Clinical trial NCT01208233: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ischemic Stroke
Keywords: Phase 2 Ischemic stroke Safety and efficacy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-09-23
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2)
timeFrame: Day 1 (Baseline) up to Day 90
measure: Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern (Part 1* and 2)
timeFrame: Day 1 (Baseline) up to follow-up (28 days after Day 90)
measure: Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern (Part 1* and 2)
timeFrame: Day 1 (Baseline) to Day 90
measure: Number of Participants With Significant Change in Physical Examination Findings (Part 1* and 2)
timeFrame: Day 1 (Baseline) up to Day 90
measure: Number of Participants With Significant Change in Neurological Examination Findings (Part 1* and 2)
timeFrame: Day 1 (Baseline) up to Day 90
measure: Number of Participants With Suicidal Behavior and/or Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Part 1* and 2)
timeFrame: Day 7 (Baseline) up to follow up (28 days after Day 90)
measure: Percentage of Participants With Modified Rankin Scale (mRS) Less Than or Equal to (<=2) at Day 90 (Part 2)
timeFrame: Day 90
Secondary outcomes:
measure: Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic Hand (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic and Non-paretic Hands (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic to Non-paretic Hand Ratio (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Percentage of Participants With mRS (0-1) at Day 90 (Part 2)
timeFrame: Day 90
measure: Percentage of Participants With National Institutes of Health Stroke Scale (NIHSS) (0-1) at Day 90 (Part 2)
timeFrame: Day 90
measure: Change From Baseline in NIHSS at Day 90 (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Percentage of Participants With Barthel Index (BI) >= 95 and BI =100 at Day 90 (Part 2)
timeFrame: Day 90
measure: BI at Day 90 (Part 2)
timeFrame: Day 90
measure: Domains of Interest: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding Sub Test at Day 90 (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Domains of Interest: Change From Baseline in RBANS Naming Sub Test at Day 90 (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: 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)
timeFrame: Day 1 (Baseline), Day 90
measure: Domains of Interest: Change From Baseline in Line Cancellation Test at Day 90 [(L-R)/(L+R)] (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Domains of Interest: Change From Baseline in Recognition Memory Test at Day 90 (Part 2)
timeFrame: Day 1 (Baseline), Day 90
measure: Gait Velocity Test at Day 90 (Part 2)
timeFrame: Day 90
measure: Plasma Concentrations of PF-03049423 (Part 1 and 2)
timeFrame: Days 1, 2, 7, 14, 30, 60 and 90
measure: Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Non-paretic Hand (Part 2)
timeFrame: Day 1 (Baseline), Day 90
Other outcomes:
measure: All-cause Mortality (Part 2)
timeFrame: The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.
measure: Mortality Directly Related to Stroke (Part 2)
timeFrame: The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.
measure: Number of Participants With Neuro-worsening (Part 2)
timeFrame: Day 1 (Baseline) up to Day 90
measure: 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)
timeFrame: Day 1 (Baseline) up to Day 14
measure: Treatment-emergent Adverse Events (AEs) Resulting in Discontinuation of Study Drug (Part 2)
timeFrame: Day 1 (Baseline) up to follow-up (28 days after Day 90)
Locations:
city: Birmingham
country: United States
facility: Spain Rehabilitation Center
state: Alabama
city: Birmingham
country: United States
facility: The Kirklin Clinic
state: Alabama
city: Birmingham
country: United States
facility: University Hospital
state: Alabama
city: Deerfield Beach
country: United States
facility: Broward Health North
state: Florida
city: Fort Lauderdale
country: United States
facility: Neurologic Consultant, P.A.
state: Florida
city: Port Charlotte
country: United States
facility: Fawcett Memorial Hospital
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies, Inc.
state: Florida
city: Columbus
country: United States
facility: Jagdish Sidhpura M.D.
state: Georgia
city: Columbus
country: United States
facility: Jose Canedo, M.D., West Georgia Neurology
state: Georgia
city: Columbus
country: United States
facility: St. Francis Hospital
state: Georgia
city: Columbus
country: United States
facility: Muscogee Manor & Rehabilitation Center
state: Georgia
city: Columbus
country: United States
facility: Medical Research & Health Education Foundation, Inc.
state: Georgia
city: Fort Wayne
country: United States
facility: Parkview Hospital Randallia
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Regional Medical Center
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Huntington
country: United States
facility: Norwood Nursing Center
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital/Department of Neurology
state: Massachusetts
city: Boston
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: St. Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: St. Louis
country: United States
facility: Rehabilitation Institute of St. Louis
state: Missouri
city: Chapel Hill
country: United States
facility: UNC HealthCare
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Department of Neurology Stroke Division
state: North Carolina
city: Oklahoma City
country: United States
facility: Investigational Drug Services at OU Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma University Health Sciences Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: OU Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: OU Physicians Building
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Milton South Hershey Medical Center / Penn State College of Medicine
state: Pennsylvania
city: Hummelstown
country: United States
facility: Penn State Hershey Rehabilitation Hospital
state: Pennsylvania
city: Houston
country: United States
facility: The Methodist Hospital Neurological Institute
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Pleven
country: Bulgaria
facility: Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti
city: Plovdiv
country: Bulgaria
facility: MBAL Kaspela
city: Sofia
country: Bulgaria
facility: MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti
city: Sofia
country: Bulgaria
facility: Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia
city: Sofia
country: Bulgaria
facility: MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya
city: Sofia
country: Bulgaria
facility: Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia
city: Sofia
country: Bulgaria
facility: UMBAL Tsaritsa Yoanna, Klinika po nevrologia
city: Edmonton
country: Canada
facility: Grey Nuns Community Hospital
state: Alberta
city: Brno
country: Czech Republic
facility: Fakultni nemocnice u sv. Anny v Brne
city: Plzen - Lochotin
country: Czech Republic
facility: Fakultni nemocnice Plzen
city: Bordeaux
country: France
facility: CHU Pellegrin
city: Paris Cedex 13
country: France
facility: CHU La Pitie Salpetriere
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land
city: Essen
country: Germany
facility: Universitaetsklinikum Essen, Neurologische Klinik
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Muenchen
country: Germany
facility: Klinikum Rechts der Isar, Neurologische Klinik
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Regensburg
country: Germany
facility: Universitaet Regensburg
city: Balassagyarmat
country: Hungary
facility: Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia
city: Budapest
country: Hungary
facility: Semmelweis Egyetem AOK / Neurologiai Klinika
city: Budapest
country: Hungary
facility: Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly
city: Budapest
country: Hungary
facility: Orszagos Idegtudomanyi Intezet, Stroke-ambulancia
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly
city: Pune
country: India
facility: KEM Hospital
state: Maharashtra
city: New Delhi
country: India
facility: Max Super Speciality Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital, Department of Neurology
state: Gyeonggi-do
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital, Department of Neurology
state: Gyonggi-do
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital, Department of Neurology
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital, Department of Neurology
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University College of Medicine, Department of Neurology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Department of Neurology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Department of Neurology
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.