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

Sponsor

Pfizer (Industry)

Overall Status

Terminated

CT.gov ID

NCT01208233

Collaborator

(none)

181

Enrollment

Locations

Arms

Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of PF-03049423 following multiple dose administration to subjects with ischemic stroke. The study will also evaluate the efficacy of PF-03049423, relative to placebo, in subjects with ischemic stroke following 90 days of therapy. The study will also explore the relationship between PF-03049423 concentration and blood pressure.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: PF-03049423 Drug: PF-03049423 Drug: PF-03049423 Other: Placebo	Phase 2

Detailed Description

The interim analysis for the POC study A9541004 demonstrated futility, and the study was stopped on the 6th of November 2013. There were no signals of serious safety concern.

Study Design

Study Type:

Interventional

Actual Enrollment :

181 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Multicenter, Randomized, Double Blind, Placebo Controlled Study Of The Safety And Efficacy Of Pf-03049423 In Subjects With Ischemic Stroke

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 mg PF-03049423	Drug: PF-03049423 1 mg of PF-03049423 daily for 90 days
Experimental: 3 mg of PF-03049423	Drug: PF-03049423 3 mg of PF-03049423 daily for 90 days
Experimental: 6 mg of PF-03049423	Drug: PF-03049423 6 mg of PF-03049423 daily for 90 days
Placebo Comparator: Placebo	Other: Placebo Placebo of PF-03049423 daily for 90 days

Outcome Measures

Primary Outcome Measures

Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2) [Day 1 (Baseline) up to Day 90]
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.
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern (Part 1* and 2) [Day 1 (Baseline) up to follow-up (28 days after Day 90)]
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.
Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern (Part 1* and 2) [Day 1 (Baseline) to Day 90]
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.
Number of Participants With Significant Change in Physical Examination Findings (Part 1* and 2) [Day 1 (Baseline) up to Day 90]
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.
Number of Participants With Significant Change in Neurological Examination Findings (Part 1* and 2) [Day 1 (Baseline) up to Day 90]
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.
Number of Participants With Suicidal Behavior and/or Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Part 1* and 2) [Day 7 (Baseline) up to follow up (28 days after Day 90)]
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.
Percentage of Participants With Modified Rankin Scale (mRS) Less Than or Equal to (<=2) at Day 90 (Part 2) [Day 90]
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).

Secondary Outcome Measures

Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic Hand (Part 2) [Day 1 (Baseline), Day 90]
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.
Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2) [Day 1 (Baseline), Day 90]
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.
Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic and Non-paretic Hands (Part 2) [Day 1 (Baseline), Day 90]
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.
Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2) [Day 1 (Baseline), Day 90]
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.
Percentage of Participants With mRS (0-1) at Day 90 (Part 2) [Day 90]
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).
Percentage of Participants With National Institutes of Health Stroke Scale (NIHSS) (0-1) at Day 90 (Part 2) [Day 90]
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.
Change From Baseline in NIHSS at Day 90 (Part 2) [Day 1 (Baseline), Day 90]
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.
Percentage of Participants With Barthel Index (BI) >= 95 and BI =100 at Day 90 (Part 2) [Day 90]
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.
BI at Day 90 (Part 2) [Day 90]
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.
Domains of Interest: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding Sub Test at Day 90 (Part 2) [Day 1 (Baseline), Day 90]
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.
Domains of Interest: Change From Baseline in RBANS Naming Sub Test at Day 90 (Part 2) [Day 1 (Baseline), Day 90]
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.
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) [Day 1 (Baseline), Day 90]
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.
Domains of Interest: Change From Baseline in Line Cancellation Test at Day 90 [(L-R)/(L+R)] (Part 2) [Day 1 (Baseline), Day 90]
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.
Domains of Interest: Change From Baseline in Recognition Memory Test at Day 90 (Part 2) [Day 1 (Baseline), Day 90]
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.
Gait Velocity Test at Day 90 (Part 2) [Day 90]
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.
Plasma Concentrations of PF-03049423 (Part 1 and 2) [Days 1, 2, 7, 14, 30, 60 and 90]
Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Non-paretic Hand (Part 2) [Day 1 (Baseline), Day 90]
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.

Other Outcome Measures

All-cause Mortality (Part 2) [The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.]
Deaths regardless causality were reported.
Mortality Directly Related to Stroke (Part 2) [The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.]
Deaths caused by stroke were reported.
Number of Participants With Neuro-worsening (Part 2) [Day 1 (Baseline) up to Day 90]
NIHSS change of 4 points or greater.
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) [Day 1 (Baseline) up to Day 14]
Treatment-emergent Adverse Events (AEs) Resulting in Discontinuation of Study Drug (Part 2) [Day 1 (Baseline) up to follow-up (28 days after Day 90)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of ischemic stroke with an onset within 72 hours prior to start of study agent administration, male or female.
Supratentorial ischemic stroke involving the cortex documented by neurological exam and confirmed by MRI.
Stroke involving upper extremity.
Subjects who received thrombolytic therapy may be enrolled and the use of antiplatelet is acceptable.

Exclusion Criteria:

Any other severe acute or chronic medical or psychiatric condition besides the stroke.
Women of child bearing potential.
Uncontrolled hypertension.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spain Rehabilitation Center	Birmingham	Alabama	United States	35233
2	The Kirklin Clinic	Birmingham	Alabama	United States	35233
3	University Hospital	Birmingham	Alabama	United States	35294-3280
4	Broward Health North	Deerfield Beach	Florida	United States	33064
5	Neurologic Consultant, P.A.	Fort Lauderdale	Florida	United States	33308
6	Fawcett Memorial Hospital	Port Charlotte	Florida	United States	33952
7	Neurostudies, Inc.	Port Charlotte	Florida	United States	33952
8	Jagdish Sidhpura M.D.	Columbus	Georgia	United States	31901
9	Jose Canedo, M.D., West Georgia Neurology	Columbus	Georgia	United States	31904
10	St. Francis Hospital	Columbus	Georgia	United States	31904
11	Muscogee Manor & Rehabilitation Center	Columbus	Georgia	United States	31907
12	Medical Research & Health Education Foundation, Inc.	Columbus	Georgia	United States	31909
13	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
14	Fort Wayne Neurological Center	Fort Wayne	Indiana	United States	46845
15	Parkview Regional Medical Center	Fort Wayne	Indiana	United States	46845
16	Parkview Research Center	Fort Wayne	Indiana	United States	46845
17	Norwood Nursing Center	Huntington	Indiana	United States	46750
18	Massachusetts General Hospital/Department of Neurology	Boston	Massachusetts	United States	02114
19	Spaulding Rehabilitation Hospital	Boston	Massachusetts	United States	02129
20	Wayne State University	Detroit	Michigan	United States	48201
21	Barnes-Jewish Hospital	St. Louis	Missouri	United States	63110
22	Rehabilitation Institute of St. Louis	St. Louis	Missouri	United States	63110
23	UNC HealthCare	Chapel Hill	North Carolina	United States	27514
24	UNC Department of Neurology Stroke Division	Chapel Hill	North Carolina	United States	27599-7025
25	Investigational Drug Services at OU Medical Center	Oklahoma City	Oklahoma	United States	73104
26	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
27	OU Medical Center	Oklahoma City	Oklahoma	United States	73104
28	OU Physicians Building	Oklahoma City	Oklahoma	United States	73104
29	Penn State Milton South Hershey Medical Center / Penn State College of Medicine	Hershey	Pennsylvania	United States	17033
30	Penn State Hershey Rehabilitation Hospital	Hummelstown	Pennsylvania	United States	17036
31	The Methodist Hospital Neurological Institute	Houston	Texas	United States	77030
32	The Methodist Hospital	Houston	Texas	United States	77030
33	Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti	Pleven		Bulgaria	5800
34	MBAL Kaspela	Plovdiv		Bulgaria	4002
35	MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti	Sofia		Bulgaria	1113
36	Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia	Sofia		Bulgaria	1202
37	MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya	Sofia		Bulgaria	1407
38	Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia	Sofia		Bulgaria	1431
39	UMBAL Tsaritsa Yoanna, Klinika po nevrologia	Sofia		Bulgaria	1527
40	Grey Nuns Community Hospital	Edmonton	Alberta	Canada	T6L 5X8
41	Fakultni nemocnice u sv. Anny v Brne	Brno		Czech Republic	65691
42	Fakultni nemocnice Plzen	Plzen - Lochotin		Czech Republic	304 60
43	CHU Pellegrin	Bordeaux		France	33076
44	CHU La Pitie Salpetriere	Paris Cedex 13		France	75651
45	Klinikum Altenburger Land	Altenburg		Germany	04600
46	Universitaetsklinikum Essen, Neurologische Klinik	Essen		Germany	45122
47	Universitaetsklinikum Leipzig	Leipzig		Germany	04103
48	Klinikum Rechts der Isar, Neurologische Klinik	Muenchen		Germany	81675
49	Universitaetsklinikum Muenster	Muenster		Germany	48149
50	Universitaet Regensburg	Regensburg		Germany	93053
51	Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly	Balassagyarmat		Hungary	2660
52	Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia	Budapest		Hungary	1076
53	Semmelweis Egyetem AOK / Neurologiai Klinika	Budapest		Hungary	1083
54	Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly	Budapest		Hungary	1134
55	Orszagos Idegtudomanyi Intezet, Stroke-ambulancia	Budapest		Hungary	1145
56	Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly	Gyor		Hungary	9024
57	KEM Hospital	Pune	Maharashtra	India	411011
58	Max Super Speciality Hospital	New Delhi		India	110017
59	Seoul National University Bundang Hospital, Department of Neurology	Seongnam-si	Gyeonggi-do	Korea, Republic of	463-707
60	Hallym University Sacred Heart Hospital, Department of Neurology	Anyang-si	Gyonggi-do	Korea, Republic of	431-070
61	Chonnam National University Hospital, Department of Neurology	Gwangju		Korea, Republic of	501-757
62	Inha University Hospital, Department of Neurology	Incheon		Korea, Republic of	400-711
63	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
64	Severance Hospital, Yonsei University College of Medicine, Department of Neurology	Seoul		Korea, Republic of	120-752
65	Samsung Medical Center, Department of Neurology	Seoul		Korea, Republic of	135710
66	Asan Medical Center, Department of Neurology	Seoul		Korea, Republic of	138-736
67	Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	833
68	China Medical University Hospital	Taichung		Taiwan	404
69	National Taiwan University Hospital	Taipei		Taiwan	100
70	Chang Gung Medical Foundation-Linkou Branch	Taoyuan County		Taiwan	333

Sponsors and Collaborators

Pfizer

Investigators

Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

To obtain contact information for a study center near you, click here.

Publications

None provided.

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01208233

Other Study ID Numbers:

A9541004
2010-021414-32

First Posted:

Sep 23, 2010

Last Update Posted:

Feb 19, 2016

Last Verified:

Jan 1, 2016

Keywords provided by Pfizer

Phase 2 Ischemic stroke Safety and efficacy

Additional relevant MeSH terms:

3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido(3,4-b)pyrazin-2(1H)-one

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	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
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

Baseline Characteristics

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
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 Participants	11	9	11	10	70	67	178
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	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 (Count of Participants)
Female	4 36.4%	2 22.2%	7 63.6%	3 30%	28 40%	26 38.8%	70 39.3%
Male	7 63.6%	7 77.8%	4 36.4%	7 70%	42 60%	41 61.2%	108 60.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2)
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

Outcome Measure Data

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
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.
Measure Participants	11	9	10	10	70	66
Number [participants]	8 72.7%	8 88.9%	10 90.9%	9 90%	64 91.4%	56 83.6%

2. Primary Outcome

Title	Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern (Part 1* and 2)
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)

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
Supine SBP <90 mm Hg, n=11,9,11,10,70,67	0 0%	1 11.1%	1 9.1%	0 0%	3 4.3%	0 0%
Sitting SBP <90 mm Hg, n=10,8,9,5,55,59	0 0%	1 11.1%	1 9.1%	0 0%	2 2.9%	2 3%
Standing SBP <90 mm Hg, n=7,7,9,8,49,48	0 0%	0 0%	0 0%	0 0%	1 1.4%	1 1.5%
Supine DBP <50 mm Hg, n=11,9,11,10,70,67	0 0%	0 0%	2 18.2%	1 10%	6 8.6%	4 6%
Sitting DBP <50 mm Hg, n=10,8,9,5,55,59	0 0%	0 0%	0 0%	0 0%	3 4.3%	1 1.5%
Standing DBP <50 mm Hg, n=7,7,9,8,49,48	0 0%	0 0%	0 0%	1 10%	2 2.9%	3 4.5%
Supine pulse rate <40 bpm, n=11,9,11,10,70,67	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%
Supine pulse rate >120 bpm, n=11,9,11,10,70,67	0 0%	0 0%	1 9.1%	0 0%	5 7.1%	7 10.4%
Increase:supine SBP >=30 mm Hg, n=11,9,11,10,70,67	2 18.2%	3 33.3%	5 45.5%	3 30%	13 18.6%	17 25.4%
Increase: sitting SBP >=30 mm Hg, n=9,6,9,4,48,44	0 0%	2 22.2%	2 18.2%	0 0%	10 14.3%	9 13.4%
Increase: standing SBP >=30 mm Hg, n=2,3,3,6,19,22	0 0%	0 0%	0 0%	2 20%	2 2.9%	1 1.5%
Increase:supine DBP >=20 mm Hg, n=11,9,11,10,70,67	4 36.4%	2 22.2%	5 45.5%	2 20%	16 22.9%	22 32.8%
Increase: sitting DBP >=20 mm Hg, n=9,6,9,4,48,44	3 27.3%	1 11.1%	2 18.2%	2 20%	9 12.9%	12 17.9%
Increase: standing DBP >=20 mm Hg, n=2,3,3,6,19,22	0 0%	0 0%	0 0%	2 20%	3 4.3%	3 4.5%
Decrease:supine SBP >=30 mm Hg, n=11,9,11,10,70,67	7 63.6%	6 66.7%	5 45.5%	4 40%	37 52.9%	37 55.2%
Decrease: sitting SBP >=30 mm Hg, n=9,6,9,4,48,44	3 27.3%	4 44.4%	6 54.5%	2 20%	26 37.1%	18 26.9%
Decrease: standing SBP >=30 mm Hg, n=2,3,3,6,19,22	2 18.2%	2 22.2%	0 0%	2 20%	10 14.3%	11 16.4%
Decrease:supine DBP >=20 mm Hg, n=11,9,11,10,70,67	8 72.7%	6 66.7%	6 54.5%	3 30%	32 45.7%	26 38.8%
Decrease: sitting DBP >=20 mm Hg, n=9,6,9,4,48,44	1 9.1%	4 44.4%	5 45.5%	1 10%	23 32.9%	14 20.9%
Decrease: standing DBP >=20 mm Hg, n=2,3,3,6,19,22	2 18.2%	2 22.2%	1 9.1%	2 20%	6 8.6%	11 16.4%
Decrease:supine SBP >=50 mm Hg, n=11,9,11,10,70,67	2 18.2%	0 0%	1 9.1%	2 20%	10 14.3%	9 13.4%
Decrease: sitting SBP >=50 mm Hg, n=9,6,9,4,48,44	2 18.2%	1 11.1%	3 27.3%	0 0%	7 10%	6 9%
Decrease: standing SBP >=50 mm Hg, n=2,3,3,6,19,22	1 9.1%	0 0%	0 0%	0 0%	1 1.4%	2 3%
Sitting pulse rate <40 bpm, n=1,0,2,0,3,2	0 0%	NA NaN	0 0%	NA NaN	0 0%	0 0%
Standing pulse rate <40 bpm, n=0,0,0,2,1,0	NA NaN	NA NaN	NA NaN	0 0%	0 0%	NA NaN
Sitting pulse rate >120 bpm, n=1,0,2,0,3,2	0 0%	NA NaN	0 0%	NA NaN	0 0%	0 0%
Standing pulse rate >140 bpm, n=0,0,0,2,1,0	NA NaN	NA NaN	NA NaN	0 0%	0 0%	NA NaN

3. Primary Outcome

Title	Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern (Part 1* and 2)
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

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
PR interval >=300 msec, n=11,9,11,10,70,67	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
QRS interval >=140 msec, n=11,9,11,10,70,67	1 9.1%	0 0%	1 9.1%	1 10%	0 0%	1 1.5%
QT interval >=500 msec, n=11,9,11,10,70,67	0 0%	0 0%	0 0%	0 0%	4 5.7%	1 1.5%
QTcF interval 450-480 msec, n=11,9,11,10,70,67	2 18.2%	3 33.3%	4 36.4%	2 20%	14 20%	14 20.9%
QTcF interval 480-500 msec, n=11,9,11,10,70,67	0 0%	1 11.1%	0 0%	1 10%	4 5.7%	3 4.5%
QTcF interval >=500 msec, n=11,9,11,10,70,67	0 0%	0 0%	1 9.1%	0 0%	0 0%	1 1.5%
PR interval increase >=25%/50%, n=10,7,9,9,52,47	0 0%	0 0%	1 9.1%	0 0%	1 1.4%	0 0%
QRS interval increase >=50%, n=10,9,11,10,69,66	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.5%
QTcF increase 30-60 msec, n=10,9,11,10,69,66	2 18.2%	3 33.3%	4 36.4%	2 20%	19 27.1%	11 16.4%
QTcF increase >=60 msec, n=10,9,11,10,69,66	0 0%	0 0%	0 0%	1 10%	3 4.3%	5 7.5%

4. Primary Outcome

Title	Number of Participants With Significant Change in Physical Examination Findings (Part 1* and 2)
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

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	66
Number [participants]	1 9.1%	1 11.1%	0 0%	0 0%	2 2.9%	0 0%

5. Primary Outcome

Title	Number of Participants With Significant Change in Neurological Examination Findings (Part 1* and 2)
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

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	66
Number [participants]	1 9.1%	1 11.1%	0 0%	0 0%	4 5.7%	0 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)
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)

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
Day 7, n=0, 0, 1, 1, 64, 57	NA NaN	NA NaN	0 0%	0 0%	1 1.4%	2 3%
Day 14, n=0, 0, 1, 1, 59, 53	NA NaN	NA NaN	0 0%	0 0%	1 1.4%	0 0%
Day 30, n=0, 0, 1, 1, 60, 47	NA NaN	NA NaN	0 0%	0 0%	2 2.9%	0 0%
Day 60, n=0, 0, 1, 1, 55, 44	NA NaN	NA NaN	0 0%	0 0%	2 2.9%	0 0%
Day 90, n=0, 0, 1, 1, 61, 53	NA NaN	NA NaN	0 0%	0 0%	1 1.4%	1 1.5%
Follow-up, n=0, 0, 1, 1, 59, 51	NA NaN	NA NaN	0 0%	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Percentage of Participants With Modified Rankin Scale (mRS) Less Than or Equal to (<=2) at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	68	65
Last Observation Carried Forward (LOCF), n=68, 65	42.6 387.3%	46.2 513.3%
Observed Cases (OC), n=51, 52	47.1 428.2%	50.0 555.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4962
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2517
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic Hand (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	21	24
Least Squares Mean (Standard Error) [blocks moved per minute]	26.881 (3.8667)	26.741 (3.5627)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	Paretic hand
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9716
	Comments
	Method	Mixed Models Analysis
	Comments

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

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)
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

Outcome Measure Data

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
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.
Measure Participants	21	24
Least Squares Mean (Standard Error) [percentage change]	41.830 (7.7810)	31.041 (7.1284)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	Paretic to non-paretic hand ratio (%)
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1417
	Comments
	Method	Mixed Models Analysis
	Comments

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

10. Secondary Outcome

Title	Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic and Non-paretic Hands (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	68	65
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	Paretic hand
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0611
	Comments
	Method	Mixed Models Analysis
	Comments

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

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	Non-paretic hand
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9433
	Comments
	Method	Mixed Models Analysis
	Comments

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

11. Secondary Outcome

Title	Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	26	26
Least Squares Mean (Standard Error) [percentage change]	23.949 (5.4499)	36.761 (5.1182)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	Paretic to non-paretic hand ratio (%)
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0654
	Comments
	Method	Mixed Models Analysis
	Comments

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

12. Secondary Outcome

Title	Percentage of Participants With mRS (0-1) at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	68	65
Number [percentage of participants]	25.0 227.3%	24.6 273.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	LOCF was used to impute missing data.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9510
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.972
	Confidence Interval	(2-Sided) 80% 0.54 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With National Institutes of Health Stroke Scale (NIHSS) (0-1) at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	68	65
Number [percentage of participants]	25.0 227.3%	26.2 291.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	LOCF was used to impute missing data.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7234
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.854
	Confidence Interval	(2-Sided) 80% 0.48 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in NIHSS at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	49	47
Least Squares Mean (Standard Error) [unit on a scale]	-6.511 (0.5384)	-6.228 (0.5655)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6759
	Comments
	Method	Mixed Models Analysis
	Comments

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

15. Secondary Outcome

Title	Percentage of Participants With Barthel Index (BI) >= 95 and BI =100 at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	68	65
BI >=95	47.1 428.2%	40.0 444.4%
BI=100	42.6 387.3%	35.4 393.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	BI >=95, LOCF was used to impute missing data.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4213
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.433
	Confidence Interval	(2-Sided) 80% 0.81 to 2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	BI=100, LOCF was used to impute missing data.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2760
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.651
	Confidence Interval	(2-Sided) 80% 0.92 to 2.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	BI at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	49	47
Least Squares Mean (Standard Error) [unit on a scale]	79.151 (3.6248)	73.552 (3.8471)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2118
	Comments
	Method	Mixed Models Analysis
	Comments

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

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)
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

Outcome Measure Data

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
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.
Measure Participants	33	28
Least Squares Mean (Standard Error) [correct responses]	13.748 (1.5321)	12.686 (1.6282)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5541
	Comments
	Method	Mixed Models Analysis
	Comments

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

18. Secondary Outcome

Title	Domains of Interest: Change From Baseline in RBANS Naming Sub Test at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	41	37
Least Squares Mean (Standard Error) [objects named correctly]	0.989 (0.3676)	1.324 (0.3666)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4260
	Comments
	Method	Mixed Models Analysis
	Comments

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

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)
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

Outcome Measure Data

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
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.
Measure Participants	68	65
(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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	(L+R)/28 × 100%
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6500
	Comments
	Method	Mixed Models Analysis
	Comments

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

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	(L/14) × 100%
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5671
	Comments
	Method	Mixed Models Analysis
	Comments

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

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	(R/14) × 100%
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8430
	Comments
	Method	Mixed Models Analysis
	Comments

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

20. Secondary Outcome

Title	Domains of Interest: Change From Baseline in Line Cancellation Test at Day 90 [(L-R)/(L+R)] (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	39	34
Least Squares Mean (Standard Error) [change in ratio]	0.083 (0.0620)	-0.023 (0.0625)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	(L R)/(L+R)
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1512
	Comments
	Method	Mixed Models Analysis
	Comments

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

21. Secondary Outcome

Title	Domains of Interest: Change From Baseline in Recognition Memory Test at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	44	37
Least Squares Mean (Standard Error) [pictures correctly identified]	-1.135 (0.4743)	0.144 (0.4797)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0128
	Comments
	Method	Mixed Models Analysis
	Comments

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

22. Secondary Outcome

Title	Gait Velocity Test at Day 90 (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	41	36
Least Squares Mean (Standard Error) [meters/second (m/s)]	1.064 (0.1040)	0.975 (0.1128)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4713
	Comments
	Method	Mixed Models Analysis
	Comments

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

23. Secondary Outcome

Title	Plasma Concentrations of PF-03049423 (Part 1 and 2)
Description
Time Frame	Days 1, 2, 7, 14, 30, 60 and 90

Outcome Measure Data

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
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.
Measure Participants	11	11	70
Day 1 (0 hour predose), n=0, 1, 3	NA (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 (NA)	51.80 (NA)	115.9 (65.329)
Day 7 (2 hours post dose), n=0, 1, 59	NA (NA)	58.10 (NA)	126.3 (57.759)
Day 7 (6 hours post dose), n=0, 1, 61	NA (NA)	51.10 (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 (NA)
Day 14 (2 hours post dose), n=9, 6, 0	17.06 (7.3799)	70.37 (14.795)	NA (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)

24. Other Pre-specified Outcome

Title	All-cause Mortality (Part 2)
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.

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
Number [Number of participants]	0 0%	0 0%	0 0%	0 0%	6 8.6%	7 10.4%

25. Other Pre-specified Outcome

Title	Mortality Directly Related to Stroke (Part 2)
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.

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
Number [Number of participants]	0 0%	0 0%	0 0%	0 0%	3 4.3%	0 0%

26. Other Pre-specified Outcome

Title	Number of Participants With Neuro-worsening (Part 2)
Description	NIHSS change of 4 points or greater.
Time Frame	Day 1 (Baseline) up to Day 90

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
Number [Number of participants]	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN

27. 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)
Description
Time Frame	Day 1 (Baseline) up to Day 14

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
Number [Number of participants]	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN

28. Other Pre-specified Outcome

Title	Treatment-emergent Adverse Events (AEs) Resulting in Discontinuation of Study Drug (Part 2)
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)

Outcome Measure Data

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
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.
Measure Participants	11	9	11	10	70	67
Number [Number of participants]	0 0%	1 11.1%	2 18.2%	0 0%	3 4.3%	5 7.5%

29. Secondary Outcome

Title	Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Non-paretic Hand (Part 2)
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

Outcome Measure Data

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
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.
Measure Participants	45	41
Least Squares Mean (Standard Error) [blocks moved per minute]	17.797 (2.1676)	18.313 (2.2407)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: PF-03049423 1 mg, Cohort 1: Placebo
	Comments	Non-paretic hand
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8501
	Comments
	Method	Mixed Models Analysis
	Comments

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

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
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
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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)		1/9 (11.1%)		3/11 (27.3%)		1/10 (10%)		15/70 (21.4%)		18/67 (26.9%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Cardiac disorders
Acute myocardial infarction	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		2/67 (3%)
Angina pectoris	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Atrial fibrillation	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		1/67 (1.5%)
Cardiac arrest	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Cardiac failure	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Cardiac failure congestive	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Myocardial infarction	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		1/67 (1.5%)
Haematochezia	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Ileus paralytic	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
Intestinal obstruction	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
General disorders
Condition aggravated	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Death	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Hepatobiliary disorders
Cholangitis	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Infections and infestations
Pneumonia	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Sepsis	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		1/67 (1.5%)
Urinary tract infection	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		2/67 (3%)
Urosepsis	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Injury, poisoning and procedural complications
Concussion	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Fall	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Femur fracture	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Radius fracture	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Investigations
Electrocardiogram ST-T change	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Hepatic enzyme increased	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Nervous system disorders
Brain oedema	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Cerebral haemorrhage	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Cerebral infarction	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Cerebrovascular accident	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		1/67 (1.5%)
Epilepsy	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		2/67 (3%)
Haemorrhage intracranial	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Ischaemic cerebral infarction	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Ischaemic stroke	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		1/70 (1.4%)		0/67 (0%)
Subarachnoid haemorrhage	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Psychiatric disorders
Disorientation	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Renal and urinary disorders
Haematuria	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Respiratory, thoracic and mediastinal disorders
Asphyxia	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Pneumonia aspiration	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		2/67 (3%)
Pulmonary embolism	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		3/70 (4.3%)		0/67 (0%)
Other (Not Including 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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)		7/9 (77.8%)		7/11 (63.6%)		9/10 (90%)		50/70 (71.4%)		47/67 (70.1%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		4/70 (5.7%)		3/67 (4.5%)
Leukocytosis	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Neutrophilia	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Thrombocytopenia	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Cardiac disorders
Atrial fibrillation	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		2/70 (2.9%)		1/67 (1.5%)
Bradycardia	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		2/70 (2.9%)		1/67 (1.5%)
Coronary artery occlusion	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Supraventricular extrasystoles	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Congenital, familial and genetic disorders
Atrial septal defect	0/11 (0%)		2/9 (22.2%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		2/67 (3%)
Ear and labyrinth disorders
Vertigo	1/11 (9.1%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		2/70 (2.9%)		0/67 (0%)
Eye disorders
Conjunctival hyperaemia	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		1/70 (1.4%)		0/67 (0%)
Eye disorder	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
Gastrointestinal disorders
Abdominal distension	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Abdominal pain upper	1/11 (9.1%)		1/9 (11.1%)		0/11 (0%)		1/10 (10%)		2/70 (2.9%)		1/67 (1.5%)
Constipation	0/11 (0%)		1/9 (11.1%)		1/11 (9.1%)		1/10 (10%)		8/70 (11.4%)		14/67 (20.9%)
Diarrhoea	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		9/70 (12.9%)		10/67 (14.9%)
Dyspepsia	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		1/10 (10%)		1/70 (1.4%)		3/67 (4.5%)
Gastritis	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Nausea	1/11 (9.1%)		2/9 (22.2%)		1/11 (9.1%)		0/10 (0%)		2/70 (2.9%)		4/67 (6%)
Vomiting	0/11 (0%)		0/9 (0%)		2/11 (18.2%)		0/10 (0%)		1/70 (1.4%)		4/67 (6%)
General disorders
Face oedema	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Feeling cold	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Oedema peripheral	0/11 (0%)		0/9 (0%)		2/11 (18.2%)		0/10 (0%)		3/70 (4.3%)		3/67 (4.5%)
Pyrexia	1/11 (9.1%)		0/9 (0%)		2/11 (18.2%)		0/10 (0%)		7/70 (10%)		6/67 (9%)
Infections and infestations
Genitourinary tract infection	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Herpes zoster	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Upper respiratory tract infection	1/11 (9.1%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		3/70 (4.3%)		2/67 (3%)
Urinary tract infection	1/11 (9.1%)		0/9 (0%)		1/11 (9.1%)		1/10 (10%)		8/70 (11.4%)		8/67 (11.9%)
Injury, poisoning and procedural complications
Contusion	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		1/10 (10%)		1/70 (1.4%)		1/67 (1.5%)
Excoriation	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		3/70 (4.3%)		0/67 (0%)
Fall	0/11 (0%)		0/9 (0%)		2/11 (18.2%)		0/10 (0%)		2/70 (2.9%)		4/67 (6%)
Joint dislocation	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Laceration	0/11 (0%)		0/9 (0%)		2/11 (18.2%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Limb injury	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Lip injury	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Radius fracture	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Investigations
Alanine aminotransferase abnormal	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Alanine aminotransferase increased	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		1/70 (1.4%)		3/67 (4.5%)
Aspartate aminotransferase abnormal	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Aspartate aminotransferase increased	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		4/67 (6%)
Blood bilirubin abnormal	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Blood potassium decreased	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		1/67 (1.5%)
Blood pressure increased	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		1/70 (1.4%)		2/67 (3%)
Hepatic enzyme increased	0/11 (0%)		0/9 (0%)		0/11 (0%)		2/10 (20%)		0/70 (0%)		0/67 (0%)
Red blood cells urine positive	0/11 (0%)		1/9 (11.1%)		1/11 (9.1%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
Transaminases increased	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
White blood cells urine positive	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Fluid imbalance	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		2/67 (3%)
Hypokalaemia	0/11 (0%)		1/9 (11.1%)		1/11 (9.1%)		1/10 (10%)		7/70 (10%)		3/67 (4.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		3/70 (4.3%)		3/67 (4.5%)
Back pain	1/11 (9.1%)		0/9 (0%)		2/11 (18.2%)		0/10 (0%)		1/70 (1.4%)		1/67 (1.5%)
Gouty arthritis	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
Muscular weakness	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Musculoskeletal pain	1/11 (9.1%)		1/9 (11.1%)		2/11 (18.2%)		0/10 (0%)		3/70 (4.3%)		1/67 (1.5%)
Pain in extremity	0/11 (0%)		1/9 (11.1%)		1/11 (9.1%)		0/10 (0%)		9/70 (12.9%)		4/67 (6%)
Nervous system disorders
Dementia	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Dizziness	2/11 (18.2%)		1/9 (11.1%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		3/67 (4.5%)
Haemorrhagic transformation stroke	2/11 (18.2%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		1/67 (1.5%)
Headache	4/11 (36.4%)		3/9 (33.3%)		1/11 (9.1%)		0/10 (0%)		5/70 (7.1%)		7/67 (10.4%)
Somnolence	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		2/70 (2.9%)		2/67 (3%)
Syncope	1/11 (9.1%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Psychiatric disorders
Depressed mood	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		5/70 (7.1%)		3/67 (4.5%)
Depression	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		4/70 (5.7%)		4/67 (6%)
Insomnia	0/11 (0%)		2/9 (22.2%)		0/11 (0%)		0/10 (0%)		7/70 (10%)		2/67 (3%)
Sleep disorder	3/11 (27.3%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		4/70 (5.7%)		1/67 (1.5%)
Renal and urinary disorders
Albuminuria	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Dysuria	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		5/70 (7.1%)		4/67 (6%)
Haematuria	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		7/70 (10%)		2/67 (3%)
Renal cyst	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Renal failure acute	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		1/70 (1.4%)		2/67 (3%)
Urethral haemorrhage	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
Urinary retention	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		3/70 (4.3%)		1/67 (1.5%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		2/70 (2.9%)		0/67 (0%)
Bronchiectasis	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Cough	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		4/70 (5.7%)		2/67 (3%)
Dyspnoea	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		3/67 (4.5%)
Pleural effusion	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		1/10 (10%)		1/70 (1.4%)		0/67 (0%)
Pulmonary congestion	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
Pulmonary embolism	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		1/70 (1.4%)		0/67 (0%)
Sleep apnoea syndrome	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	2/11 (18.2%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Dermatitis diaper	1/11 (9.1%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		0/70 (0%)		0/67 (0%)
Erythema	0/11 (0%)		0/9 (0%)		0/11 (0%)		0/10 (0%)		5/70 (7.1%)		0/67 (0%)
Pruritus	0/11 (0%)		1/9 (11.1%)		0/11 (0%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Vascular disorders
Aortic aneurysm	0/11 (0%)		0/9 (0%)		0/11 (0%)		1/10 (10%)		0/70 (0%)		0/67 (0%)
Deep vein thrombosis	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		1/70 (1.4%)		1/67 (1.5%)
Haematoma	0/11 (0%)		0/9 (0%)		1/11 (9.1%)		0/10 (0%)		1/70 (1.4%)		0/67 (0%)
Hypertension	1/11 (9.1%)		4/9 (44.4%)		0/11 (0%)		1/10 (10%)		3/70 (4.3%)		2/67 (3%)
Hypotension	1/11 (9.1%)		1/9 (11.1%)		0/11 (0%)		1/10 (10%)		4/70 (5.7%)		7/67 (10.4%)

Limitations/Caveats

The study was terminated prematurely due to demonstrated futility at interim analysis. The final results are consistent with interim results.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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
Email	ClinicalTrials.gov_Inquiries@pfizer.com

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01208233

Other Study ID Numbers:

A9541004
2010-021414-32

First Posted:

Sep 23, 2010

Last Update Posted:

Feb 19, 2016

Last Verified:

Jan 1, 2016

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

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Other Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

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Outcome Measure Data

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Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

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Outcome Measure Data

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Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

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Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

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Outcome Measure Data

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Outcome Measure Data

Outcome Measure Data

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Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality