Study Evaluating The Safety And Efficacy Of PF-03049423 In Subjects With Ischemic Stroke
- Registration Number
- NCT01208233
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 181
- 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.
- Any other severe acute or chronic medical or psychiatric condition besides the stroke.
- Women of child bearing potential.
- Uncontrolled hypertension.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - 3 mg of PF-03049423 PF-03049423 - 6 mg of PF-03049423 PF-03049423 - 1 mg PF-03049423 PF-03049423 -
- Primary Outcome Measures
Name Time Method 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 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).
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.
- Secondary Outcome Measures
Name Time Method 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.
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.
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 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.
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).
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
Trial Locations
- Locations (70)
Spain Rehabilitation Center
🇺🇸Birmingham, Alabama, United States
Neurostudies, Inc.
🇺🇸Port Charlotte, Florida, United States
Norwood Nursing Center
🇺🇸Huntington, Indiana, United States
University Hospital
🇺🇸Birmingham, Alabama, United States
Jose Canedo, M.D., West Georgia Neurology
🇺🇸Columbus, Georgia, United States
Jagdish Sidhpura M.D.
🇺🇸Columbus, Georgia, United States
St. Francis Hospital
🇺🇸Columbus, Georgia, United States
The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
Rehabilitation Institute of St. Louis
🇺🇸St. Louis, Missouri, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Klinikum Altenburger Land
🇩🇪Altenburg, Germany
Severance Hospital, Yonsei University College of Medicine, Department of Neurology
🇰🇷Seoul, Korea, Republic of
Spaulding Rehabilitation Hospital
🇺🇸Boston, Massachusetts, United States
UNC HealthCare
🇺🇸Chapel Hill, North Carolina, United States
Universitaet Regensburg
🇩🇪Regensburg, Germany
Oklahoma University Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Asan Medical Center, Department of Neurology
🇰🇷Seoul, Korea, Republic of
Universitaetsklinikum Essen, Neurologische Klinik
🇩🇪Essen, Germany
Barnes-Jewish Hospital
🇺🇸St. Louis, Missouri, United States
Muscogee Manor & Rehabilitation Center
🇺🇸Columbus, Georgia, United States
Penn State Hershey Rehabilitation Hospital
🇺🇸Hummelstown, Pennsylvania, United States
The Methodist Hospital Neurological Institute
🇺🇸Houston, Texas, United States
Klinikum Rechts der Isar, Neurologische Klinik
🇩🇪Muenchen, Germany
Chonnam National University Hospital, Department of Neurology
🇰🇷Gwangju, Korea, Republic of
CHU Pellegrin
🇫🇷Bordeaux, France
CHU La Pitie Salpetriere
🇫🇷Paris Cedex 13, France
Wayne State University
🇺🇸Detroit, Michigan, United States
Investigational Drug Services at OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Medical Research & Health Education Foundation, Inc.
🇺🇸Columbus, Georgia, United States
Penn State Milton South Hershey Medical Center / Penn State College of Medicine
🇺🇸Hershey, Pennsylvania, United States
UNC Department of Neurology Stroke Division
🇺🇸Chapel Hill, North Carolina, United States
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Samsung Medical Center, Department of Neurology
🇰🇷Seoul, Korea, Republic of
Hallym University Sacred Heart Hospital, Department of Neurology
🇰🇷Anyang-si, Gyonggi-do, Korea, Republic of
Inha University Hospital, Department of Neurology
🇰🇷Incheon, Korea, Republic of
Massachusetts General Hospital/Department of Neurology
🇺🇸Boston, Massachusetts, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti
🇧🇬Pleven, Bulgaria
Broward Health North
🇺🇸Deerfield Beach, Florida, United States
Fawcett Memorial Hospital
🇺🇸Port Charlotte, Florida, United States
Neurologic Consultant, P.A.
🇺🇸Fort Lauderdale, Florida, United States
Parkview Hospital Randallia
🇺🇸Fort Wayne, Indiana, United States
Fort Wayne Neurological Center
🇺🇸Fort Wayne, Indiana, United States
Parkview Research Center
🇺🇸Fort Wayne, Indiana, United States
Parkview Regional Medical Center
🇺🇸Fort Wayne, Indiana, United States
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly
🇭🇺Budapest, Hungary
Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly
🇭🇺Gyor, Hungary
KEM Hospital
🇮🇳Pune, Maharashtra, India
Max Super Speciality Hospital
🇮🇳New Delhi, India
Seoul National University Bundang Hospital, Department of Neurology
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly
🇭🇺Balassagyarmat, Hungary
Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia
🇭🇺Budapest, Hungary
Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia
🇧🇬Sofia, Bulgaria
Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia
🇧🇬Sofia, Bulgaria
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czech Republic
MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti
🇧🇬Sofia, Bulgaria
MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya
🇧🇬Sofia, Bulgaria
MBAL Kaspela
🇧🇬Plovdiv, Bulgaria
UMBAL Tsaritsa Yoanna, Klinika po nevrologia
🇧🇬Sofia, Bulgaria
Fakultni nemocnice Plzen
🇨🇿Plzen - Lochotin, Czech Republic
Grey Nuns Community Hospital
🇨🇦Edmonton, Alberta, Canada
Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Semmelweis Egyetem AOK / Neurologiai Klinika
🇭🇺Budapest, Hungary
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Orszagos Idegtudomanyi Intezet, Stroke-ambulancia
🇭🇺Budapest, Hungary
Chang Gung Medical Foundation-Linkou Branch
🇨🇳Taoyuan County, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
OU Physicians Building
🇺🇸Oklahoma City, Oklahoma, United States