Efficacy and Safety of Ryanodex� (EGL-4104) as Adjuvant Treatment in Subjects With Exertional Heat Stroke (EHS)

Condition(s) targeted: Heat Stroke

Intervention: Dantrolene sodium for injectable suspension (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Eagle Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Adrian Hepner, MD, Study Director, Affiliation: Eagle Pharmaceuticals, Inc.

Overall contact:
Adrian Hepner, MD, Phone: 201-326-5306, Email: ahepner@eagleus.com

Study EGL-4104-C-1502 is a phase 2, single-site, open-label, randomized, 2-arm parallel study of Ryanodex for the adjuvant treatment of exertional heat stroke (EHS) administered intravenously (IV), to current standard of care (SOC). SOC for the treatment of EHS is defined as effective body cooling, which should be implemented as quickly as available after diagnosis of exertional heat stroke.

Official title: Phase 2, Single-Site, Open-Label, Randomized, 2-Arm Parallel Study to Assess the Efficacy and Safety of Ryanodex® (EGL-4104) as Adjuvant Treatment in Subjects With Exertional Heat Stroke (EHS)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Cumulative incidence of recovery of level of consciousness defined as a Glasgow Coma Scale (GCS) GCS ≥ 13

Secondary outcome: Cumulative incidence of recovery of level of consciousness defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 over the course of the study

Detailed description: The study will take place at emergency medical facilities. Due to the life-threatening nature of exertional heat stroke (EHS), rapid assessment for inclusion into the study and subsequent immediate treatment must occur. Following initial triage and primary assessment of a subject, the subject's baseline status should be documented, and once a diagnosis of EHS is obtained, SOC treatment will be initiated immediately, the subject will be randomized to one of two treatment arms (SOC only or SOC plus Ryanodex). Patients will be remain hospitalized for up to 72 hours after administration of the first dose of study drug and implemented SOC and will receive all necessary supportive measures until resolution of symptoms. Study duration: 72 hours

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subjects may be entered in the study if they have a core body temperature obtained

rectally of ≥ 40. 0°C (104°F)

- Recent history or suspected recent history (prior 24 hours) of performing intense

physical activity (exertional activity)

- The subject has an impaired consciousness level as evidenced by a GCS score < 13

- The subject has tachycardia (heart rate ≥ 100 bpm)

Exclusion Criteria:

- The subject is diagnosed with or is suspected of having an acute clinically severe

infection, which in the opinion of the Investigator may increase the subject's risk for participating in the study and/or may impair the ability of performing and/or interpreting study assessments

- The subject has severe hyperthermia secondary to a condition other than heat stroke

(e. g., serotonin syndrome, thyrotoxicosis, pheochromocytoma, or brain hemorrhage)

- There is likelihood of head trauma in the past 6 months, or other significant

cardiovascular, pulmonary, hepatic, endocrine, or renal illness that in the opinion of the Investigator may increase the subject's risk for participating in the study and/or may impair the ability of performing and/or interpreting study assessments

- A female subject has a positive pregnancy test (urine) or evidence of active

lactation

- Reported known use of potent CYP3A4 inhibitors

- A known history of allergy or hypersensitivity to dantrolene

- A history of chronic and ongoing assisted mechanical ventilation prior to the onset

of EHS via an established artificial or supported airway (e. g., for severe chronic obstructive pulmonary disease [COPD], upper airway disease, impaired respiratory function). Note: Endotracheal intubation and mechanical ventilation as part of supportive measures for the treatment of EHS are allowed

Adrian Hepner, MD, Phone: 201-326-5306, Email: ahepner@eagleus.com

King Abdullah Medical City, Mecca, Saudi Arabia; Not yet recruiting

Starting date: September 2015
Last updated: August 13, 2015