NCT01893190

Brief 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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
73

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2013

Typical duration for phase_1

Geographic Reach
4 countries

23 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 2, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

July 8, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2013

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

February 5, 2018

Status Verified

January 1, 2018

Enrollment Period

2.3 years

First QC Date

July 2, 2013

Last Update Submit

January 31, 2018

Conditions

Ruptured Cerebral AneurysmRuptured Berry Aneurysm

Keywords

Ruptured saccular aneurysmnimodipinesafetytolerabilitySubarachnoid hemorrhage

Outcome Measures

Primary Outcomes (1)

  • Dose Escalation Period

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

    3 Months

Secondary Outcomes (1)

  • PK measurements

    3 Months

Study Arms (2)

Nimodipine

ACTIVE COMPARATOR

Nimodipine 60mg q4h for 21 days - oral

Drug: Nimodipine

Nimodipine Microparticles

EXPERIMENTAL

Single intraventricular injection

Drug: Nimodipine Microparticles

Interventions

NimodipineDRUG

Based upon Investigator Judgement

Also known as: Nimodipine Softgel, Nimodipine Tablet
Nimodipine
Nimodipine MicroparticlesDRUG

Based upon Investigator Judgement

Also known as: EG-1962
Nimodipine Microparticles

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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%;
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (23)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095-7436, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Maryland Medical Cnter

Baltimore, Maryland, 21201, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Overlook Medical Center

Summit, New Jersey, 07901, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Lenox Hill Hospital

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Mayfield Clinic Inc

Cincinnati, Ohio, 45219, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Calgary, Foothills Medical Centre

Calgary, Alberta, T2N 1N4, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University Health Network - Toronto General Division, Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

University of Saskatchewan, Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Charles University, Department of Neurosurgery

Prague, 16902, Czechia

Location

Helsinki University Central Hospital

Helsinki, 00260, Finland

Location

Related Publications (3)

  • 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.

    PMID: 31812149DERIVED

  • 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.

    PMID: 27932607DERIVED

  • 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.

    PMID: 25678453DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

NimodipineEG-1962

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DihydropyridinesPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNicotinic Acids

Study Officials

  • Daniel Hanggi

    HHU

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 2, 2013

First Posted

July 8, 2013

Study Start

September 1, 2013

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

February 5, 2018

Record last verified: 2018-01

Locations

FI(1)CZ(1)CA(5)US(16)