Efficacy and Safety Study of DP-b99 in Treating Acute Ischemic Stroke

Phase 3

Terminated

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: DP-b99; Drug: Placebo

• Registration Number: NCT00893867
• Lead Sponsor: D-Pharm Ltd.

Brief Summary

The purpose of this trial is to determine if intravenous administration of the metal ion trapping agent DP-b99 up to 9 hours following acute ischemic stroke onset, and then for 3 additional days (4 consecutive days in total) is effective in improving long term outcome. Patients will be followed up for 3 months after the stroke.

Detailed Description

This will be a randomized, double-blind, placebo-controlled, multicenter, multi-national, parallel-arm, pivotal study comparing a placebo group to a DP-b99 group treated with intravenous 1.0 mg/kg/d for 4 consecutive days, in acute ischemic stroke patients with an entry National Institutes of Health Stroke Scale (NIHSS) score of 10-16 and a clinical syndrome that includes at least 1 of the following: language dysfunction, visual field defect or Extinction and Inattention (formerly Neglect) (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 9, 3 or 11). An interim analysis for futility will be performed after Day 90 (or last available observation) primary endpoint data have been collected on about 45% of subjects planned to be enrolled. Clinical trial material (CTM) will be administered within 9 hours after the onset of acute ischemic stroke symptoms. Subjects will be randomized at a ratio of 1:1 to receive either DP-b99 or placebo. A data and safety monitoring board (DSMB) will assess the accumulating safety data periodically and will oversee the interim futility analysis.

Study Timeline

• Study First Submitted: 2009-05-04
• Study First Submitted QC: 2009-05-05
• Study First Posted: 2009-05-06
• Study Start: 2009-12
• Primary Completion: 2012-04
• Study Completion: 2012-04
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-23
• Last Update Posted: 2012-10-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 446

Inclusion Criteria

Not provided

Exclusion Criteria

1. An intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography scan or susceptibility-weighted magnetic resonance imaging

2. A candidate for either:

   1. thrombolytic therapy, or have been treated with thrombolytic therapy for the current stroke
   2. mechanical thromboembolectomy, or have been treated with mechanical thromboembolectomy for the current stroke

3. Delirious, comatose or stuporous or demented, or having a mental impairment that in the investigator's opinion renders the subject incapable to participate in the study

4. Have seizure(s) anytime from stroke onset to screening/baseline NIHSS evaluation

5. Neurological or non-neurological comorbidities that in the investigator's opinion may lead, independent of the current stroke, to further deterioration in the subject's neurological status during the trial period, or may render the study's neurological assessments inconclusive for the purpose of evaluating solely the stroke's effects

6. Likely to undergo a procedure involving cardiopulmonary bypass during the study period

7. Suffered a myocardial infarction in the last 90 days

8. Any medical condition that in the investigator's opinion may threaten the subject's ability to complete the study (e.g., concurrent significant or life-threatening diseases, such as malignancies or end stage organ failure)

9. Rapid spontaneous improvement of neurological signs during screening/baseline assessments

10. Premorbid neurological deficits and functional limitations assessed by a pre-stroke Modified Rankin Scale score of > 1

11. Suffered a stroke within 90 days of the screening/baseline assessments that is either diagnostically confirmed or assumed to be in the same cerebral territory as is the current acute stroke

12. Either severe hypertension or hypotension, as measured by at least 2 consecutive supine measurements taken 10 minutes apart prior to randomization.

13. Significant current renal or hepatic disease(s): a serum creatinine concentration of >2.5 mg/dL; alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transferase values that are three times greater than the upper limit of normal.

14. Have a platelet count of <100,000/mm3 or, for patients on oral anticoagulants at study entry, INR of >4

15. Female of childbearing potential who is not willing to use adequate and effective birth control measures for the duration of the trial. Effective birth control measures include hormonal contraception, a barrier method such as a diaphragm, intrauterine device and/or condom with spermicide

16. Positive urine pregnancy test at screening/baseline or be a lactating female

17. Currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines, cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics

18. Received an investigational drug or product or participated in an investigational drug study within a period of 30 days prior to receiving study medication or have previously participated in a clinical trial involving DP-b99

19. Severe anemia as measured by a hemoglobin value of < 7 g/dl.

20. In a dependent relationship with the physician or the study sponsor.

21. Known hypersensitivity to any component of the investigational product.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DP-b99	DP-b99	-
Mannitol	Placebo	-

Primary Outcome Measures

Name	Time	Method
Modified Rankin Scale (mRS) categorical analysis ("shift")	90 days

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability	throughout study - baseline until day 90	the numbers of patients with treatment-emergent adverse events, results of physical examination, 12-lead electrocardiogram, vital signs and laboratory tests (complete blood count, chemistry and urinalysis)
Recovery, defined as a score of ≤ 1 on modified Rankin Score	90 days
recovery as assessed by an NIHSS of not more than 1	90 days
'home time'	90 days	exploratory endpoint of 'home time', which measures the length of time (as number of nights)spent at home/relatives' home between hospital discharge and day 90

Trial Locations

Locations (153)

CHU Jean Minjoz Besançon; 🇫🇷 Besancon, France

Triervlei Trial Centre; 🇿🇦 Western Cape, South Africa

Hospital Ramon y Cajal; 🇪🇸 Madrid, Spain

University Hospital Brno; 🇨🇿 Brno, Czech Republic

University Hospital Motol Clinic of Neurology; 🇨🇿 Prague, Czech Republic

University of Alberta Hospital; 🇨🇦 Edmonton, Canada

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Santa Casa de Misericordia de Belo Horizonte Departamento de Neurologia; 🇧🇷 Belo Horizonte, Brazil

Hospital Mãe de Deus; 🇧🇷 Porto Alegre, Brazil

Abt. Neurologie und Psychiatrie; 🇦🇹 Linz, Austria

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto Unidade de Emergência Centro de Estudos; 🇧🇷 Ribeirão Preto, Brazil

DRK Kliniken Berlin, Klinik fuer Neurologie; 🇩🇪 Berlin, Germany

Vivantes Klinikum Neukölln, Klinik für Neurologie, Stroke Unit; 🇩🇪 Berlin, Germany

Hopital Pellegrin-Tripode; 🇫🇷 Bordeaux, France

Chinook Regional Hospital; 🇨🇦 Lethbridge, Canada

Capital Health Regional Medical Center Neuroscience Institute; 🇺🇸 Trenton, New Jersey, United States

CHA- Hôpital de l'Enfant-Jésus; 🇨🇦 Quebec, Canada

Grey Nun's Community Hospital; 🇨🇦 Edmonton, Canada

LKH St. Pölten Department of Neurology; 🇦🇹 St. Pölten, Austria

Hospital Jihlava Clinic of Neurology; 🇨🇿 Jihlava, Czech Republic

County Hospital Pardubice Clinic of Neurology; 🇨🇿 Pardubice, Czech Republic

Presbitarian Hospital; 🇺🇸 Charlotte, North Carolina, United States

Ärztlicher Direktor Neurologische Klinik, Neurologische Klink GmbH der Rhoen-Klinikum AG; 🇩🇪 Bad Neustadt / Saale, Germany

Állami Egészségügyi Központ; 🇭🇺 Budapest, Hungary

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

Kenezy Korhaz Rendelointezet Egezsegugyi Szolgaltato Nonprofit Kft.; 🇭🇺 Debrecen, Hungary

University of Debrecen, Medical and Health Science Center; 🇭🇺 Debrecen, Hungary

Hopital Gui de Chauliac; 🇫🇷 Montpellier, France

Marien-Krankenhaus gGmbH, Abteilung für Neurologie; 🇩🇪 Bergisch Gladbach, Germany

Seoul National University Bundang Hospital; 🇰🇷 Seongnam, Korea, Republic of

Azienda Ospedaliera Sant'Andrea, Stroke Unit; 🇮🇹 Rome, Italy

Istituto Patologia Generale U.C.S.C; 🇮🇹 Rome, Italy

PM Flór Ferenc County Hospital; 🇭🇺 Kistarcsa, Hungary

Pécsi Tudományegyetem Klinikai Központ; 🇭🇺 Pecs, Hungary

ASKLEPIOS Fachklinikum Teupitz; 🇩🇪 Teupitz, Germany

Askepios Klinik Altona; 🇩🇪 Hamburg, Germany

Szpital Wolski im. dr Anny Gostyńskiej Samodzielny Publiczny Zakład Opieki Zdrowotnej, Oddział Neurologii; 🇵🇱 Warsaw, Poland

Centro de Estudos Egas Moniz - Hospital de Santa Maria; 🇵🇹 Lisboa, Portugal

Catharina Ziekenhuis Neurologie; 🇳🇱 Eindhoven, Netherlands

Dipartimento di Neuroscienze, Ospedale di Brotzu; 🇮🇹 Cagliari, Italy

Istituto Neurologico C. Mondino; 🇮🇹 Pavia, Italy

Chaim Sheba Medical Center; 🇮🇱 Tel Hashomer, Israel

Askepios Klinik Heidberg; 🇩🇪 Hamburg, Germany

Inha University Hospital; 🇰🇷 Incheon, Korea, Republic of

Aladár Petz County Teaching Hospital; 🇭🇺 Gyor, Hungary

Borsod-Abaúj-Zemplén County Hospital Miskolc; 🇭🇺 Miskolc, Hungary

Università di Perugia, Division of Internal and Cardiovascular Medicine - Stroke Unit; 🇮🇹 Perugia, Italy

ASAN Medical Center; 🇰🇷 Seoul, Korea, Republic of

Evangelische Kliniken Gelsenkirchen GmbH Klinik für Neurologie und Klinische Neurophysiologie; 🇩🇪 Gelsenkirchen, Germany

Wojewodzki Szpital Specjalistyczny Nr 1 im. Prof. Jozefa Gasinskiego; 🇵🇱 Tychy, Poland

Atrium MC Parkstad; 🇳🇱 Heerlen, Netherlands

Isala Klinieken Ploikliniek Neurologie; 🇳🇱 Zwolle, Netherlands

Ospedale di Circolo di Varese; 🇮🇹 Lombardia, Italy

Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

The Catholic University of Korea Seoul St. Mary's hospital; 🇰🇷 Seoul, Korea, Republic of

Università di Roma "La Sapienza" - Stroke Unit; 🇮🇹 Rome, Italy

Dong-A Medical Center; 🇰🇷 Busan, Korea, Republic of

Clinical Projects Research; 🇿🇦 Worcester, South Africa

Pomerania Traumatology Center, Regional Specialist Hospital im. Nicolaus Copernicus; 🇵🇱 Gdansk, Poland

Medisch Spectrum Twente Hoofd Afdeling Vasculaire Neurologie; 🇳🇱 Enschede, Netherlands

Hospital Gregorio Maranon; 🇪🇸 Madrid, Spain

Chonnam National University Hospital; 🇰🇷 Gwangju, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Hospital Vall D'hebron; 🇪🇸 Barcelona, Spain

Hospital La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Universitätsspital Basel, Neurologie; 🇨🇭 Basel, Switzerland

Helderberg Research Institute; 🇿🇦 Western Cape, South Africa

Hospital Universitario de Albacete; 🇪🇸 Albacete, Spain

Hospital De La Santa Ta Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Germans Triasy Pujol; 🇪🇸 Barcelona, Spain

Hospital Universitario Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario de Santiago; 🇪🇸 Santiago de Compostela, Spain

Associated Neurologists, P.C.; 🇺🇸 Danbury, Connecticut, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

The Methodist Hospital; 🇺🇸 Houston, Texas, United States

Istituto Scientifico San Raffaele - Stroke Unit; 🇮🇹 Milano, Italy

U.O.C. Stroke Unit; 🇮🇹 Rome, Italy

Hôpital Bichat; 🇫🇷 Paris, France

Santa Casa de Misericórdia de Porto Alegre Policlinica Santa Clara Sala de Neurologia; 🇧🇷 Porto Alegre, Brazil

Helios Klinikum Erfurt GmbH; 🇩🇪 Erfurt, Germany

Universitätsklinikum Erlangen, Neurologische klinik; 🇩🇪 Erlangen, Germany

Georg-August-Universitat Gottingen Neurologische Klinik; 🇩🇪 Gottingen, Germany

Klinikum der Otto-von-Guericke-Universität Magdeburg, Neurologische Universitätsklinik; 🇩🇪 Magdeburg, Germany

Krankenhaus der Bramherzigen Brüder; 🇩🇪 Trier, Germany

Heinrich Braun Klinikum Zwickau; 🇩🇪 Zwickau, Germany

Hospital Professor Doutor Fernando Fonseca, EPE; 🇵🇹 Amadora, Portugal

Fichmed; 🇿🇦 Bloemfontein, South Africa

Carilion Clinic; 🇺🇸 Roanoke, Virginia, United States

Legacy Meridian Park Medical Center; 🇺🇸 Tualatin, Oregon, United States

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Moinhos de Vento; 🇧🇷 Porto Alegre, Brazil

Hamilton Health Sciences Centre; 🇨🇦 Hamilton, Canada

Universitätsklinikum Ulm, Abteilung für Neurologie im RKU; 🇩🇪 Ulm, Germany

Universitätsklinikum Essen, Klinik und Poliklinik für Neurologie; 🇩🇪 Essen, Germany

Research Center of Southern California; 🇺🇸 Oceanside, California, United States

The University of Kentucky The Methodist Hospital; 🇺🇸 Lexington, Kentucky, United States

Memorial Health University Medical Center; 🇺🇸 Savannah, Georgia, United States

St. Elizabeth's Medical Center; 🇺🇸 Youngstown, Ohio, United States

Landeskrankenhaus Klagenfurt; 🇦🇹 Klagenfurt, Austria

Hospital São José de Joinville; 🇧🇷 Santa Catarina, Brazil

UNIFESP; 🇧🇷 San Paulo, Brazil

Hospital Santa Marcelina; 🇧🇷 Sao Paulo, Brazil

Kingston General Hospital; 🇨🇦 Kingston, Canada

University Hospital Hradec Kralove, Clinic of Neurology; 🇨🇿 Hradec Kralove, Czech Republic

Hospital Vítkovice Clinic of Neurology; 🇨🇿 Ostrava, Czech Republic

Clinic of Neurology, Stroke Center, Charles University; 🇨🇿 Prague, Czech Republic

University Hospital Kralovske Vinohrady; 🇨🇿 Prague, Czech Republic

CHU Henri Mondor; 🇫🇷 Créteil, France

Hôpital Saint Jean; 🇫🇷 Perpignan, France

Hôpital Lariboisière - Service Neurologie; 🇫🇷 Paris, France

Klinikum Chemnitz GmbH Chefarzt Klinik für Neurologie; 🇩🇪 Chemnitz, Germany

Klinikum Bremen-Mitte; 🇩🇪 Bremen, Germany

Klinikum Bremerhaven-Reinkenheide gGmbH, Neurologische Klinik; 🇩🇪 Bremerhaven, Germany

Klinikum Fulda, Neurologische Klinik; 🇩🇪 Fulda, Germany

Neurologische Universitätsklinik Freiburg, Neurozentrum; 🇩🇪 Freiburg, Germany

Ernst Moritz Arndt University; 🇩🇪 Grifswald, Germany

Klinikum Köln Merheim, Department of Neurology; 🇩🇪 Koln, Germany

Johannes Gutenberg Universitat, Klinik und Poliklinik fur Neurologie; 🇩🇪 Mainz, Germany

Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Neurologie; 🇩🇪 Leipzig, Germany

Klinikum 1 Minden, Neurologische Klinik; 🇩🇪 Minden, Germany

Universität Rostock Chefarzt Abteilung Neurologie; 🇩🇪 Rostock, Germany

Fővárosi Önkormányzat Péterfy Sándor utcai Kórház- Rendelőintézet és Baleseti Központ; 🇭🇺 Budapest, Hungary

Zala Megyei Kórház; 🇭🇺 Zalaegerszeg, Hungary

Neurological Dept. Edith Wolfson Medical Center; 🇮🇱 Holon, Israel

Ospedale Regionale Valle d'Aosta; 🇮🇹 Aosta, Italy

Meir Medical Center; 🇮🇱 Kfar Saba, Israel

Presidio Ospedaliero di Piacenza; 🇮🇹 Piacenza, Italy

Azienda Ospedaliera Universitaria "Santa Maria della Misericordia" Stroke Unit; 🇮🇹 Udine, Italy

Inje University ILSAN Paik Hospital; 🇰🇷 Goyang, Korea, Republic of

Inje University BUSAN Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Medical University of Lublin, Department of Neurology, Stroke Unit; 🇵🇱 Lublin, Poland

Constantiaberg Medi-clinic; 🇿🇦 Cape Town, South Africa

Union Hospital; 🇿🇦 Gauteng, South Africa

Consorcio Hospital General Universitario Valencia; 🇪🇸 Valencia, Spain

Hospital Clinico Universitario De Valladolid; 🇪🇸 Valladolid, Spain

Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Sandomierzu; 🇵🇱 Sandomierz, Poland

Wojskowy Instytut Medyczny, Oddział Neurologii; 🇵🇱 Warsaw, Poland

Szpital Powiatowy im. Marii Curie - Skłodowskiej w Skarżysku-Kamiennej; 🇵🇱 Skarżysko-Kamienna, Poland

Centro Hospitalar de Coimbra EPE; 🇵🇹 Coimbra, Portugal

Neurology Clinic, Faculty Hospital in Martin; 🇸🇰 Martin, Slovakia

Hospital un Poliklinic; 🇸🇰 Spisska Nova Ves, Slovakia

Neurology dept.,Hospital Zilina; 🇸🇰 Zilina, Slovakia

Instytut Psychiatrii i Neurologii Oddział Neurologiczny z Pododdziałem Udarowym; 🇵🇱 Warsaw, Poland

Hospital de São Sebastião, EPE; 🇵🇹 Santa Maria da Feira, Portugal

University Hospital Nitra; 🇸🇰 Nitra, Slovakia

Faculty Hospital Trnava; 🇸🇰 Trnava, Slovakia

Medical University of Warsaw, Department of Neurology; 🇵🇱 Warsaw, Poland

Hospitais da Universidadde de Coimbra, EPE; 🇵🇹 Coimbra, Portugal

Universitätsspital Zürich, Klinik für Neurologie; 🇨🇭 Zurich, Switzerland

University of Louisville, Kentucky Neuroscience Research; 🇺🇸 Louisville, Kentucky, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

Medizinische Universität Innsbruck; 🇦🇹 Innsbruck, Austria