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

Ischemic Stroke Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01208233
• Other study ID #: A9541004
• Secondary ID: 2010-021414-32
• Status: Terminated
• Phase: Phase 2
• First received: September 22, 2010
• Last updated: January 22, 2016
• Start date: December 2010
• Est. completion date: December 2013

Study information

• Verified date: January 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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. The study will also explore the relationship between PF-03049423 concentration and blood pressure.

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 information / eligibility

• Status: Terminated
• Enrollment: 181
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• PF-03049423
1 mg of PF-03049423 daily for 90 days
• PF-03049423
3 mg of PF-03049423 daily for 90 days
• PF-03049423
6 mg of PF-03049423 daily for 90 days

Other:
• Placebo
Placebo of PF-03049423 daily for 90 days

Locations

Country	Name	City	State
Bulgaria	Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti	Pleven
Bulgaria	MBAL Kaspela	Plovdiv
Bulgaria	MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya	Sofia
Bulgaria	MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti	Sofia
Bulgaria	UMBAL Tsaritsa Yoanna, Klinika po nevrologia	Sofia
Bulgaria	Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia	Sofia
Bulgaria	Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia	Sofia
Canada	Grey Nuns Community Hospital	Edmonton	Alberta
Czech Republic	Fakultni nemocnice u sv. Anny v Brne	Brno
Czech Republic	Fakultni nemocnice Plzen	Plzen - Lochotin
France	CHU Pellegrin	Bordeaux
France	CHU La Pitie Salpetriere	Paris Cedex 13
Germany	Klinikum Altenburger Land	Altenburg
Germany	Universitaetsklinikum Essen, Neurologische Klinik	Essen
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Klinikum Rechts der Isar, Neurologische Klinik	Muenchen
Germany	Universitaetsklinikum Muenster	Muenster
Germany	Universitaet Regensburg	Regensburg
Hungary	Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly	Balassagyarmat
Hungary	Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia	Budapest
Hungary	Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly	Budapest
Hungary	Orszagos Idegtudomanyi Intezet, Stroke-ambulancia	Budapest
Hungary	Semmelweis Egyetem AOK / Neurologiai Klinika	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly	Gyor
India	Max Super Speciality Hospital	New Delhi
India	KEM Hospital	Pune	Maharashtra
Korea, Republic of	Hallym University Sacred Heart Hospital, Department of Neurology	Anyang-si	Gyonggi-do
Korea, Republic of	Chonnam National University Hospital, Department of Neurology	Gwangju
Korea, Republic of	Inha University Hospital, Department of Neurology	Incheon
Korea, Republic of	Seoul National University Bundang Hospital, Department of Neurology	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center, Department of Neurology	Seoul
Korea, Republic of	Samsung Medical Center, Department of Neurology	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University College of Medicine, Department of Neurology	Seoul
Taiwan	Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch	Taoyuan County
United States	Spain Rehabilitation Center	Birmingham	Alabama
United States	The Kirklin Clinic	Birmingham	Alabama
United States	University Hospital	Birmingham	Alabama
United States	Massachusetts General Hospital/Department of Neurology	Boston	Massachusetts
United States	Spaulding Rehabilitation Hospital	Boston	Massachusetts
United States	UNC Department of Neurology Stroke Division	Chapel Hill	North Carolina
United States	UNC HealthCare	Chapel Hill	North Carolina
United States	Jagdish Sidhpura M.D.	Columbus	Georgia
United States	Jose Canedo, M.D., West Georgia Neurology	Columbus	Georgia
United States	Medical Research & Health Education Foundation, Inc.	Columbus	Georgia
United States	Muscogee Manor & Rehabilitation Center	Columbus	Georgia
United States	St. Francis Hospital	Columbus	Georgia
United States	Broward Health North	Deerfield Beach	Florida
United States	Wayne State University	Detroit	Michigan
United States	Neurologic Consultant, P.A.	Fort Lauderdale	Florida
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Penn State Milton South Hershey Medical Center / Penn State College of Medicine	Hershey	Pennsylvania
United States	The Methodist Hospital	Houston	Texas
United States	The Methodist Hospital Neurological Institute	Houston	Texas
United States	Penn State Hershey Rehabilitation Hospital	Hummelstown	Pennsylvania
United States	Norwood Nursing Center	Huntington	Indiana
United States	Investigational Drug Services at OU Medical Center	Oklahoma City	Oklahoma
United States	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma
United States	OU Medical Center	Oklahoma City	Oklahoma
United States	OU Physicians Building	Oklahoma City	Oklahoma
United States	Fawcett Memorial Hospital	Port Charlotte	Florida
United States	Neurostudies, Inc.	Port Charlotte	Florida
United States	Barnes-Jewish Hospital	St. Louis	Missouri
United States	Rehabilitation Institute of St. Louis	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czech Republic,  France,  Germany,  Hungary,  India,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-cause Mortality (Part 2)	Deaths regardless causality were reported.	The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.	Yes
Other	Mortality Directly Related to Stroke (Part 2)	Deaths caused by stroke were reported.	The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.	Yes
Other	Number of Participants With Neuro-worsening (Part 2)	NIHSS change of 4 points or greater.	Day 1 (Baseline) up to Day 90	Yes
Other	Number of Participants With SBP <100 mm Hg or SBP Decline >=30 mm Hg From Immediate Pre-dose Measurement, With or Without Neuro-worsening (Defined as an NIHSS Increase of 4 Points or Greater) Within 2 Hours Post-dose (Part 2)		Day 1 (Baseline) up to Day 14	Yes
Other	Treatment-emergent Adverse Events (AEs) Resulting in Discontinuation of Study Drug (Part 2)	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.	Day 1 (Baseline) up to follow-up (28 days after Day 90)	Yes
Primary	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.	Day 1 (Baseline) up to Day 90	Yes
Primary	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.	Day 1 (Baseline) up to follow-up (28 days after Day 90)	Yes
Primary	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.	Day 1 (Baseline) to Day 90	Yes
Primary	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.	Day 1 (Baseline) up to Day 90	Yes
Primary	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.	Day 1 (Baseline) up to Day 90	Yes
Primary	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.	Day 7 (Baseline) up to follow up (28 days after Day 90)	Yes
Primary	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).	Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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).	Day 90	No
Secondary	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.	Day 90	Yes
Secondary	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.	Day 1 (Baseline), Day 90	Yes
Secondary	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.	Day 90	No
Secondary	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.	Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No
Secondary	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.	Day 90	No
Secondary	Plasma Concentrations of PF-03049423 (Part 1 and 2)		Days 1, 2, 7, 14, 30, 60 and 90	No
Secondary	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.	Day 1 (Baseline), Day 90	No

External Links

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