Overview

This trial is active, not recruiting.

Conditions ischemic stroke, malignant edema
Treatment rp-1127 (glyburide for injection)
Phase phase 2
Sponsor Remedy Pharmaceuticals, Inc.
Start date May 2013
End date August 2015
Trial size 83 participants
Trial identifier NCT01794182, RPI 203

Summary

This is a randomized, multi-center, prospective, double blind study. The primary objective is to demonstrate the efficacy of RP-1127 compared to placebo in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. This objective will be addressed by comparing the proportion of RP-1127 treated patients and placebo treated patients with a Day 90 modified Rankin Scale (mRS) ≤ 4 without decompressive craniectomy (DC).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Placebo Comparator)
Subjects will receive matching placebo.
(Experimental)
Subjects will receive the active agent, RP-1127 (Glyburide for Injection)
rp-1127 (glyburide for injection) glibenclamide
Glyburide (5-chloro-N-(4-[N-(cyclohexylcarbamoyl) sulfamoyl]phenethyl)-2- methoxybenzamide) is an anti-diabetic medication in a class of medications known as sulfonylureas. RP-1127 is a formulation of glyburide designed for intravenous administration.

Primary Outcomes

Measure
The proportion of patients with a modified Rankin Scale (mRS) at Day 90 ≤ 4 without decompressive craniectomy
time frame: 90 Days
Safety of RP-1127 in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema.
time frame: 90 Days

Secondary Outcomes

Measure
Proportion of subjects undergoing DC or dead within 14 days
time frame: 14 days
The change between baseline and 72-96 hours in ipsilateral hemispheric swelling measured by MRI
time frame: 96 hours
The change between baseline and 72-96 hours in lesional swelling measured by MRI
time frame: 96 hours

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: - A clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA territory involvement in addition to primary MCA territory stroke is acceptable). - Prior to stroke, no disability, or no significant disability despite symptoms (able to carry out all usual duties and activities). - A baseline DWI lesion between 82 and 300 cm3 on MRI. - Patients treated with IV rtPA should meet established criteria for IV rtPA administration in the 0-3 and 3-4.5 hr time periods at the time of rtPA administration (if rtPA is administered in the 3-4.5 hr time window, the NIHSS must be ≤ 25 at the time of rtPA administration). - The time to the start of infusion of Study Drug must be ≤ 10 hours after time of symptom onset, if known, or the time last seen well [termed "time last known at neurologic baseline" (TLK@B)]. - Age ≥18 years and ≤80 years. - Provision of written informed consent by a legally authorized representative according to institutional guidelines and national regulations. Exclusion Criteria: - Commitment to decompressive craniectomy (DC) prior to enrollment, or following enrollment and prior to start of Study Drug. - Treatment with intra-arterial (IA) rtPA or by mechanical means for clot disruption. - Patients unable to tolerate MRI scanning, e.g. those with pacemakers or automatic defibrillators. - Evidence (clinical or imaging) of concurrent infarction in the contralateral hemisphere deemed by the investigator to be sufficiently serious so as to affect functional outcome. - Clinical signs of herniation, e.g. one or two dilated, fixed pupils; unconsciousness (i.e., ≥ 2 on item 1a on the NIHSS); and/or loss of other brain stem reflexes attributable to edema or herniation according to the investigator's judgment. - Hemorrhage (other than small petechial hemorrhages) on CT/MRI, or CT/MRI evidence of anteroseptal/pineal shift greater ≥2 mm prior to enrollment that is due to cerebral edema. - Severe renal disorder from the patient's history (e.g. dialysis) or eGFR of < 30 mL/min/1.73 m2. - Severe liver disease or ALT >3 times normal, or bilirubin >2 times normal. - Blood glucose <55 mg/dL at enrollment or immediately prior to administration of Study Drug, or a clinically significant history of hypoglycemia. - Acute ST elevation myocardial infarction, and/or acute decompensated HF, and/or QTc>520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an ACS, MI, or coronary intervention (PCI or coronary artery surgery) within the past 3 months. - Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide /glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); netaglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); glibornuride (Glutril). - Known allergy to sulfa or specific allergy to sulfonylurea drugs. - Known G6PD enzyme deficiency. - Pregnant women. Women must be either post-menopausal (as confirmed by the LAR), permanently sterilized or, if ≤ 50 years old must have a negative test for pregnancy obtained before enrollment. - Breast-feeding women who do not agree (or their LAR does not agree) to stop breast- feeding during Study Drug infusion and for 7 days following the end of Study Drug infusion. - Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <3 months not related to current stroke, or those unlikely to be compliant with follow up. - Patients currently receiving an investigational drug. - Patients in whom a peripheral IV line cannot be placed. - Mentally incompetent (prior to qualifying stroke) patients and wards of the state. - Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented).

Additional Information

Official title A Randomized, Multi-center, Prospective, Double Blind, Phase II Trial of RP- 1127 (Glyburide for Injection) in Patients With a Severe Anterior Circulation Ischemic Stroke Who Are Likely to Develop Malignant Edema
Principal investigator Kevin N Sheth, MD
Description The study population consists of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke, a baseline diffusion weighted image (DWI) lesion between 82 and 300 cm3, age 18-80 years, and time from symptom onset to start of study infusion of ≤10 hours. The study will enroll both patients that do not receive IV rtPA and those that receive IV rtPA within 4.5 hours of stroke. Enrollment will be randomized controlling for site, age ≤60 (yes/no), and IV rtPA treatment at baseline (yes/no). Subjects will be randomized equally between RP-1127 and placebo.
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by Remedy Pharmaceuticals, Inc..