Clinical trial NCT02893826: Safety/Pharmacokinetic Study Comparing Intracisternal EG-1962 to Standard of Care Enteral Nimodipine in Adults With aSAH
Official title: Multicenter, Controlled, Randomized, Safety and Pharmacokinetic Study Comparing Intracisternal EG-1962 to Standard of Care Enteral Nimodipine in Adults With Aneurysmal Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Keywords: Aneurysm
Ruptured
nimodipine
subarachnoid hemorrhage
Lead sponsor: Edge Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2016-09-09
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Safety and Pharmacokinetic study comparing intracisternal EG-1962 to enternal nimopidine in the treatment of aneurysmal subarachnoid hemorrhage.


Eligibility criteria: Inclusion Criteria:

1. Ruptured saccular aneurysm repaired by neurosurgical clipping
2. Subarachnoid hemorrhage on computed tomography (CT) scan of grade 2-4 on the modified Fischer scale
3. WFNS grade 1 or 2 assessed during the Pre-randomization Phase. If WFNS grade 2, must not require an EVD prior to aneurysm repair

Exclusion Criteria:

1. 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
2. Angiographic vasospasm prior to randomization
3. Evidence of cerebral infarction with neurological deficit

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: 90 Days
measure: Proportion of subjects with delayed cerebral infarctions present on CT at Day 30
timeFrame: 30 Days
Secondary outcomes:
measure: Pharmacokinetic (PK) profile of EG-1962 as measured by maximum drug concentration in plasma (Cmax)
timeFrame: At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and daily thereafter until hospital discharge or Day 21, whichever occurs first and Day 30
measure: Pharmacokinetic (PK) profile of EG-1962 as measured by time to reach maximum drug concentration in plasma (Tmax)
timeFrame: At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and daily thereafter until hospital discharge or Day 21, whichever occurs first and Day 30
measure: Pharmacokinetic (PK) profile of EG-1962 as measured by steady state concentration (Css)
timeFrame: At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and daily thereafter until hospital discharge or Day 21, whichever occurs first and Day 30
measure: Pharmacokinetic (PK) profile of EG-1962 as measured by AUC area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC024h)
timeFrame: At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours
measure: Pharmacokinetic (PK) profile of EG-1962 as measured by AUC from 0 to Day 10 (AUC0-10)
timeFrame: At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and up to Day 10
measure: Pharmacokinetic (PK) profile of EG-1962 as measured by AUC from 0 to Day 14 (AUC0-14)
timeFrame: At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and up to Day 14
measure: Pharmacokinetic (PK) profile of EG-1962 as measured by AUC from 0 to last plasma concentration (AUC0-last)
timeFrame: At the time of the first post-operation blood draw and every 6 hours (± 30 minutes) for the first 24 hours and up to last plasma concentration
Other outcomes:
measure: Extended Glasgow Outcome Scale (GOSE)
timeFrame: Day 90
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Day 90
Locations:
city: Phoenix
country: United States
facility: Dignity Health; St. Joseph's Hospital and Medical Center
state: Arizona
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Baltimore
country: United States
facility: University of Maryland Medical Systems
state: Maryland
city: Edmonton
country: Canada
facility: University of Alberta Hospital/Mackenzie Health Sciences Centre
state: Alberta
Study officials:
affiliation: Edge Therapeutics Inc
name: R. Loch Macdonald, MD, PhD
role: STUDY_CHAIR
References:
citation: Macdonald RL, Hanggi D, Ko NU, Darsaut TE, Carlson AP, Wong GK, Etminan N, Mayer SA, Aldrich EF, Diringer MN, Ng D, Strange P, Bleck T, Grubb R, Suarez JI. NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage. Neurosurgery. 2020 Dec 15;88(1):E13-E26. doi: 10.1093/neuros/nyaa430.