Ischemic StrokePhase 2NCT01208233
Study Evaluating The Safety And Efficacy Of PF-03049423 In Subjects With Ischemic Stroke
A Phase 2 study testing PF-03049423 in people with Ischemic Stroke, run by Pfizer at 70 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- PF-03049423
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 181 participants
- Where
- 70 sitesin 10 countries
- Study dates
- Dec 2010to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Any other severe acute or chronic medical or psychiatric condition besides the stroke.
- Women of child bearing potential.
- Uncontrolled hypertension.
Trial locations and contacts
70 sites in 10 countries.
70 sites in 10 countries
United States32 sites
Spain Rehabilitation Center
Birmingham, Alabama, 35233
The Kirklin Clinic
Birmingham, Alabama, 35233
University Hospital
Birmingham, Alabama, 35294-3280
Massachusetts General Hospital/Department of Neurology
Boston, Massachusetts, 02114
Spaulding Rehabilitation Hospital
Boston, Massachusetts, 02129
UNC HealthCare
Chapel Hill, North Carolina, 27514
UNC Department of Neurology Stroke Division
Chapel Hill, North Carolina, 27599-7025
Jagdish Sidhpura M.D.
Columbus, Georgia, 31901
Jose Canedo, M.D., West Georgia Neurology
Columbus, Georgia, 31904
St. Francis Hospital
Columbus, Georgia, 31904
Muscogee Manor & Rehabilitation Center
Columbus, Georgia, 31907
Medical Research & Health Education Foundation, Inc.
Columbus, Georgia, 31909
Broward Health North
Deerfield Beach, Florida, 33064
Wayne State University
Detroit, Michigan, 48201
Neurologic Consultant, P.A.
Fort Lauderdale, Florida, 33308
Parkview Hospital Randallia
Fort Wayne, Indiana, 46805
Fort Wayne Neurological Center
Fort Wayne, Indiana, 46845
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845
Parkview Research Center
Fort Wayne, Indiana, 46845
Penn State Milton South Hershey Medical Center / Penn State College of Medicine
Hershey, Pennsylvania, 17033
The Methodist Hospital Neurological Institute
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
Penn State Hershey Rehabilitation Hospital
Hummelstown, Pennsylvania, 17036
Norwood Nursing Center
Huntington, Indiana, 46750
Investigational Drug Services at OU Medical Center
Oklahoma City, Oklahoma, 73104
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, 73104
OU Medical Center
Oklahoma City, Oklahoma, 73104
OU Physicians Building
Oklahoma City, Oklahoma, 73104
Fawcett Memorial Hospital
Port Charlotte, Florida, 33952
Neurostudies, Inc.
Port Charlotte, Florida, 33952
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Rehabilitation Institute of St. Louis
St Louis, Missouri, 63110
South Korea8 sites
Hallym University Sacred Heart Hospital, Department of Neurology
Anyang-si, Gyonggi-do, 431-070
Chonnam National University Hospital, Department of Neurology
Gwangju, 501-757
Inha University Hospital, Department of Neurology
Incheon, 400-711
Seoul National University Bundang Hospital, Department of Neurology
Seongnam-si, Gyeonggi-do, 463-707
Seoul National University Hospital
Seoul, 110-744
Severance Hospital, Yonsei University College of Medicine, Department of Neurology
Seoul, 120-752
Samsung Medical Center, Department of Neurology
Seoul, 135710
Asan Medical Center, Department of Neurology
Seoul, 138-736
Bulgaria7 sites
Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti
Pleven, 5800
MBAL Kaspela
Plovdiv, 4002
MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti
Sofia, 1113
Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia
Sofia, 1202
MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya
Sofia, 1407
Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia
Sofia, 1431
UMBAL Tsaritsa Yoanna, Klinika po nevrologia
Sofia, 1527
Germany6 sites
Klinikum Altenburger Land
Altenburg, 04600
Universitaetsklinikum Essen, Neurologische Klinik
Essen, 45122
Universitaetsklinikum Leipzig
Leipzig, 04103
Klinikum Rechts der Isar, Neurologische Klinik
München, 81675
Universitaetsklinikum Muenster
Münster, 48149
Universitaet Regensburg
Regensburg, 93053
Hungary6 sites
Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly
Balassagyarmat, 2660
Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia
Budapest, 1076
Semmelweis Egyetem AOK / Neurologiai Klinika
Budapest, 1083
Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly
Budapest, 1134
Orszagos Idegtudomanyi Intezet, Stroke-ambulancia
Budapest, 1145
Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly
Győr, 9024
Taiwan4 sites
Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 833
China Medical University Hospital
Taichung, 404
National Taiwan University Hospital
Taipei, 100
Chang Gung Medical Foundation-Linkou Branch
Taoyuan County, 333
Czechia2 sites
Fakultni nemocnice u sv. Anny v Brne
Brno, 65691
Fakultni nemocnice Plzen
Plzen - Lochotin, 304 60
France2 sites
CHU Pellegrin
Bordeaux, 33076
CHU La Pitie Salpetriere
Paris, 75651
India2 sites
Max Super Speciality Hospital
New Delhi, 110017
KEM Hospital
Pune, Maharashtra, 411011
About this study
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
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.
Read the 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.
- Conditions
- Ischemic Stroke
- Being tested
- PF-03049423, Placebo
- Keywords
- Phase 2 Ischemic stroke Safety and efficacy
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-03049423Drug
1 mg of PF-03049423 daily for 90 days
PF-03049423Drug
3 mg of PF-03049423 daily for 90 days
PF-03049423Drug
6 mg of PF-03049423 daily for 90 days
PlaceboOther
Placebo of PF-03049423 daily for 90 days
| Study group | Role | What they receive |
|---|---|---|
| 1 mg PF-03049423 | Experimental | Not described Receives: Drug: PF-03049423 |
| 3 mg of PF-03049423 | Experimental | Not described Receives: Drug: PF-03049423 |
| 6 mg of PF-03049423 | Experimental | Not described Receives: Drug: PF-03049423 |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 (Baseline) up to Day 90
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.
Measured: Day 1 (Baseline) up to follow-up (28 days after Day 90)
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.
Measured: Day 1 (Baseline) to Day 90
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.
Measured: Day 1 (Baseline) up to Day 90
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.
Measured: Day 1 (Baseline) up to Day 90
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.
Measured: Day 7 (Baseline) up to follow up (28 days after Day 90)
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).
Measured: Day 90
Secondary outcomes (17)
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 1 (Baseline), Day 90
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).
Measured: Day 90
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.
Measured: Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 90
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.
Measured: Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 1 (Baseline), Day 90
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.
Measured: Day 90
Plasma Concentrations of PF-03049423 (Part 1 and 2)
Measured: 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)
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.
Measured: Day 1 (Baseline), Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2010 (estimated)
- Study startDec 2010
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01208233
- Sponsor's protocol ID
- A9541004
- Other IDs
- 2010-021414-32
- Status last verified
- Jan 2016
- First submitted
- 22 Sep 2010
- Last updated
- 19 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26738812
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01208233
- Acronym / sponsor ID
- A9541004
- Conditions
- Ischemic Stroke
- Keywords
- Phase 2 Ischemic stroke Safety and efficacy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 181 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 23 Sep 2010 (estimated)
- Results
- Posted 19 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 mg PF-03049423 | Experimental | Drug: PF-03049423 |
| 3 mg of PF-03049423 | Experimental | Drug: PF-03049423 |
| 6 mg of PF-03049423 | Experimental | Drug: PF-03049423 |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- Any other severe acute or chronic medical or psychiatric condition besides the stroke.
- Women of child bearing potential.
- Uncontrolled hypertension.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-030494231 mg of PF-03049423 daily for 90 days | Drug | 1 mg PF-03049423 |
| PF-030494233 mg of PF-03049423 daily for 90 days | Drug | 3 mg of PF-03049423 |
| PF-030494236 mg of PF-03049423 daily for 90 days | Drug | 6 mg of PF-03049423 |
| PlaceboPlacebo of PF-03049423 daily for 90 days | Other | Placebo |
Primary outcome
Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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).
17 secondary outcomes
Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic Hand (Part 2)
Time frame: Day 1 (Baseline), Day 90
Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2)
Time frame: Day 1 (Baseline), Day 90
Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic and Non-paretic Hands (Part 2)
Time frame: Day 1 (Baseline), Day 90
Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2)
Time frame: Day 1 (Baseline), Day 90
Percentage of Participants With mRS (0-1) at Day 90 (Part 2)
Time frame: Day 90
Percentage of Participants With National Institutes of Health Stroke Scale (NIHSS) (0-1) at Day 90 (Part 2)
Time frame: Day 90
Change From Baseline in NIHSS at Day 90 (Part 2)
Time frame: Day 1 (Baseline), Day 90
Percentage of Participants With Barthel Index (BI) >= 95 and BI =100 at Day 90 (Part 2)
Time frame: Day 90
BI at Day 90 (Part 2)
Time frame: Day 90
Domains of Interest: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding Sub Test at Day 90 (Part 2)
Time frame: Day 1 (Baseline), Day 90
Domains of Interest: Change From Baseline in RBANS Naming Sub Test at Day 90 (Part 2)
Time frame: Day 1 (Baseline), Day 90
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)
Time frame: Day 1 (Baseline), Day 90
Domains of Interest: Change From Baseline in Line Cancellation Test at Day 90 [(L-R)/(L+R)] (Part 2)
Time frame: Day 1 (Baseline), Day 90
Domains of Interest: Change From Baseline in Recognition Memory Test at Day 90 (Part 2)
Time frame: Day 1 (Baseline), Day 90
Gait Velocity Test at Day 90 (Part 2)
Time frame: Day 90
Plasma Concentrations of PF-03049423 (Part 1 and 2)
Time frame: 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)
Time frame: Day 1 (Baseline), Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26738812Di 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
70 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-03049423 in people with Ischemic Stroke, run by Pfizer at 70 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 70 sites in United States, South Korea, Bulgaria, Germany, Hungary and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2) (time frame: Day 1 (Baseline) up to Day 90). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01208233, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2016.