Subarachnoid Hemorrhage and Soluble Epoxide Hydrolase Inhibition Trial

NCT03318783 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 17614
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Soluble epoxide hydrolase (sEH) is the metabolizing enzyme of epoxyeicosatrienoic acids (EETs), which may play a role in reducing neuroinflammation and regulating cerebral blood flow after subarachnoid hemorrhage (SAH). Hypotheses: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability in the blood and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and efficacy of GSK2256294, a novel soluble epoxide hydrolase inhibitor in patients with aneurysmal SAH.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Delayed Cerebral Ischemia; Vasospasm, Cerebral; Endothelial Dysfunction

Keywords

Eicosanoids; Epoxyeicosatrienoic Acids

Outcome Measures

Primary Outcomes (1)

• Participants With Adverse Events

  Summary tables and listings will be provided for all reported adverse events, defined as adverse events that start on or after the first administration of study drug. The reported adverse event term will be assigned a standardized preferred term. Adverse events will be summarized based on the number and percentage of patients experiencing the event. In the event a patient experiences repeat episodes of the same adverse event, then the event with the highest severity grade and strongest causal relationship to study treatment will be used for purposes of incidence tabulations. All deaths will be reported in a patient listing, which will include the primary cause of death and the number of days between the date of the last dose of study drug and death.

  90 days

Secondary Outcomes (4)

• Study Day 7 and Study Day 10 Serum and CSF EET/ Dihyroxyeicosatrienoic (DHET) Ratio, by Mass Spectroscopic Analysis (ng/mL)

  10 days

• Study Day 7 and Study Day 10 Serum Epoxyoctadecenoic Acid (EPOME) to Dihydroxyoctadec-12-enoic Acid (DPOME) Ratio, by Mass Spectroscopic Analysis (ng/mL)

  10 days

• Serum Biomarkers of Endothelial Injury From Blood Samples Obtained on Study Day 7 and Study Day 10

  10 days

• CSF Biomarkers of Neuroinflammation, From Blood Samples Obtained on Study Day 7 and Study Day 10

  10 days

Other Outcomes (5)

• Hospital Length of Stay in Days

  90 days

• Discharge Disposition

  90 days

• Number of Participants With New Stroke on Hospital Discharge Imaging

  90 days

Study Arms (2)

GSK2256294

ACTIVE COMPARATOR

10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days.

Drug: GSK2256294

Placebo

PLACEBO COMPARATOR

10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days.

Drug: Placebo

Interventions

GSK2256294 DRUG

GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days.

GSK2256294

Placebo DRUG

Placebo will be administered in a single dose once daily enteral for a duration of 10 days.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18
• Head CT evidence of subarachnoid hemorrhage
• Digital subtraction cerebral angiography or CT angiogram documenting the presence of a cerebral aneurysm.

You may not qualify if:

• Symptom onset compatible with SAH of \> 3 days prior to admission to OHSU
• Absence of an indwelling external ventricular drain
• Administration of any of the following inducers/inhibitors of CYP3A4: ritonavir, indinavir, nelfinavir, saquinavir, clarithromycin, telithromycin, chloramphenicol, ketoconazole, itraconazole, nefazodone, cobicistat or enzalutamide.
• Suspected or confirmed pregnancy
• Preexisting severe neurologic deficit or condition
• Chronic renal failure requiring dialysis
• Severe terminal disease with life expectancy \<6 months
• Unable to read or understand written or spoken English or Spanish
• Refusal of informed consent

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Foundation for Anesthesia Education and Research: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Martini RP, Siler D, Cetas J, Alkayed NJ, Allen E, Treggiari MM. A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2022 Jun;36(3):905-915. doi: 10.1007/s12028-021-01398-8. Epub 2021 Dec 6.

  PMID: 34873674 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Interventions

N-((4-cyano-2-(trifluoromethyl)phenyl)methyl)-3-((4-methyl-6-(methylamino)-1,3,5-triazin-2-yl)amino)cyclohexanecarboxamide

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Ross Martini
• Organization: Oregon Health and Science University

martinir@ohsu.edu

4013386803

Study Officials

• Ross Martini, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigational pharmacy staff will maintain the randomization list and study/drug placebo assignment. Participants, care providers, the investigators and outcomes assessors will be blinded to the grouping.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Subjects will be randomized to one of the two treatment arms based on an unrestricted or "fair-coin" randomization procedure.

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 24, 2017
• Study Start: May 2, 2018
• Primary Completion: April 3, 2019
• Study Completion: January 9, 2020
• Last Updated: January 22, 2021
• Results First Posted: January 22, 2021

Record last verified: 2020-12

Locations

US (1)