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

Primary Purpose

Heat Stroke

Status

Completed

Phase

Phase 2

Locations

Saudi Arabia

Study Type

Interventional

Intervention

Dantrolene sodium for injectable suspension

About this trial

This is an interventional treatment trial for Heat Stroke

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Ryanodex

Standard of Care only (SOC)

Arm Description

Ryanodex (dantrolene sodium) for injectable suspension administered as an IV bolus, in addition to standard of care (SOC) treatment.

Standard of Care (SOC) treatment only, consisting of body cooling and supportive measures implemented immediately.

Outcomes

Primary Outcome Measures

Number of Subjects Achieving Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13

Number of subjects achieving a Glasgow Coma Scale(GCS) ≥ 13 at or prior to 90 minutes post-randomization. The Glasgow Coma Scale (GCS) is a reliable and objective way of recording the initial and subsequent level of consciousness in a person after a brain injury. The range of total GCS score is 3 to15 where a higher GCS score represents a better outcome. The scores of subscales are summed to determine the total score*. A GCS score of 13-15 is considered Mild impairment of consciousness; a GCS score of 9-12 is considered Moderate impairment of consciousness; and a GCS score of 3-8 is considered Severe. *Subscales: Eyes Response -Spontaneous=4; To sound =3; To Pressure=2; None=1; not tested. Verbal Response- Oriented=5; Confused=4; Words=3; Sounds=2; None-1; Not tested. Motor Response: Obeys Commands=6; Localizes=5; Normal Flexion=4; Abnormal Flexion=3; Extension=2; None=1; Not tested.

Secondary Outcome Measures

Full Information

NCT ID

NCT02513095

First Posted

July 21, 2015

Last Updated

June 8, 2021

Sponsor

Eagle Pharmaceuticals, Inc.

Collaborators

Quintiles, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02513095

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Completed

Study Start Date

September 2015 (undefined)

Primary Completion Date

September 2015 (Actual)

Study Completion Date

October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eagle Pharmaceuticals, Inc.

Collaborators

Quintiles, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heat Stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ryanodex

Arm Type

Experimental

Arm Description

Ryanodex (dantrolene sodium) for injectable suspension administered as an IV bolus, in addition to standard of care (SOC) treatment.

Arm Title

Standard of Care only (SOC)

Arm Type

No Intervention

Arm Description

Standard of Care (SOC) treatment only, consisting of body cooling and supportive measures implemented immediately.

Intervention Type

Drug

Intervention Name(s)

Dantrolene sodium for injectable suspension

Other Intervention Name(s)

Ryanodex; EGL-4104

Intervention Description

Ryanodex will be administered as a rapid IV push as a single doses of 2 mg/kg or as 1 mg/kg.

Primary Outcome Measure Information:

Title

Number of Subjects Achieving Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13

Description

Time Frame

90 minutes post-randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Adrian Hepner, MD

Organizational Affiliation

Eagle Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

City

Mecca

Country

Saudi Arabia

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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