Estudio fundamental aleatorizado, con doble ciego, controlado con placebo, con grupos paralelos, multicéntrico, en Fase III, para evaluar la seguridad y la eficacia de 1mg/kg/día de DP-b99 administrado por vía intravenosa durante cuatro días consecutivos frente a placebo, cuando se inicia en el plazo de nueve horas desde el inicio del ictus isquémicoA double blind, randomized, placebo-controlled, parallel group, multicenter Phase 3 pivotal study to assess the safety and efficacy of 1mg/kg/day intravenous DP-b99 over 4 consecutive days versus placebo when initiated within nine hours of acute ischemic stroke onset - MACSI

• Conditions: Ictus isquémico agudo /Acute Ischemic Stroke; MedDRA version: 12.0Level: LLTClassification code 10055221Term: Ischemic stroke

• Registration Number: EUCTR2009-012025-11-ES
• Lead Sponsor: D-Pharm Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-08
• Last Update Posted: 28 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 770

Inclusion Criteria

1. Male or females 18 to 85 years of age, inclusive

2. Have suffered an acute hemispheric ischemic stroke, defined as acute, focal, neurological deficit(s), secondary to a presumed vascular event, which must include at least one of the following components (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 3, 9 or 11):
- Visual
- Best Language
- Extinction and Inattention (formerly Neglect)

3. Have suffered the onset of an acute ischemic stroke that can be evaluated and treatment initiated within 9 hours after the onset of acute ischemic stroke symptoms. (Onset is defined as the time that the subject was last seen in a normal state, or bedtime for unwitnessed strokes occurring during sleep.)

4. Have at screening a NIHSS score of 10 to 16, inclusive

5. Have readily accessible peripheral venous access for clinical trial material (CTM) administration and blood sampling

6. Have the ability to understand the requirements of the study and be willing to provide written informed consent (IC) (as evidenced by signature on an informed consent document approved by an independent ethics committee (IEC), and agree to abide by the study restrictions and return for the required assessments. (In the event of incapacitated subjects, informed consent will be sought from a legally acceptable representative or by any other means as approved by the IRB or IEC).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Have an intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography (CT) scan or susceptibility-weighted magnetic resonance imaging (MRI)

2. Be a candidate for thrombolytic therapy or have been treated with thrombolytic therapy for the current stroke

3. Be delirious, comatose or stuporous (a score of ?2 on item 1.a of the NIHSS) 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. Have 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 (e.g., metabolic encephalopathies, hemiplegic migraine, multiple sclerosis, central nervous system tumor, convulsive disorder, monocular blindness)

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

7. Have suffered a myocardial infarction in the last 90 days

8. Have 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. Have rapid spontaneous improvement of neurological signs during screening/baseline assessments

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

11. Have 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. Have either severe hypertension (systolic blood pressure (BP) >220 mm Hg or diastolic BP >120 mm Hg) or hypotension (systolic BP <90 mm Hg), as measured by at least 2 consecutive supine measurements taken 10 minutes apart immediately prior to first drug administration

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

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

15. Be a female of childbearing potential (less than 2 years? postmenopausal or not surgically sterilized) 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 (IUD) and/or condom with spermicide (IUD, diaphragm, condoms alone or the rhythm method are not considered reliable methods)

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

17. Be currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines (amphetamine-like), cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics

18. Have received an investigational drug or product or participated in an investigational drug study within a period of 30 days prior to receiving study medi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to compare the clinical therapeutic effects of intravenous DP-b99 at a dose of 1.0 mg/kg initiated within nine hours of stroke onset and administered daily over 2 hours for 4 consecutive days versus placebo in subjects with moderately severe, acute ischemic stroke with clinical evidence of cortical involvement. The clinical outcome will be measured by the modified Rankin Scale at day 90.;Secondary Objective: The secondary objectives of this study are to compare the safety and tolerability, as well as post-stroke recovery at Day 90, in subjects treated with DP-b99 versus placebo.;Primary end point(s): The primary efficacy endpoint is the mRS score at 90 days (or on last rating) following stroke onset as analyzed across the whole distribution of scores (?shift analysis?).