out the center line. The performance measure for this task was the total number of omissions made expressed as a percentage of the total number of items in the test. The test contains 4 variables: (L+R)/28 × 100%, (L/14) × 100%, (R/14) × 100%, and (L-R)/(L+R), where L = number of lines crossed on the left side of the paper; R = number of lines crossed on the right side of the paper.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Number of participants analyzed indicated participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 39 34
Least Squares Mean (Standard Error)
Unit of Measure: change in ratio
0.083  (0.0620) -0.023  (0.0625)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments (L R)/(L+R)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1512
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.106
Confidence Interval (2-Sided) 80%
0.011 to 0.201
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0733
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Domains of Interest: Change From Baseline in Recognition Memory Test at Day 90 (Part 2)
Hide Description This test assesses the ability to recognize pictures of objects. The participant was presented a series of pictures, a subset of which were the objects presented in the RBANS Naming Sub Test. After each picture was presented, the participant indicated either manually (ie, affirmative head nod) or verbally whether the picture was seen previously. The participant was given 5 seconds per picture to respond. The performance measure for this task was the total number of pictures correctly identified.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Participants analyzed indicated number of participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 44 37
Least Squares Mean (Standard Error)
Unit of Measure: pictures correctly identified
-1.135  (0.4743) 0.144  (0.4797)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0128
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.279
Confidence Interval (2-Sided) 80%
-1.929 to -0.629
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5041
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Gait Velocity Test at Day 90 (Part 2)
Hide Description The 10-meter walk test requires a 20 meter straight path, with 5 meters for acceleration, 10 meters for steady state walking, and 5 meters for deceleration. Markers were placed at the 5 and 15 meter positions along the path. The participant began to walk “at a comfortable pace” at 1 end of the path, and continued walking until he/she reached the other end. The rater used a stopwatch to determine how much time it took for the participant to traverse the 10 meter center of the path, starting the stopwatch as soon as the participant’s limb crossed the first marker and stopping the stopwatch as soon as the participant’s limb crossed the second marker.
Time Frame Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Participants analyzed indicated number of participants included for comparison between active drug and placebo for this outcome measure.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 41 36
Least Squares Mean (Standard Error)
Unit of Measure: meters/second (m/s)
1.064  (0.1040) 0.975  (0.1128)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4713
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.089
Confidence Interval (2-Sided) 80%
-0.070 to 0.248
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1226
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Plasma Concentrations of PF-03049423 (Part 1 and 2)
Hide Description [Not Specified]
Time Frame Days 1, 2, 7, 14, 30, 60 and 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK concentration population included all participants who were treated with PF-03049423 who had at least 1 measurable concentration. n=participants with concentration above lower limit of quantification at the corresponding sampling time.
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 2: PF-03049423 3 mg Cohort 3: PF-03049423 6 mg
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 11 70
Mean (Standard Deviation)
Unit of Measure: nanogram/milliliter (ng/mL)
Day 1 (0 hour predose), n=0, 1, 3 NA [1]   (NA) 0.05245  (0.17397) 1.420  (11.591)
Day 1 (1 hour post dose), n=11, 10, 63 5.825  (4.3514) 17.50  (12.814) 46.76  (36.153)
Day 1 (2 hours post dose), n=11, 11, 61 7.063  (3.2729) 30.18  (11.313) 58.19  (32.837)
Day 1 (8 hours post dose), n=11, 11, 68 7.361  (2.4032) 25.39  (8.6644) 52.47  (23.250)
Day 2 (0 hour, predose), n=11, 11, 67 4.521  (1.5265) 18.05  (4.7834) 32.07  (13.776)
Day 7 (0 hour, post dose), n=9, 7, 64 8.601  (2.9609) 27.79  (7.6945) 53.08  (30.237)
Day 7 (1 hour post dose), n=0, 1, 59 NA [2]   (NA) 51.80 [3]   (NA) 115.9  (65.329)
Day 7 (2 hours post dose), n=0, 1, 59 NA [2]   (NA) 58.10 [3]   (NA) 126.3  (57.759)
Day 7 (6 hours post dose), n=0, 1, 61 NA [2]   (NA) 51.10 [3]   (NA) 103.8  (41.090)
Day 14 (0 hour predose), n=10, 8, 59 7.805  (2.9278) 31.13  (9.8243) 53.10  (28.085)
Day 14 (1 hour post dose), n=9, 7, 0 16.47  (7.1782) 76.71  (32.657) NA [2]   (NA)
Day 14 (2 hours post dose), n=9, 6, 0 17.06  (7.3799) 70.37  (14.795) NA [2]   (NA)
Day 14 (6 [cohort 3:4] hours post dose), n=9,7,31 17.57  (4.1614) 58.36  (11.720) 118.2  (41.967)
Day 30 (0 hour predose), n=6, 6, 58 5.339  (3.5712) 29.68  (11.015) 50.77  (31.473)
Day 30 (4 hours post dose), n=2, 5, 25 11.55  (2.6234) 57.08  (13.990) 96.27  (49.929)
Day 60 (0 hour predose), n=6, 6, 53 6.360  (3.1028) 24.55  (5.8206) 49.37  (33.747)
Day 60 (4 hours post dose), n=2, 5, 27 13.25  (0.7778) 47.86  (7.3296) 112.1  (58.560)
Day 90 (0 hour predose), n=5, 6, 45 5.252  (1.5161) 29.18  (15.909) 47.02  (24.065)
Day 90 (4 hours post dose), n=2, 5, 20 12.80  (0.000) 49.40  (13.962) 82.69  (29.005)
[1]
No participants had concentration above lower limit quantification.
[2]
No samples were collected.
[3]
1 participant had concentration above lower limit of quantification, SD cannot be calculated.
24.Secondary Outcome
Title Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Non-paretic Hand (Part 2)
Hide Description The B&B test is a measure of manual dexterity. The B&B apparatus consists of a box divided into 2 sections and 1-inch hardwood blocks. The blocks began in the compartment of the test box to the dominant side of the participant. The participant was required to transfer the blocks one at a time to the other side of the box as quickly as possible in 1 minute using the non-paretic hand. The box was then turned so all the blocks were in the same side as the paretic hand. The participant was then required to do the test with his/her paretic hand. The participant was told that if more than 1 block was picked up at a time it was to only count as 1 block. The participant was also told that their fingertips needed to cross the partition for the block to be counted. The performance measure for this task was the number of blocks moved within 1 minute.
Time Frame Day 1 (Baseline), Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The I-FAS consisted of participants within the FAS who were randomized to PF-03049423 MTD or highest dose (6 mg) group or the placebo group that was in the same cohort as the MTD or highest dose (6 mg). Number of participants indicated those participants included for comparison between active drug and placebo.
Arm/Group Title Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 45 41
Least Squares Mean (Standard Error)
Unit of Measure: blocks moved per minute
17.797  (2.1676) 18.313  (2.2407)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 3: PF-03049423 6 mg, Cohort 3: Placebo
Comments Non-paretic hand
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8501
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.516
Confidence Interval (2-Sided) 80%
-4.026 to 2.995
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.7201
Estimation Comments [Not Specified]
25.Other Pre-specified Outcome
Title All-cause Mortality (Part 2)
Hide Description Deaths regardless causality were reported.
Time Frame The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo).
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: Number of participants
0 0 0 0 6 7
26.Other Pre-specified Outcome
Title Mortality Directly Related to Stroke (Part 2)
Hide Description Deaths caused by stroke were reported.
Time Frame The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo).
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: Number of participants
0 0 0 0 3 0
27.Other Pre-specified Outcome
Title Number of Participants With Neuro-worsening (Part 2)
Hide Description NIHSS change of 4 points or greater.
Time Frame Day 1 (Baseline) up to Day 90
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo).
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: Number of participants
NA [1]  NA [1]  NA [1]  NA [1]  NA [1]  NA [1] 
[1]
No data were reported separately for this outcome measure, which was instead included in routine clinical review of NIHSS data.
28.Other Pre-specified Outcome
Title Number of Participants With SBP <100 mm Hg or SBP Decline >=30 mm Hg From Immediate Pre-dose Measurement, With or Without Neuro-worsening (Defined as an NIHSS Increase of 4 Points or Greater) Within 2 Hours Post-dose (Part 2)
Hide Description [Not Specified]
Time Frame Day 1 (Baseline) up to Day 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo).
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: Number of participants
NA [1]  NA [1]  NA [1]  NA [1]  NA [1]  NA [1] 
[1]
No data were reported separately for this outcome measure, which was instead included in routine clinical review of BP data.
29.Other Pre-specified Outcome
Title Treatment-emergent Adverse Events (AEs) Resulting in Discontinuation of Study Drug (Part 2)
Hide Description An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame Day 1 (Baseline) up to follow-up (28 days after Day 90)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized participants who took any study medication (active or placebo).
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description:
Participants received PF-03049423 1 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 1 mg once daily for 90 days.
Participants received PF-03049423 3 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 3 mg once daily for 90 days.
Participants received PF-03049423 6 mg once daily for 90 days.
Participants received placebo matched to PF-03049423 6 mg once daily for 90 days.
Overall Number of Participants Analyzed 11 9 11 10 70 67
Measure Type: Number
Unit of Measure: Number of participants
0 1 2 0 3 5
Time Frame From the time the subject had taken at least 1 dose of study treatment through last subject visit. For SAEs, the time began from the subject provided informed consent through 28 calendar days post last administration of investigational product.
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Hide Arm/Group Description Participants received PF-03049423 1 mg once daily for 90 days. Participants received placebo matched to PF-03049423 1 mg once daily for 90 days. Participants received PF-03049423 3 mg once daily for 90 days. Participants received placebo matched to PF-0304942 3 mg once daily for 90 days. Participants received PF-03049423 6 mg once daily for 90 days. Participants received placebo matched to PF-0304942 6 mg once daily for 90 days.
All-Cause Mortality
Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/11 (18.18%)   1/9 (11.11%)   3/11 (27.27%)   1/10 (10.00%)   15/70 (21.43%)   18/67 (26.87%) 
Blood and lymphatic system disorders             
Anaemia * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Cardiac disorders             
Acute myocardial infarction * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  2/67 (2.99%) 
Angina pectoris * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Atrial fibrillation * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  1/67 (1.49%) 
Cardiac arrest * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Cardiac failure * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Cardiac failure congestive * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Myocardial infarction * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Gastrointestinal disorders             
Gastrointestinal haemorrhage * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  1/67 (1.49%) 
Haematochezia * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Ileus paralytic * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
Intestinal obstruction * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
General disorders             
Condition aggravated * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Death * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Hepatobiliary disorders             
Cholangitis * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Infections and infestations             
Pneumonia * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Sepsis * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  1/67 (1.49%) 
Urinary tract infection * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  2/67 (2.99%) 
Urosepsis * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Injury, poisoning and procedural complications             
Concussion * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Fall * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Femur fracture * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Radius fracture * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Investigations             
Electrocardiogram ST-T change * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Hepatic enzyme increased * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Metabolism and nutrition disorders             
Hyperglycaemia * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Metastases to bone * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Nervous system disorders             
Brain oedema * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Cerebral haemorrhage * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Cerebral infarction * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Cerebrovascular accident * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  1/67 (1.49%) 
Epilepsy * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  2/67 (2.99%) 
Haemorrhage intracranial * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Ischaemic cerebral infarction * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Ischaemic stroke * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/70 (1.43%)  0/67 (0.00%) 
Subarachnoid haemorrhage * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Psychiatric disorders             
Disorientation * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Renal and urinary disorders             
Haematuria * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Respiratory, thoracic and mediastinal disorders             
Asphyxia * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Pneumonia aspiration * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  2/67 (2.99%) 
Pulmonary embolism * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  3/70 (4.29%)  0/67 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: PF-03049423 1 mg Cohort 1: Placebo Cohort 2: PF-03049423 3 mg Cohort 2: Placebo Cohort 3: PF-03049423 6 mg Cohort 3: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/11 (90.91%)   7/9 (77.78%)   7/11 (63.64%)   9/10 (90.00%)   50/70 (71.43%)   47/67 (70.15%) 
Blood and lymphatic system disorders             
Anaemia * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  4/70 (5.71%)  3/67 (4.48%) 
Leukocytosis * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Neutrophilia * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Thrombocytopenia * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Cardiac disorders             
Atrial fibrillation * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  2/70 (2.86%)  1/67 (1.49%) 
Bradycardia * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  2/70 (2.86%)  1/67 (1.49%) 
Coronary artery occlusion * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Supraventricular extrasystoles * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Congenital, familial and genetic disorders             
Atrial septal defect * 1  0/11 (0.00%)  2/9 (22.22%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  2/67 (2.99%) 
Ear and labyrinth disorders             
Vertigo * 1  1/11 (9.09%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  2/70 (2.86%)  0/67 (0.00%) 
Eye disorders             
Conjunctival hyperaemia * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/70 (1.43%)  0/67 (0.00%) 
Eye disorder * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
Gastrointestinal disorders             
Abdominal distension * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Abdominal pain upper * 1  1/11 (9.09%)  1/9 (11.11%)  0/11 (0.00%)  1/10 (10.00%)  2/70 (2.86%)  1/67 (1.49%) 
Constipation * 1  0/11 (0.00%)  1/9 (11.11%)  1/11 (9.09%)  1/10 (10.00%)  8/70 (11.43%)  14/67 (20.90%) 
Diarrhoea * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  9/70 (12.86%)  10/67 (14.93%) 
Dyspepsia * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  1/10 (10.00%)  1/70 (1.43%)  3/67 (4.48%) 
Gastritis * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Nausea * 1  1/11 (9.09%)  2/9 (22.22%)  1/11 (9.09%)  0/10 (0.00%)  2/70 (2.86%)  4/67 (5.97%) 
Vomiting * 1  0/11 (0.00%)  0/9 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  1/70 (1.43%)  4/67 (5.97%) 
General disorders             
Face oedema * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Feeling cold * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Oedema peripheral * 1  0/11 (0.00%)  0/9 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  3/70 (4.29%)  3/67 (4.48%) 
Pyrexia * 1  1/11 (9.09%)  0/9 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  7/70 (10.00%)  6/67 (8.96%) 
Infections and infestations             
Genitourinary tract infection * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Herpes zoster * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Upper respiratory tract infection * 1  1/11 (9.09%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  3/70 (4.29%)  2/67 (2.99%) 
Urinary tract infection * 1  1/11 (9.09%)  0/9 (0.00%)  1/11 (9.09%)  1/10 (10.00%)  8/70 (11.43%)  8/67 (11.94%) 
Injury, poisoning and procedural complications             
Contusion * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  1/10 (10.00%)  1/70 (1.43%)  1/67 (1.49%) 
Excoriation * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  3/70 (4.29%)  0/67 (0.00%) 
Fall * 1  0/11 (0.00%)  0/9 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  2/70 (2.86%)  4/67 (5.97%) 
Joint dislocation * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Laceration * 1  0/11 (0.00%)  0/9 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Limb injury * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Lip injury * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Radius fracture * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Investigations             
Alanine aminotransferase abnormal * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Alanine aminotransferase increased * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  1/70 (1.43%)  3/67 (4.48%) 
Aspartate aminotransferase abnormal * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Aspartate aminotransferase increased * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  4/67 (5.97%) 
Blood bilirubin abnormal * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Blood potassium decreased * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  1/67 (1.49%) 
Blood pressure increased * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/70 (1.43%)  2/67 (2.99%) 
Hepatic enzyme increased * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  2/10 (20.00%)  0/70 (0.00%)  0/67 (0.00%) 
Red blood cells urine positive * 1  0/11 (0.00%)  1/9 (11.11%)  1/11 (9.09%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
Transaminases increased * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
White blood cells urine positive * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Fluid imbalance * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  2/67 (2.99%) 
Hypokalaemia * 1  0/11 (0.00%)  1/9 (11.11%)  1/11 (9.09%)  1/10 (10.00%)  7/70 (10.00%)  3/67 (4.48%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  3/70 (4.29%)  3/67 (4.48%) 
Back pain * 1  1/11 (9.09%)  0/9 (0.00%)  2/11 (18.18%)  0/10 (0.00%)  1/70 (1.43%)  1/67 (1.49%) 
Gouty arthritis * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
Muscular weakness * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Musculoskeletal pain * 1  1/11 (9.09%)  1/9 (11.11%)  2/11 (18.18%)  0/10 (0.00%)  3/70 (4.29%)  1/67 (1.49%) 
Pain in extremity * 1  0/11 (0.00%)  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%)  9/70 (12.86%)  4/67 (5.97%) 
Nervous system disorders             
Dementia * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Dizziness * 1  2/11 (18.18%)  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  3/67 (4.48%) 
Haemorrhagic transformation stroke * 1  2/11 (18.18%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  1/67 (1.49%) 
Headache * 1  4/11 (36.36%)  3/9 (33.33%)  1/11 (9.09%)  0/10 (0.00%)  5/70 (7.14%)  7/67 (10.45%) 
Somnolence * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  2/70 (2.86%)  2/67 (2.99%) 
Syncope * 1  1/11 (9.09%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Psychiatric disorders             
Depressed mood * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  5/70 (7.14%)  3/67 (4.48%) 
Depression * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  4/70 (5.71%)  4/67 (5.97%) 
Insomnia * 1  0/11 (0.00%)  2/9 (22.22%)  0/11 (0.00%)  0/10 (0.00%)  7/70 (10.00%)  2/67 (2.99%) 
Sleep disorder * 1  3/11 (27.27%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  4/70 (5.71%)  1/67 (1.49%) 
Renal and urinary disorders             
Albuminuria * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Dysuria * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  5/70 (7.14%)  4/67 (5.97%) 
Haematuria * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  7/70 (10.00%)  2/67 (2.99%) 
Renal cyst * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Renal failure acute * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/70 (1.43%)  2/67 (2.99%) 
Urethral haemorrhage * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
Urinary retention * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  3/70 (4.29%)  1/67 (1.49%) 
Respiratory, thoracic and mediastinal disorders             
Atelectasis * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  2/70 (2.86%)  0/67 (0.00%) 
Bronchiectasis * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Cough * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  4/70 (5.71%)  2/67 (2.99%) 
Dyspnoea * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  3/67 (4.48%) 
Pleural effusion * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  1/10 (10.00%)  1/70 (1.43%)  0/67 (0.00%) 
Pulmonary congestion * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
Pulmonary embolism * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  1/70 (1.43%)  0/67 (0.00%) 
Sleep apnoea syndrome * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Skin and subcutaneous tissue disorders             
Dermatitis contact * 1  2/11 (18.18%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Dermatitis diaper * 1  1/11 (9.09%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/70 (0.00%)  0/67 (0.00%) 
Erythema * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  5/70 (7.14%)  0/67 (0.00%) 
Pruritus * 1  0/11 (0.00%)  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Vascular disorders             
Aortic aneurysm * 1  0/11 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%)  0/70 (0.00%)  0/67 (0.00%) 
Deep vein thrombosis * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  1/70 (1.43%)  1/67 (1.49%) 
Haematoma * 1  0/11 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%)  1/70 (1.43%)  0/67 (0.00%) 
Hypertension * 1  1/11 (9.09%)  4/9 (44.44%)  0/11 (0.00%)  1/10 (10.00%)  3/70 (4.29%)  2/67 (2.99%) 
Hypotension * 1  1/11 (9.09%)  1/9 (11.11%)  0/11 (0.00%)  1/10 (10.00%)  4/70 (5.71%)  7/67 (10.45%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
The study was terminated prematurely due to demonstrated futility at interim analysis. The final results are consistent with interim results.
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
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01208233     History of Changes
Other Study ID Numbers: A9541004
2010-021414-32 ( EudraCT Number )
First Submitted: September 22, 2010
First Posted: September 23, 2010
Results First Submitted: February 19, 2015
Results First Posted: February 19, 2016
Last Update Posted: February 19, 2016