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

Terminated

Phase 2 Results

Trial Description

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.

Trial Stopped: See termination reason in detailed description.

Conditions

Interventions

  • Placebo Drug
    Intervention Desc: Placebo of PF-03049423 daily for 90 days
    ARM 1: Kind: Experimental
    Label: Placebo
  • PF-03049423 Drug
    Intervention Desc: 6 mg of PF-03049423 daily for 90 days
    ARM 1: Kind: Experimental
    Label: 1 mg PF-03049423
    ARM 2: Kind: Experimental
    Label: 3 mg of PF-03049423
    ARM 3: Kind: Experimental
    Label: 6 mg of PF-03049423

Trial Design

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

Outcomes

Type Measure Time Frame Safety Issue
Primary Safety and tolerability assessed by an Independent Data and Safety Monitoring Board (DSMB) using data, including SAEs, AEs , vital signs, brain MRI, ECG, physical (including neurological) examination, NIHSS scores, laboratory tests. Day 14 Yes
Primary Proportion of subjects with Modified Rankin Scale (mRS) less than or equal to 2 Day 90 No
Secondary Plasma concentrations of PF-03049423 Day 90 No
Secondary Box and Blocks, Hand Grip Strength Test Day 90 No
Secondary Proportion of subjects with: mRS (0-1), NIHSS (0-1), NIHSS, BI, BI greater or equal to 95 and BI =100 Day 90 No
Secondary Domains of Interest: RBANS Coding Sub Test, RBANS Naming Sub Test, Line Cancellation, Recognition Memory Test Day 90 No
Secondary Gait Velocity Day 90 No
Primary Number of Participants With Any Abnormal Laboratory Test Results (Part 1* and 2) 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) 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) Day 1 (Baseline) to Day 90 Yes
Primary Number of Participants With Significant Change in Physical Examination Findings (Part 1* and 2) Day 1 (Baseline) up to Day 90 Yes
Primary Number of Participants With Significant Change in Neurological Examination Findings (Part 1* and 2) 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) 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) Day 90 No
Secondary Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic Hand (Part 2) 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) 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) 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) Day 1 (Baseline), Day 90 No
Secondary Percentage of Participants With mRS (0-1) at Day 90 (Part 2) Day 90 No
Secondary Percentage of Participants With National Institutes of Health Stroke Scale (NIHSS) (0-1) at Day 90 (Part 2) Day 90 Yes
Secondary Change From Baseline in NIHSS at Day 90 (Part 2) Day 1 (Baseline), Day 90 Yes
Secondary Percentage of Participants With Barthel Index (BI) >= 95 and BI =100 at Day 90 (Part 2) Day 90 No
Secondary BI at Day 90 (Part 2) 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) Day 1 (Baseline), Day 90 No
Secondary Domains of Interest: Change From Baseline in RBANS Naming Sub Test at Day 90 (Part 2) 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) 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) Day 1 (Baseline), Day 90 No
Secondary Domains of Interest: Change From Baseline in Recognition Memory Test at Day 90 (Part 2) Day 1 (Baseline), Day 90 No
Secondary Gait Velocity Test at Day 90 (Part 2) 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) Day 1 (Baseline), Day 90 No

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