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Ruptured Cerebral AneurysmPhase 1/2NEWTONNCT01893190

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

A Phase 1/2 study testing Nimodipine and Nimodipine Microparticles in people with Ruptured Cerebral Aneurysm and Ruptured Berry Aneurysm, run by Edge Therapeutics Inc at 23 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Nimodipine and Nimodipine Microparticles
Could I receive a placebo?
No, everyone receives an active treatment
How many people
73 participants
Where
23 sitesin 4 countries
Study dates
Sep 2013to Jan 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

23 sites in 4 countries.

23 sites in 4 countries

United States16 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • University of Maryland Medical Cnter

    Baltimore, Maryland, 21201

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29425

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Mayfield Clinic Inc

    Cincinnati, Ohio, 45219

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90095-7436

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Columbia University

    New York, New York, 10032

  • Lenox Hill Hospital

    New York, New York, 10065

  • Barrow Neurological Institute

    Phoenix, Arizona, 85013

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Overlook Medical Center

    Summit, New Jersey, 07901

Other trials in United States

Canada5 sites

  • University of Calgary, Foothills Medical Centre

    Calgary, Alberta, T2N 1N4

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

  • University of Saskatchewan, Royal University Hospital

    Saskatoon, Saskatchewan, S7N 0W8

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • University Health Network - Toronto General Division, Toronto Western Hospital

    Toronto, Ontario, M5T 2S8

Other trials in Canada

Czechia1 site

  • Charles University, Department of Neurosurgery

    Prague, 16902

Other trials in Czechia

Finland1 site

  • Helsinki University Central Hospital

    Helsinki, 00260

Other trials in Finland

About this study

Official title: 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

Read the 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.

Being tested
Nimodipine, Nimodipine Microparticles
Keywords
Ruptured saccular aneurysm, nimodipine, safety, tolerability, Subarachnoid hemorrhage
Medical subject headings
Subarachnoid Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NimodipineDrug

    Also called Nimodipine Softgel, Nimodipine Tablet

    Based upon Investigator Judgement

  • Nimodipine MicroparticlesDrug

    Also called EG-1962

    Based upon Investigator Judgement

Study groups in NCT01893190
Study groupRoleWhat they receive
NimodipineActive comparatorNimodipine 60mg q4h for 21 days - oral
Receives: Drug: Nimodipine
Nimodipine MicroparticlesExperimentalSingle intraventricular injection
Receives: Drug: Nimodipine Microparticles

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Escalation Period

    To determine the maximum tolerated dose (MTD) of intraventricular EG 1962.

    Measured: 3 Months

Secondary outcomes (1)

  1. PK measurements

    To measure plasma and cerebrospinal fluid (CSF) concentrations of nimodipine

    Measured: 3 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2013 (estimated)
  2. Study startSep 2013
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01893190
Sponsor's protocol ID
EG-01-1962-02
Other IDs
2013-000954-23
Acronym
NEWTON
Status last verified
Jan 2018
First submitted
2 Jul 2013
Last updated
5 Feb 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Macdonald RL, Hanggi D, Strange P, Steiger HJ, Mocco J, Miller M, Mayer SA, Hoh BL, Faleck HJ, Etminan N, Diringer MN, Carlson AP, Aldrich F; NEWTON Investigators. Nimodipine pharmacokinetics after intraventricular injection of sustained-release nimodipine for subarachnoid hemorrhage. J Neurosurg. 2019 Dec 6;134(1):95-101. doi: 10.3171/2019.9.JNS191366. Print 2021 Jan 1.

    PubMed 31812149

  • Hanggi D, Etminan N, Aldrich F, Steiger HJ, Mayer SA, Diringer MN, Hoh BL, Mocco J, Faleck HJ, Macdonald RL; NEWTON Investigators. Randomized, Open-Label, Phase 1/2a Study to Determine the Maximum Tolerated Dose of Intraventricular Sustained Release Nimodipine for Subarachnoid Hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage]). Stroke. 2017 Jan;48(1):145-151. doi: 10.1161/STROKEAHA.116.014250. Epub 2016 Dec 8.

    PubMed 27932607

  • Hanggi D, Etminan N, Macdonald RL, Steiger HJ, Mayer SA, Aldrich F, Diringer MN, Hoh BL, Mocco J, Strange P, Faleck HJ, Miller M. NEWTON: Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage. Neurocrit Care. 2015 Oct;23(2):274-84. doi: 10.1007/s12028-015-0112-2.

    PubMed 25678453

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nimodipine and Nimodipine Microparticles in people with Ruptured Cerebral Aneurysm and Ruptured Berry Aneurysm, run by Edge Therapeutics Inc at 23 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Canada, Czechia, Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation Period (time frame: 3 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01893190, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018; AzTrials last refreshed its copy on 8 Nov 2026.

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