Safety and Tolerability Study of EG-1962 in Aneurysmal Subarachnoid Hemorrhage (NEWTON)

January 31, 2018 updated by: Edge Therapeutics Inc

Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After subarachNoid Hemorrhage: Phase I/IIa Multicenter, Controlled, Randomized, Open Label, Dose Escalation, Safety, Tolerability, and Pharmacokinectic Study Comparing EG-1962 and Nimodipine in Patients With Aneurysmal Subarachnoid Hemorrhage

Phase 1/2a Multicenter, Controlled, Randomized, Open Label, Dose Escalation, Safety, Tolerability, and Pharmacokinetic Study Comparing EG-1962 and Nimodipine in Patients with Aneurysmal Subarachnoid Hemorrhage

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1/2a multicenter, controlled, open label, and randomized, study.

Part 1 of the study is a single dose escalation period to determine the MTD of EG-1962. During this period, a maximum of 6 dose level cohorts with up to 12 patients per cohort will be enrolled. In each cohort, patients will be randomly assigned in a ratio of 3:1 to receive either intraventricular EG 1962 or enteral nimodipine, respectively. The first cohort will receive 100 mg EG 1962. Upon completion of the dose escalation period, a safe and tolerable dose will be selected for further study.

Part 2 of the study is a treatment period to assess the safety and tolerability of the selected dose of EG-1962.

The safety and tolerability of a single intraventricular dose of EG 1962 will be compared to enteral nimodipine (60 mg given every 4 hours orally or via nasogastric or gastrostomy tube) for 21 days.

Study Type

Interventional

Enrollment (Actual)

73

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 1N4
        • University of Calgary, Foothills Medical Centre
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Hospital
    • Ontario
      • Toronto, Ontario, Canada, M5B 1W8
        • St. Michael's Hospital
      • Toronto, Ontario, Canada, M5T 2S8
        • University Health Network - Toronto General Division, Toronto Western Hospital
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • University of Saskatchewan, Royal University Hospital
  • Czechia
      • Prague, Czechia, 16902
        • Charles University, Department of Neurosurgery
  • Finland
      • Helsinki, Finland, 00260
        • Helsinki University Central Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute
    • California
      • Los Angeles, California, United States, 90095-7436
        • Ronald Reagan UCLA Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Cnter
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Summit, New Jersey, United States, 07901
        • Overlook Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico
    • New York
      • New York, New York, United States, 10032
        • Columbia University
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10065
        • Lenox Hill Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Mayfield Clinic Inc
      • Cleveland, Ohio, United States, 44195
        • The Cleveland Clinic Foundation
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina (MUSC)
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female between the ages of 18 to 75 years, inclusive;
  • WFNS Grade 2, 3, or 4 assessed after treatment of the aneurysm but prior to administration of EG-1962;
  • Ruptured saccular aneurysm confirmed by angiography (catheter or CTA) and treated by neurosurgical clipping or endovascular coiling;
  • Subarachnoid hemorrhage on baseline CT scan that is diffuse (clot present in both hemispheres) thick (>4 mm) or thin, or local thick;
  • External ventricular drain (EVD) in place;
  • The patient is able to receive EG-1962 within 60 hours of the onset of subarachnoid hemorrhage (SAH). Onset of SAH is defined as the time the patient experiences the first symptom of SAH (e.g., severe headache or loss of consciousness reported either by patient or by a witness). If found unconscious, the onset of SAH is defined as the last time the patient was seen at baseline neurological state;
  • Weight >45 kg;
  • Hemodynamically stable after resuscitation with systolic blood pressure (SBP) ≥90 mm Hg without the use of inotropic agents;
  • Signed informed consent from the patient or the patient's legal representative after the completion of aneurysm repair and after all study criteria are confirmed; and
  • Female patients of child bearing potential must have negative pregnancy test . Male patients must agree to use adequate birth control during the study and up to 1 month after the discontinuation of the study drug treatment.

Exclusion Criteria:

  • Subarachnoid hemorrhage due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or infective aneurysm);
  • WFNS Grade 1 or 5 assessed after completion of the aneurysm repair but prior to administration of EG-1962;
  • Increased intracranial pressure >30 mm Hg in sedated patients lasting >4 hours anytime since admission;
  • Intraventricular or intracerebral hemorrhage in absence of SAH or with only local, thin SAH;
  • Angiographic vasospasm prior to aneurysm repair procedure, as documented by catheter angiogram or CT angiogram;
  • Major complication during aneurysm repair such as, but not limited to, massive intraoperative hemorrhage, brain swelling, arterial occlusion, or inability to secure the ruptured aneurysm;
  • Aneurysm repair requiring flow diverting stent or stent-assisted coiling and dual antiplatelet therapy;
  • Hemodynamically unstable prior to administration of study drug (i.e., SBP <90 mm Hg, requiring >6 L colloid, or crystalloid fluid resuscitation;
  • Cardiopulmonary resuscitation was required following SAH;
  • Female patients with positive pregnancy test (blood or urine) at screening;
  • History within the past 6 months and/or physical finding on admission of decompensated heart failure (New York Heart Association Class III and IV or heart failure requiring hospitalization);
  • Acute myocardial infarction within 3 months prior to the administration of the study drug;
  • Symptoms or electrocardiogram (ECG)-based signs of acute myocardial infarction or unstable angina pectoris on admission;
  • Electrocardiogram evidence and/or physical findings compatible with second or third degree heart block or of cardiac arrhythmia associated with hemodynamic instability;
  • Echocardiogram, if performed as part of standard-of-care before treatment, revealing a left ventricular ejection fraction <40%;
  • Severe or unstable concomitant condition or disease (e.g., known significant neurologic deficit, cancer, hematologic, or coronary disease), or chronic condition (e.g., psychiatric disorder), that, in the opinion of the Investigator, may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results;
  • Patients who have received an investigational product or participated in another interventional clinical study within 30 days prior to randomization. Patients participating in a non-interventional study that has no bearing on assessment of EG-1962 or enteral nimodipine can be enrolled per guidelines of the local Institutional Review Board (IRB) / independent Ethics Committee (IEC).
  • Kidney disease as defined by plasma creatinine ≥2.5 mg/dl (221 μmol/l); liver disease as defined by total bilirubin >3 mg/dl (51.3 μmol/l); and/or known diagnosis or clinical suspicion of liver cirrhosis; or Known hypersensitivity to nimodipine or other dihydropyridine calcium channel antagonists, poly-D, L-lactide-co-glycolide (PLGA), or hyaluronic acid.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nimodipine
Nimodipine 60mg q4h for 21 days - oral
Drug: Nimodipine
Based upon Investigator Judgement
Other Names:
  • Nimodipine Softgel
  • Nimodipine Tablet
Experimental: Nimodipine Microparticles
Single intraventricular injection
Drug: Nimodipine Microparticles
Based upon Investigator Judgement
Other Names:
  • EG-1962

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation Period
Time Frame: 3 Months
To determine the maximum tolerated dose (MTD) of intraventricular EG 1962.
3 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PK measurements
Time Frame: 3 Months
To measure plasma and cerebrospinal fluid (CSF) concentrations of nimodipine
3 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Edge Therapeutics Inc

Investigators

  • Principal Investigator: Daniel Hanggi, HHU

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

July 2, 2013

First Submitted That Met QC Criteria

July 2, 2013

First Posted (Estimate)

July 8, 2013

Study Record Updates

Last Update Posted (Actual)

February 5, 2018

Last Update Submitted That Met QC Criteria

January 31, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EG-01-1962-02
  • 2013-000954-23 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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