Abstract Details

Title Safety and Tolerability of GTX-104 (Nimodipine Injection for IV Infusion) Compared With Oral Nimodipine in Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective, Randomized Trial

Topic Neuro Trauma and Critical Care

Presentation(s) S21 - Neurocritical Care (1:00 PM-1:12 PM)

Poster/Presentation
Number 001

Objective To conduct a randomized, open label, blinded endpoint study of GTX-104 (intravenous [IV] nimodipine) compared with oral nimodipine in patients with aSAH.

Background Oral nimodipine is the only drug approved for aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is poor and peak plasma concentrations fluctuate widely, leading to dose-limiting hypotension. Administration is problematic in patients who cannot swallow. GTX-104 is an IV nimodipine formulation that has 100% bioavailability and is not affected by swallowing, gastrointestinal absorption and first pass effects. When administered in pharmacokinetically-equivalent doses to oral nimodipine in healthy humans, GTX-104 has more consistent plasma concentrations and causes less hypotension than oral nimodipine.

Design/Methods Multicenter, prospective, randomized, open-label safety and tolerability study of GTX-104 compared to oral nimodipine in aSAH. Inclusion/exclusion criteria matched prescribing information for oral nimodipine and included adults with aSAH of all Hunt/Hess grades. Subjects were randomized 1:1 to GTX-104 or oral nimodipine. The primary endpoint was the proportion of participants with clinically significant hypotension (hypotension requiring treatment, with a reasonable likelihood of being due to study drug, as determined by an independent, blinded committee). Secondary endpoints included all episodes of hypotension, adverse events, EQ-5D-3L and modified Rankin scale within 90 days of aSAH.

Results 102 participants were randomized at 24 sites in the USA. Demographics reflected those of aSAH. There was a 20% relative reduction in clinically significant hypotension with GTX-104 compared to oral nimodipine (28% versus 35%). 54% of GTX-104 subjects got >95% of the prescribed dose compared to 8% on oral nimodipine. Favorable outcome (90-day mRS 0-2) was 62% in the GTX-104 and 48% in the oral nimodipine group. Fewer patients on GTX-104 (36% versus 48% oral nimodipine) had serious adverse events.

Conclusions GTX-104, an IV formulation of nimodipine that can be administered through central or peripheral veins, is safer and potentially more efficacious than oral nimodipine.

Authors/Disclosures
Loch Macdonald, MD, PhD PRESENTER	Dr. Macdonald has received personal compensation for serving as an employee of Grace Therapeutics. Dr. Macdonald has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Grace Therapeutics. Dr. Macdonald has stock in Grace Therapeutics. The institution of Dr. Macdonald has received research support from Community Health Partners. Dr. Macdonald has received publishing royalties from a publication relating to health care. Dr. Macdonald has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with National Institutes of Health.
Huimahn A. Choi, MD (The University of Texas Health Science Center At Houston)	The institution of Dr. Choi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acasti Pharma.
Sherry Hsiang-Yi Chou, MD (Departmnt of Neurology, Northwestern Feinberg School of Medicine)	Dr. Hsiang-Yi Chou has received personal compensation for serving as an employee of NIH. An immediate family member of Dr. Hsiang-Yi Chou has received personal compensation for serving as an employee of Wells Fargo. Dr. Hsiang-Yi Chou has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Grace Therapeutics. The institution of Dr. Hsiang-Yi Chou has received research support from The Neurocritical Care Society. Dr. Hsiang-Yi Chou has a non-compensated relationship as a Board of Director member with United Council of Neurologic Specialties that is relevant to AAN interests or activities. Dr. Hsiang-Yi Chou has a non-compensated relationship as a Co-chair/chair-elect, the Neurocritical Care Committee with American Heart Association, the Stroke Council that is relevant to AAN interests or activities. Dr. Hsiang-Yi Chou has a non-compensated relationship as a Co-chair/chair ellect, the Neurocritical Care Special Interest Group with American Neurologic Association that is relevant to AAN interests or activities.
Andrew Ducruet, MD	Andrew Ducruet, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kos. Andrew Ducruet, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Andrew Ducruet, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Phenox. Andrew Ducruet, MD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Penumbra. Andrew Ducruet, MD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Grace Therapeutics. The institution of Andrew Ducruet, MD has received research support from National Institute of Health.
W. T. Kimberly, MD, PhD (Massachusetts General Hospital)	Dr. Kimberly has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astrocyte Pharmaceuticals. Dr. Kimberly has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acasti Pharma. Dr. Kimberly has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Kimberly has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Stryker. Dr. Kimberly has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurotherapeutics. Dr. Kimberly has stock in Woolsey Pharmaceuticals. Dr. Kimberly has stock in Acasti Pharma. The institution of Dr. Kimberly has received research support from NIH. The institution of Dr. Kimberly has received research support from Hyperfine, Inc.. The institution of Dr. Kimberly has received research support from Alzheimer's Association. Dr. Kimberly has received intellectual property interests from a discovery or technology relating to health care.
Alejandro A. Rabinstein, MD, FAAN (Mayo Clinic)	Dr. Rabinstein has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Shionogi . Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ceribell. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurocritical care/NCS-Springer. Dr. Rabinstein has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters/UptoDate. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for EBSCO/DynaMed. Dr. Rabinstein has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AHA. Dr. Rabinstein has received publishing royalties from a publication relating to health care. Dr. Rabinstein has received publishing royalties from a publication relating to health care. Dr. Rabinstein has received publishing royalties from a publication relating to health care. Dr. Rabinstein has received publishing royalties from a publication relating to health care.

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