search
Back to results

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

Primary Purpose

Ischemic Stroke

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-03049423
PF-03049423
PF-03049423
Placebo
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring Phase 2 Ischemic stroke Safety and efficacy

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Spain Rehabilitation Center
  • The Kirklin Clinic
  • University Hospital
  • Broward Health North
  • Neurologic Consultant, P.A.
  • Fawcett Memorial Hospital
  • Neurostudies, Inc.
  • Jagdish Sidhpura M.D.
  • Jose Canedo, M.D., West Georgia Neurology
  • St. Francis Hospital
  • Muscogee Manor & Rehabilitation Center
  • Medical Research & Health Education Foundation, Inc.
  • Parkview Hospital Randallia
  • Fort Wayne Neurological Center
  • Parkview Regional Medical Center
  • Parkview Research Center
  • Norwood Nursing Center
  • Massachusetts General Hospital/Department of Neurology
  • Spaulding Rehabilitation Hospital
  • Wayne State University
  • Barnes-Jewish Hospital
  • Rehabilitation Institute of St. Louis
  • UNC HealthCare
  • UNC Department of Neurology Stroke Division
  • Investigational Drug Services at OU Medical Center
  • Oklahoma University Health Sciences Center
  • OU Medical Center
  • OU Physicians Building
  • Penn State Milton South Hershey Medical Center / Penn State College of Medicine
  • Penn State Hershey Rehabilitation Hospital
  • The Methodist Hospital Neurological Institute
  • The Methodist Hospital
  • Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti
  • MBAL Kaspela
  • MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti
  • Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia
  • MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya
  • Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia
  • UMBAL Tsaritsa Yoanna, Klinika po nevrologia
  • Grey Nuns Community Hospital
  • Fakultni nemocnice u sv. Anny v Brne
  • Fakultni nemocnice Plzen
  • CHU Pellegrin
  • CHU La Pitie Salpetriere
  • Klinikum Altenburger Land
  • Universitaetsklinikum Essen, Neurologische Klinik
  • Universitaetsklinikum Leipzig
  • Klinikum Rechts der Isar, Neurologische Klinik
  • Universitaetsklinikum Muenster
  • Universitaet Regensburg
  • Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly
  • Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia
  • Semmelweis Egyetem AOK / Neurologiai Klinika
  • Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly
  • Orszagos Idegtudomanyi Intezet, Stroke-ambulancia
  • Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly
  • KEM Hospital
  • Max Super Speciality Hospital
  • Seoul National University Bundang Hospital, Department of Neurology
  • Hallym University Sacred Heart Hospital, Department of Neurology
  • Chonnam National University Hospital, Department of Neurology
  • Inha University Hospital, Department of Neurology
  • Seoul National University Hospital
  • Severance Hospital, Yonsei University College of Medicine, Department of Neurology
  • Samsung Medical Center, Department of Neurology
  • Asan Medical Center, Department of Neurology
  • Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital
  • China Medical University Hospital
  • National Taiwan University Hospital
  • Chang Gung Medical Foundation-Linkou Branch

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

1 mg PF-03049423

3 mg of PF-03049423

6 mg of PF-03049423

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Non-paretic Hand (Part 2)
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.

Full Information

First Posted
September 22, 2010
Last Updated
January 22, 2016
Sponsor
Pfizer
search

1. Study Identification

Unique Protocol Identification Number
NCT01208233
Brief Title
Study Evaluating The Safety And Efficacy Of PF-03049423 In Subjects With Ischemic Stroke
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 Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
December 2010 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
Phase 2 Ischemic stroke Safety and efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
181 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 mg PF-03049423
Arm Type
Experimental
Arm Title
3 mg of PF-03049423
Arm Type
Experimental
Arm Title
6 mg of PF-03049423
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
PF-03049423
Intervention Description
1 mg of PF-03049423 daily for 90 days
Intervention Type
Drug
Intervention Name(s)
PF-03049423
Intervention Description
3 mg of PF-03049423 daily for 90 days
Intervention Type
Drug
Intervention Name(s)
PF-03049423
Intervention Description
6 mg of PF-03049423 daily for 90 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo of PF-03049423 daily for 90 days
Primary Outcome Measure Information:
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
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)
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
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
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
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)
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Title
Plasma Concentrations of PF-03049423 (Part 1 and 2)
Time Frame
Days 1, 2, 7, 14, 30, 60 and 90
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
Other Pre-specified Outcome Measures:
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.
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.
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
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)
Time Frame
Day 1 (Baseline) up to Day 14
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Spain Rehabilitation Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
The Kirklin Clinic
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3280
Country
United States
Facility Name
Broward Health North
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33064
Country
United States
Facility Name
Neurologic Consultant, P.A.
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Fawcett Memorial Hospital
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
Facility Name
Neurostudies, Inc.
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
Facility Name
Jagdish Sidhpura M.D.
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31901
Country
United States
Facility Name
Jose Canedo, M.D., West Georgia Neurology
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
St. Francis Hospital
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
Muscogee Manor & Rehabilitation Center
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31907
Country
United States
Facility Name
Medical Research & Health Education Foundation, Inc.
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31909
Country
United States
Facility Name
Parkview Hospital Randallia
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46805
Country
United States
Facility Name
Fort Wayne Neurological Center
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
Facility Name
Parkview Regional Medical Center
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
Facility Name
Parkview Research Center
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
Facility Name
Norwood Nursing Center
City
Huntington
State/Province
Indiana
ZIP/Postal Code
46750
Country
United States
Facility Name
Massachusetts General Hospital/Department of Neurology
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Spaulding Rehabilitation Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Barnes-Jewish Hospital
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Rehabilitation Institute of St. Louis
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
UNC HealthCare
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
UNC Department of Neurology Stroke Division
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7025
Country
United States
Facility Name
Investigational Drug Services at OU Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Oklahoma University Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
OU Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
OU Physicians Building
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Penn State Milton South Hershey Medical Center / Penn State College of Medicine
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Penn State Hershey Rehabilitation Hospital
City
Hummelstown
State/Province
Pennsylvania
ZIP/Postal Code
17036
Country
United States
Facility Name
The Methodist Hospital Neurological Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
MBAL Kaspela
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti
City
Sofia
ZIP/Postal Code
1113
Country
Bulgaria
Facility Name
Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia
City
Sofia
ZIP/Postal Code
1202
Country
Bulgaria
Facility Name
MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya
City
Sofia
ZIP/Postal Code
1407
Country
Bulgaria
Facility Name
Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
UMBAL Tsaritsa Yoanna, Klinika po nevrologia
City
Sofia
ZIP/Postal Code
1527
Country
Bulgaria
Facility Name
Grey Nuns Community Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6L 5X8
Country
Canada
Facility Name
Fakultni nemocnice u sv. Anny v Brne
City
Brno
ZIP/Postal Code
65691
Country
Czech Republic
Facility Name
Fakultni nemocnice Plzen
City
Plzen - Lochotin
ZIP/Postal Code
304 60
Country
Czech Republic
Facility Name
CHU Pellegrin
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU La Pitie Salpetriere
City
Paris Cedex 13
ZIP/Postal Code
75651
Country
France
Facility Name
Klinikum Altenburger Land
City
Altenburg
ZIP/Postal Code
04600
Country
Germany
Facility Name
Universitaetsklinikum Essen, Neurologische Klinik
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitaetsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Klinikum Rechts der Isar, Neurologische Klinik
City
Muenchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
Universitaetsklinikum Muenster
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universitaet Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly
City
Balassagyarmat
ZIP/Postal Code
2660
Country
Hungary
Facility Name
Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia
City
Budapest
ZIP/Postal Code
1076
Country
Hungary
Facility Name
Semmelweis Egyetem AOK / Neurologiai Klinika
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly
City
Budapest
ZIP/Postal Code
1134
Country
Hungary
Facility Name
Orszagos Idegtudomanyi Intezet, Stroke-ambulancia
City
Budapest
ZIP/Postal Code
1145
Country
Hungary
Facility Name
Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly
City
Gyor
ZIP/Postal Code
9024
Country
Hungary
Facility Name
KEM Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411011
Country
India
Facility Name
Max Super Speciality Hospital
City
New Delhi
ZIP/Postal Code
110017
Country
India
Facility Name
Seoul National University Bundang Hospital, Department of Neurology
City
Seongnam-si
State/Province
Gyeonggi-do
ZIP/Postal Code
463-707
Country
Korea, Republic of
Facility Name
Hallym University Sacred Heart Hospital, Department of Neurology
City
Anyang-si
State/Province
Gyonggi-do
ZIP/Postal Code
431-070
Country
Korea, Republic of
Facility Name
Chonnam National University Hospital, Department of Neurology
City
Gwangju
ZIP/Postal Code
501-757
Country
Korea, Republic of
Facility Name
Inha University Hospital, Department of Neurology
City
Incheon
ZIP/Postal Code
400-711
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University College of Medicine, Department of Neurology
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Samsung Medical Center, Department of Neurology
City
Seoul
ZIP/Postal Code
135710
Country
Korea, Republic of
Facility Name
Asan Medical Center, Department of Neurology
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital
City
Kaohsiung
ZIP/Postal Code
833
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
404
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Chang Gung Medical Foundation-Linkou Branch
City
Taoyuan County
ZIP/Postal Code
333
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
26738812
Citation
Di Cesare F, Mancuso J, Woodward P, Bednar MM, Loudon PT; A9541004 Stroke Study Group. Phosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial. J Stroke Cerebrovasc Dis. 2016 Mar;25(3):642-9. doi: 10.1016/j.jstrokecerebrovasdis.2015.11.026. Epub 2015 Dec 28.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A9541004&StudyName=Study%20Evaluating%20The%20Safety%20And%20Efficacy%20Of%20PF-03049423%20In%20Subjects%20With%20Ischemic%20Stroke
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

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

We'll reach out to this number within 24 hrs