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.
A Double Blind (3rd Party Open), Randomized, Placebo Controlled, Parallel Group, Multiple Dose Escalation Study To Evaluate The Safety, Toleration, Pharmacokinetics Of PF-03049423 In Healthy Young Adult Volunteers And Healthy Elderly Volunteers
The purpose this study is to evaluate the safety and toleration of PF-03049423 following multiple dose administration as an oral solution to healthy young adult volunteers and healthy elderly volunteers. The study will also evaluate the pharmacokinetics of PF-03049423 after multiple dose administration to healthy young adult volunteers and healthy elderly volunteers. The study will also explore the relationship between blood pressure (supine and standing) and PF-03049423 concentration.
2016-03-01·Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association4区 · 医学
Phosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial.
4区 · 医学
作者: Franco Di Cesare ; Jessica Mancuso ; Phil Woodward ; Martin M Bednar ; Peter T Loudon ; A9541004 Stroke Study Group
The therapeutic potential of phosphodiesterase-5 inhibitor PF-03049423 was evaluated in a phase 2, multicenter, randomized, double-blind, placebo-controlled study of subjects with acute ischemic stroke (
Subjects (N = 70) received PF-03049423 6 mg (or placebo, N = 67) once daily, orally, commencing between 24 and 78 hours of stroke onset, and continuing for 90 days. Postbaseline efficacy assessments were performed on Days 7, 14, 30, 60, and 90. Modified Rankin Scale (mRS), Barthel Index, National Institutes of Health Stroke Scale, Box and Blocks Test, Hand-Grip Strength Test, 10-Meter Walk Test, Repeatable Battery Assessment of Neuropsychological Status Naming and Coding Subtests, Line Cancellation Test, and Recognition Memory Test were administered to evaluate poststroke recovery. The primary endpoint was the mRS responder rate (score 0-2 at Day 90). The study included a planned interim analysis of efficacy data.
The primary efficacy analysis using logistic regression showed no statistically significant difference between PF-03049423 6 mg and placebo (responder rate of 42.6% and 46.2%, respectively). Although PF-03049423 showed a satisfactory safety and tolerability profile, no signal of efficacy emerged from any of the outcome measures.
PF-03049423 showed no therapeutic potential for acute ischemic stroke.
Innovations in clinical neuroscience
Assessment of Cognitive and Neurologic Recovery in Ischemic Stroke Drug Trials: Results from a Randomized, Double-blind, Placebo-controlled Study.
作者: Franco Di Cesare ; Jessica Mancuso ; Brian Silver ; Peter T Loudon
Objective. Ischemic stroke is a serious medical condition with limited therapeutic options. The evaluation of the therapeutic potential of novel pharmacological interventions is carried-out in Phase II trials. The study design, primarily intended to evaluate efficacy and safety, is a balance between utilizing as few patients as possible to minimize safety risk and enrolling sufficient patients to detect unambiguous efficacy signals. We sought to determine whether post-stroke recovery outcomes based on behavioral measures of cognitive and motor impairment yielded additional information beyond that of clinician-based methods. Design. This was a multicenter, multinational, randomized, parallel group, controlled versus placebo, efficacy, and safety study of PF-03049423 for treatment of acute ischemic stroke. Settings and participants. Our study subjects were acute ischemic stroke inpatients. Measurements. Outcome measures were derived from rating scales (Modified Rankin Scale, Barthel Index, and National Institutes of Health Stroke Scale) and behavioral tests (Box and Blocks Test, Hand Grip Strength Test, 10-Meter Walk Test, Repeatable Battery Assessment of Neuropsychological Status Naming and Coding Subtests, Line Cancellation Test, and Recognition Memory Test). Assessments were performed at Days 7, 14, 30, 60, and 90. Post-hoc analyses of correlations among the outcome measures at each measurement time point on a cohort of 137 subjects were conducted. Results. Results support the validity of measures from Box and Blocks Test, Hand Grip Strength Test, 10-Meter Walk Test, and Repeatable Battery Assessment of Neuropsychological Status Coding Subtests to monitor post-stroke recovery in clinical trial settings. Notably, the Recognition Memory Test did not show a correlation with the Modified Rankin Scale, and, in fact, did not show improvement over time. Conclusion. The behavioral measures of cognitive and motor functions included in this study may extend the evaluation of the therapeutic potential of new treatments for stroke recovery. The lack of correlation between Recognition Memory Test and the traditional efficacy endpoints, at least in part due to absence of any improvement in recognition memory, suggests that there may be cognitive elements not detected by the Modified Rankin Scale. This is clinically relevant and memory improvement has potential as an endpoint in future trials aiming to improve certain aspects of cognition.