Open AccessPhase II Studies of the Glycine Antagonist GV150526 in Acute Stroke
Author(s) -
Principal Investigator Viken Babikian,
MD; Coordinator Eloise Licata-Gehr,
Michele Joseph,
Asmaa Namoos,
Peter Bailey,
Mwj MacDougall,
M. Maclean,
MargaretJ . Wheelock,
MD; G. Kolyvas,
Principal Investigator Thomas Banas,
MD; Coordinator Mary Ann Wissman,
Brian Porter,
Mamatha Bhat,
MD; Paul E. Later,
MD; Stanley D. Wissman,
Mary Ottinger,
Martin J. Stevens,
Allan Plant,
Paul Chang,
Patrick G. Beatty,
M Beatty,
Michael Vasquez,
Matthias Schmidt,
ML Allen,
Principal Investigator Andre Bellavance,
Patricia R. Hebert,
Regina Berger,
MD; R. Filatrault,
MD; Z. Nasredding,
Mark Trottier,
M. Duplessis,
MD; F. Grand Maison,
M. Ninković,
Peter H. Berman,
M. Miskin,
FACS; Stephen A. Shaivitz,
M. Reich,
Principal Investigator Oscar Benavente,
Mark Bruce,
MSN; Sub-Investigators Diane Solomen,
Morris Sherman,
Mary M. Hart,
MD; Merrill Kanter-Carolin,
Mary M. LaLonde,
Michaela Rogers,
Robert M. Bruce,
MSN; Ann Leonard,
BSN.,
Principal Investigator Thomas Brott,
Mary E. Spilker,
Raymond Broderick,
Rashmi Kothari,
MD; Arthur Pancioli,
MD; Laura Sauerbeck,
Ross A. Miller,
RN,
Patricia Clark,
MD; Coordinators Sandy McClurksey Deely,
Robert S. Fisher,
RN; Sub-Investigators Helmi Lutsep,
MD; Jennifer Quinn,
Michael Crawford,
M. Egan,
Mark E. Nesbit,
MD; AbdulKader Al-Azzaz,
Peter Earley,
Marie Herr,
R. Michel,
MD; Gretchen Dike,
MD; Nicholas Maragakis,
Michael Polydefkis,
Marlis Wagner,
M. Wang,
MD; Renata Rusa,
Michelle L. Jones,
M. G. Kerr,
MD; Lauren Moo,
M. C. Pardo,
Michael Silverman,
Maurice Hoffman,
DO; Ellen Diebert,
MD; Hyder Jinnah,
Mary York,
M. Hoke,
MD; Francisco Vega-Bermudez,
Marcello Comi,
Matthew B. Hillis,
Michael Rich,
Paul R. Ervin,
Meagan Kelley,
MD; Michael F. Perll,
Maggie Box,
M. Robles,
MD; Jay S. Zwibelman,
MD; Donald K. Hopewell,
Monique M. Ryan,
Michael F. Wendland,
Principal Investigator William Feinberg,
MD; Bruce Coull,
MD; Coordinator Diane Rose-Taylor,
R. A’Hern,
Melissa Anderson,
M Keim,
MD; Diane Rose-Taylor,
CCRN.,
Patty Haley,
Michael J. Morris,
Richard Johnston,
MD; Nina Solenski,
Mark A. Nathan,
MD; Thomas Bleck,
Matthew Worrall,
MD; Dave Leszczyszyn,
Mitzi K. Hemstreet,
Maria X. Kiely,
Marcelline Burns,
M. Klein,
MD; Wayne Cail,
M W Huff,
Megan Armstrong,
Mariano Provencio,
M. T. Snider,
MD; Jay Van Gerpen,
PingI Hsu,
Marcus Duke,
RN; Gerry Banet,
B. Choi,
M. Lee,
MD; Ted Lowenkopf,
P.A. Innes,
Min Huang,
MD; C. Rumball,
Marvin J. Miller,
MD; J. Haegert,
M Holmes,
MD; B. Oldring,
Michele Macnab,
MD; R. Grosch,
Mark Deady,
Matthew Street,
Mary O’Brien,
MD; L. Vertesi,
Matthias Erhardt,
MD; J. Finkler,
Michael J. Tessler,
Michele Glazer,
Michael D. Noseworthy,
MD; M. Knazen,
Madeline MacDonald,
Michael B. Smyth,
Principal Investigator Jeffrey Karp,
M. Phillips,
Robert J. Spiegel,
M. Bowman,
MD; James P. Hampsey,
Manhal Habib,
R. Jason Schroeder,
RN; Kim Stopnytsky,
Lpn,
Ccrc Ccrc,
Principal Investigator Andrew Kertecz,
M. J. Cooper,
Patrick D. Lyden,
MD; Coordinator Karen Rapp,
Christopher Jackson,
Matthew J. Ellis,
Pamela Noack,
Marwan Sabbagh,
MD; Douglas Galasko,
Per-Olov Rapp,
Robert G. Kelly,
Robert Blake Werner,
Rin Chang,
Pamela J. Morris,
MD; Coordinator Susan Pusek; Sub-Investigators Albert Hinn,
Mary John,
Martine Bernard,
Peter Phillips,
Mbbs,
Fiona Reidy,
RN; Sub-Investigators G. Gubitz,
MD; F. Tanha,
MD; R. Leckey,
Mark Ansell,
MD; S. Darvesh,
Mónica Aguilar,
Patrick Pullicino,
Matthew Starr,
RN; Sub-Investigator Frederick E. Munschauer,
Iii ~,
Philip E. Ross,
Mark C. Norris,
Christian Steinberg,
MD; Bruce Zaret,
Manoj Maniar,
Norris Mc,
Crc Crc,
Paul Sacco,
MD; Coordinators Bernadette Boden-Albala,
Marta Jiménez,
Michael Möhr,
M. Kargman,
M. Marshall,
Mitch Elkind,
Mary B. Roberts,
M. Gan,
Michael Shipley,
MD; Sami Aboumatar,
Maslyn A Greene,
Principal Investigator A. Shuaib,
MD; Coordinator E. Kadribasic,
Robert D. Keegan,
M. Kathleen Stewart,
MD; K. Khaan,
Principal Investigator Ashfaq Shuaib,
MD; Coordinator Traci Renee Dean,
Russell S. Richardson,
Mehran Moussavian,
MD; Wiaam Faloriji,
Mark Johnson,
Mark Levin,
Principal Investigator Scott Silliman,
MD; Coordinator Paula S. Fuqua,
Pierre Berger,
Marc Najjar,
Marianne Schwartz,
Paul R. Solomon,
María Luisa Limón,
Robert G. Hart,
MD; Merrill C. Kanter Carolin,
M. Benavente,
Principal Investigator Sidney Starkman,
Mirjam Schubert,
MPH; Sub-Investigators Bruce Dobkin,
MD; Jeffrey Saver,
Marta Vespa,
M Alger,
; Phd,
Philip Teitelbaùm,
M Robillard,
MD; J. Lachapelle,
Michel A. Boileau,
Marie Rousseau,
Monica Roy,
Marc-André Laplante,
Principal Investigator Stephen Thurston,
M. Lutz,
CNS; Sub-Investigators F.E. McGee,
Marion Harris,
Matthew White,
MD; J.M. O’Ban,
Mary Brush,
Maxime C. Cohen,
MD; T.A. Smith,
Mary Mathe,
Max Karner,
Michael Worthington,
Michael D. Deel,
Peter C.Y. Tong,
Márta Hock,
Matthias Albers,
MD; Andrew Woofenden,
Midori A. Yenari,
MD; Susan Freyberg,
MS; Grayce Guro,
Raymond J. Hock,
. Ms,
Principal Investigator Stanley Tuhrim,
Mathew M. Augustine,
Ronit Weinberger,
MD; Deborah Horowitz,
MD; Kara Sheinart,
Marleen Schonewille,
Michel Atlas,
Pedro Rigueiro Veloso,
MD; Coordinator Marilyn Reid; Sub-Investigators K. Adaikari,
Mark C. Gebhardt,
Murali Nair,
P Wang,
Douglas R. McLean,
M. J. Arun Kumar,
MD; Dennis Garwacki,
Manohar Roda,
David Hui,
PhD; Jenny Coyner,
CTC; David Vrabel,
CRC; Deb Honings,
Rebecca Rose,
Cnrn,
MS; Robert Sladana,
D Pharm,
Principal Investigator Larry Wechsler,
MD; Coordinator Laurel Yasko,
R Knepper,
Marika Massaro,
Cat Graham,
Mary E. Larkin,
MD; Thomas Ulicny,
MD; Howard Yonas,
MD; Carol Barch,
ChunHsiang Lin,
MD; Eric Brader,
MD; Kent Berkey,
MD; Jennifer Ludovici,
Roland Kaufmann,
MD; Sharon De Cesare; Alan Hodgdon,
Malcolm Macleod,
M. Thompson,
Mariusz Piatkowski,
Robert V. O’Toole,
MD; Laurel Yasko,
RN; Kaveh Ilkhanipour,
MD; Rich Maenza,
Melissa Mathias,
CRNP; Keith Thulborn,
MD; Charles Jungreis,
MD; Pamela Cockley,
RN; Guy Corsello,
MD; Cheryl Ammon,
R Rasheed,
Paul A. Weston,
Mark S. Silverberg,
M. Harper,
Malcolm Robinson,
Mark MacEachern,
Petal Petersen Williams,
Martin Roth,
Brett L. Rice,
M Hogan,
Maria Antonietta Pellegrino,
M Holland,
Marianna LaNoue,
Marion D. Redding,
Michael H. Handler
Publication year - 2000
Publication title -
stroke
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.397
H-Index - 319
eISSN - 1524-4628
pISSN - 0039-2499
DOI - 10.1161/01.str.31.2.358
Subject(s) - medicine , placebo , stroke (engine) , adverse effect , clinical trial , randomized controlled trial , intracerebral hemorrhage , anesthesia , dosing , antagonist , subarachnoid hemorrhage , pathology , mechanical engineering , alternative medicine , receptor , engineering
Background and Purpose —GV150526 , a selective glycine site antagonist, reduces infarct volume in rats with focal cerebral ischemia. Safety and efficacy in humans with acute stroke are being investigated. We sought to further explore the safety, pharmacokinetics, and preliminary outcome ofGV150526 treatment in patients with a clinical diagnosis of acute stroke.Methods —Two trials were conducted in North America. The North American Glycine Antagonist in Neuroprotection trial (GAIN 1) (GLYA2001; United States only) was designed as a sequential dose escalation study. GAIN 2 (GLYA2005; United States and Canada) was designed to further assess the safety of the highest dose tolerated in GAIN 1. Both trials were randomized (2:1), double-blind, and placebo controlled. Treatment was started within 12 hours of symptom onset; patients with both ischemic stroke and primary intracerebral hemorrhage were included in both trials.Results —The dose escalation study (GAIN 1) completed 3 dosing tiers. Enrollment was suspended before escalation to the fourth tier because of laboratory reports of transiently elevated bilirubin levels in a concurrent European study that employed the dose targeted for this tier. After review by an independent safety committee of the worldwide safety data, the second study (GAIN 2) commenced. One hundred nine patients were randomized and dosed with study drug, either an 800-mg loading dose followed by 200 mg every 12 hours for 3 days ofGV150526 or placebo. The incidence of serious adverse events was similar in the drug and placebo groups. Mild irritation at the infusion site and symptoms suggestive of mild and reversible altered mentation were reported more frequently in theGV150526 group than in the placebo group. Hyperbilirubinemia was reported in 6% ofGV150526 -treated patients compared with 3% of placebo-treated patients. Outcome at 4 weeks after stroke was better inGV150526 -treated patients, but the studies were not powered to show statistical significance, and the baseline neurological deficits in theGV150526 -treated patients were less severe.Conclusions —These preliminary studies suggest thatGV150526 is well tolerated by patients with suspected acute stroke. Further pivotal studies testing the efficacy and safety ofGV150526 in acute stroke are ongoing.
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