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

NCT01208233 | Terminated Phase 2 Results DMC

• 2 other identifiers: A95410042010-021414-32
• Study Type: interventional
• Target: 181
• Locations: 10 countries
• Sites: 70

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.

Conditions

Ischemic Stroke

Keywords

Phase 2 Ischemic stroke Safety and efficacy

Outcome Measures

Primary Outcomes (7)

• 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

• 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)

• 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

• 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

• 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

• 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)

• 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

Secondary Outcomes (17)

• Change From Baseline in Box and Blocks (B&B) Test at Day 90 for Paretic Hand (Part 2)

  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)

  Day 1 (Baseline), Day 90

• Change From Baseline in Hand Grip Strength Test at Day 90 for Paretic and Non-paretic Hands (Part 2)

  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)

  Day 1 (Baseline), Day 90

• Percentage of Participants With mRS (0-1) at Day 90 (Part 2)

  Day 90

Other Outcomes (5)

• All-cause Mortality (Part 2)

  The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.

• Mortality Directly Related to Stroke (Part 2)

  The time began from the participant provided informed consent through 28 calendar days post last administration of investigational product.

• Number of Participants With Neuro-worsening (Part 2)

  Day 1 (Baseline) up to Day 90

Study Arms (4)

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

Interventions

PF-03049423 DRUG

1 mg of PF-03049423 daily for 90 days

1 mg PF-03049423

Placebo OTHER

Placebo of PF-03049423 daily for 90 days

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Any other severe acute or chronic medical or psychiatric condition besides the stroke.
• Women of child bearing potential.
• Uncontrolled hypertension.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (70)

Spain Rehabilitation Center

Birmingham, Alabama, 35233, United States

Location

The Kirklin Clinic

Birmingham, Alabama, 35233, United States

Location

University Hospital

Birmingham, Alabama, 35294-3280, United States

Location

Broward Health North

Deerfield Beach, Florida, 33064, United States

Location

Neurologic Consultant, P.A.

Fort Lauderdale, Florida, 33308, United States

Location

Fawcett Memorial Hospital

Port Charlotte, Florida, 33952, United States

Location

Neurostudies, Inc.

Port Charlotte, Florida, 33952, United States

Location

Jagdish Sidhpura M.D.

Columbus, Georgia, 31901, United States

Location

Jose Canedo, M.D., West Georgia Neurology

Columbus, Georgia, 31904, United States

Location

St. Francis Hospital

Columbus, Georgia, 31904, United States

Location

Muscogee Manor & Rehabilitation Center

Columbus, Georgia, 31907, United States

Location

Medical Research & Health Education Foundation, Inc.

Columbus, Georgia, 31909, United States

Location

Parkview Hospital Randallia

Fort Wayne, Indiana, 46805, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46845, United States

Location

Parkview Regional Medical Center

Fort Wayne, Indiana, 46845, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

Norwood Nursing Center

Huntington, Indiana, 46750, United States

Location

Massachusetts General Hospital/Department of Neurology

Boston, Massachusetts, 02114, United States

Location

Spaulding Rehabilitation Hospital

Boston, Massachusetts, 02129, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Rehabilitation Institute of St. Louis

St Louis, Missouri, 63110, United States

Location

UNC HealthCare

Chapel Hill, North Carolina, 27514, United States

Location

UNC Department of Neurology Stroke Division

Chapel Hill, North Carolina, 27599-7025, United States

Location

Investigational Drug Services at OU Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

OU Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

OU Physicians Building

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State Milton South Hershey Medical Center / Penn State College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

Penn State Hershey Rehabilitation Hospital

Hummelstown, Pennsylvania, 17036, United States

Location

The Methodist Hospital Neurological Institute

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Voennomeditsinska Akademia - MBAL- Pleven, Otdelenie po Nervni bolesti

Pleven, 5800, Bulgaria

Location

MBAL Kaspela

Plovdiv, 4002, Bulgaria

Location

MBALNP "Sveti Naum" EAD, Klinika za Intenzivno Lechenie na Nervni Bolesti

Sofia, 1113, Bulgaria

Location

Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Otdelenie po Nevrologia

Sofia, 1202, Bulgaria

Location

MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya

Sofia, 1407, Bulgaria

Location

Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia

Sofia, 1431, Bulgaria

Location

UMBAL Tsaritsa Yoanna, Klinika po nevrologia

Sofia, 1527, Bulgaria

Location

Grey Nuns Community Hospital

Edmonton, Alberta, T6L 5X8, Canada

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 65691, Czechia

Location

Fakultni nemocnice Plzen

Plzen - Lochotin, 304 60, Czechia

Location

CHU Pellegrin

Bordeaux, 33076, France

Location

CHU La Pitie Salpetriere

Paris, 75651, France

Location

Klinikum Altenburger Land

Altenburg, 04600, Germany

Location

Universitaetsklinikum Essen, Neurologische Klinik

Essen, 45122, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum Rechts der Isar, Neurologische Klinik

München, 81675, Germany

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

Universitaet Regensburg

Regensburg, 93053, Germany

Location

Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly

Balassagyarmat, 2660, Hungary

Location

Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont/Neurologia

Budapest, 1076, Hungary

Location

Semmelweis Egyetem AOK / Neurologiai Klinika

Budapest, 1083, Hungary

Location

Honvedkorhaz-Allami Egeszsegugyi Kozpont, Ideggyogyaszati Osztaly

Budapest, 1134, Hungary

Location

Orszagos Idegtudomanyi Intezet, Stroke-ambulancia

Budapest, 1145, Hungary

Location

Petz Aladar Megyei Oktato Korhaz, Neurologiai Osztaly

Győr, 9024, Hungary

Location

KEM Hospital

Pune, Maharashtra, 411011, India

Location

Max Super Speciality Hospital

New Delhi, 110017, India

Location

Seoul National University Bundang Hospital, Department of Neurology

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Hallym University Sacred Heart Hospital, Department of Neurology

Anyang-si, Gyonggi-do, 431-070, South Korea

Location

Chonnam National University Hospital, Department of Neurology

Gwangju, 501-757, South Korea

Location

Inha University Hospital, Department of Neurology

Incheon, 400-711, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Severance Hospital, Yonsei University College of Medicine, Department of Neurology

Seoul, 120-752, South Korea

Location

Samsung Medical Center, Department of Neurology

Seoul, 135710, South Korea

Location

Asan Medical Center, Department of Neurology

Seoul, 138-736, South Korea

Location

Chang Gung Medical Foundation-Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Chang Gung Medical Foundation-Linkou Branch

Taoyuan, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 26738812 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Ischemic Stroke

Interventions

3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido(3,4-b)pyrazin-2(1H)-one

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

The study was terminated prematurely due to demonstrated futility at interim analysis. The final results are consistent with interim results.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: September 23, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 19, 2016
• Results First Posted: February 19, 2016

Record last verified: 2016-01

Locations

CA (1); IN (2); KR (8); TW (4); DE (6); HU (6); CZ (2); US (32); BU (7); FR (2)