Efficacy and Safety of Ryanodex® (EGL-4104) as Adjuvant Treatment in Subjects With Exertional Heat Stroke (EHS)
Condition: Heat Stroke
MeSH terms: Stroke; Heat Stroke; Sunstroke
Intervention: Dantrolene sodium for injectable suspension
Intervention description: Ryanodex will be administered as a rapid IV push as a single doses of 2 mg/kg or as 1 mg/kg.
Intervention MeSH terms: Dantrolene
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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