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)

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

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

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

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

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

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

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

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

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

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

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