Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of Ryanodex as Adjuvant Treatment in Subjects With EHS (NCT NCT03600376)

Last Updated: 2021-05-19

Results Overview

The GCS is a validated and reliable scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

17 participants

Primary outcome timeframe

90 minutes post-randomization

Results posted on

2021-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Ryanodex and Standard of Care In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered. Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push	Standard of Care Only (SOC) Standard of Care treatment will consist of the immediate start of cooling measures. Standard of Care: Body cooling measures and supportive measures
Overall Study STARTED	9	8
Overall Study COMPLETED	7	2
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Ryanodex and Standard of Care In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered. Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push	Standard of Care Only (SOC) Standard of Care treatment will consist of the immediate start of cooling measures. Standard of Care: Body cooling measures and supportive measures
Overall Study Adverse Event	1	1
Overall Study Transferred to other facility	1	0
Overall Study Investigator Decision	0	4
Overall Study Determined to be ineligible for study	0	1

Baseline Characteristics

It was not possible to obtain accurate height measurements for several patients due to the extreme nature of their medical condition.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ryanodex and Standard of Care n=9 Participants In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered. Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push	Standard of Care Only (SOC) n=8 Participants Standard of Care treatment will consist of the immediate start of cooling measures. Standard of Care: Body cooling measures and supportive measures	Total n=17 Participants Total of all reporting groups
Age, Continuous	55.3 years STANDARD_DEVIATION 7.2 • n=9 Participants	53.4 years STANDARD_DEVIATION 11.2 • n=8 Participants	54.4 years STANDARD_DEVIATION 9.0 • n=17 Participants
Sex: Female, Male Female	7 Participants n=9 Participants	5 Participants n=8 Participants	12 Participants n=17 Participants
Sex: Female, Male Male	2 Participants n=9 Participants	3 Participants n=8 Participants	5 Participants n=17 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=9 Participants	0 Participants n=8 Participants	0 Participants n=17 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=9 Participants	0 Participants n=8 Participants	3 Participants n=17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=9 Participants	8 Participants n=8 Participants	14 Participants n=17 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	0 Participants n=8 Participants	0 Participants n=17 Participants
Race (NIH/OMB) Asian	6 Participants n=9 Participants	4 Participants n=8 Participants	10 Participants n=17 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=8 Participants	0 Participants n=17 Participants
Race (NIH/OMB) Black or African American	0 Participants n=9 Participants	0 Participants n=8 Participants	0 Participants n=17 Participants
Race (NIH/OMB) White	1 Participants n=9 Participants	0 Participants n=8 Participants	1 Participants n=17 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=8 Participants	0 Participants n=17 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=9 Participants	4 Participants n=8 Participants	6 Participants n=17 Participants
Region of Enrollment Saudi Arabia	9 participants n=9 Participants	8 participants n=8 Participants	17 participants n=17 Participants
Weight	86.1 kg STANDARD_DEVIATION 16.9 • n=9 Participants	84.2 kg STANDARD_DEVIATION 12.9 • n=8 Participants	85.2 kg STANDARD_DEVIATION 14.7 • n=17 Participants
Height	162.8 cm STANDARD_DEVIATION 7.6 • n=8 Participants • It was not possible to obtain accurate height measurements for several patients due to the extreme nature of their medical condition.	159.3 cm STANDARD_DEVIATION 7.7 • n=6 Participants • It was not possible to obtain accurate height measurements for several patients due to the extreme nature of their medical condition.	161.3 cm STANDARD_DEVIATION 7.6 • n=14 Participants • It was not possible to obtain accurate height measurements for several patients due to the extreme nature of their medical condition.
BMI	32.4 kg/m^2 STANDARD_DEVIATION 5.9 • n=8 Participants • It was not possible to calculate BMI for several patients due to the extreme nature of their medical condition.	33.2 kg/m^2 STANDARD_DEVIATION 5.7 • n=6 Participants • It was not possible to calculate BMI for several patients due to the extreme nature of their medical condition.	32.7 kg/m^2 STANDARD_DEVIATION 5.6 • n=14 Participants • It was not possible to calculate BMI for several patients due to the extreme nature of their medical condition.
Glasgow Coma Scale Score	5.6 units on a scale STANDARD_DEVIATION 2.7 • n=9 Participants	5.5 units on a scale STANDARD_DEVIATION 2.7 • n=8 Participants	5.5 units on a scale STANDARD_DEVIATION 2.6 • n=17 Participants
Rectal Temperature	41.8 Degrees Celsius STANDARD_DEVIATION 1.2 • n=9 Participants	41.3 Degrees Celsius STANDARD_DEVIATION 0.9 • n=8 Participants	41.5 Degrees Celsius STANDARD_DEVIATION 1.1 • n=17 Participants

PRIMARY outcome

Timeframe: 90 minutes post-randomization

Outcome measures

Outcome measures
Measure	Ryanodex and Standard of Care n=9 Participants In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered. Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push	Standard of Care Only (SOC) n=8 Participants Standard of Care treatment will consist of the immediate start of cooling measures. Standard of Care: Body cooling measures and supportive measures
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 [Time Frame: 90 Minutes Post-randomization]	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Treatment duration, up to 6 hours

Population: the outcome measure data table below is a summary of results showing the cumulative proportion of subjects achieving GCS score ≥13 post-randomization at all planned time points. Data is cumulative therefore the counts in the categories below will not add up to the Number Analyzed. score ≥ 13 post-randomization at all planned time points in the study is shown

Outcome measures

Outcome measures
Measure	Ryanodex and Standard of Care n=9 Participants In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered. Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push	Standard of Care Only (SOC) n=8 Participants Standard of Care treatment will consist of the immediate start of cooling measures. Standard of Care: Body cooling measures and supportive measures
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 after 45 min. post-randomization	1 Participants	0 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 after 75 min. post-randomization	3 Participants	2 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ to 13 after 2 hr.. post-randomization	5 Participants	2 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 at end of study or early termination	5 Participants	2 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 at 15 min post-randomization	1 Participants	0 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 at 30 min. post-randomization	1 Participants	0 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 after 60 min. post-randomization	2 Participants	1 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 after 90 min. post-randomization	4 Participants	2 Participants
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] Pts. achieving GCS score ≥ 13 after 4 hr. post-randomization/follow-up phase	5 Participants	2 Participants

Adverse Events

Ryanodex and Standard of Care

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Standard of Care Only (SOC)

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ryanodex and Standard of Care n=9 participants at risk In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered. Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push	Standard of Care Only (SOC) n=8 participants at risk Standard of Care treatment will consist of the immediate start of cooling measures. Standard of Care: Body cooling measures and supportive measures
Nervous system disorders Seizure	0.00% 0/9 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	12.5% 1/8 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	12.5% 1/8 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Investigations Coma Scale Abnormal	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.

Other adverse events

Other adverse events
Measure	Ryanodex and Standard of Care n=9 participants at risk In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered. Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push	Standard of Care Only (SOC) n=8 participants at risk Standard of Care treatment will consist of the immediate start of cooling measures. Standard of Care: Body cooling measures and supportive measures
Gastrointestinal disorders Diarrhoea	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Gastrointestinal disorders Nausea	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Investigations Coma Scale Abnormal	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Investigations Haemoglobin decreased	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Metabolism and nutrition disorders Acidosis	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Metabolism and nutrition disorders Hyperglycaemia	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/9 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	12.5% 1/8 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Nervous system disorders Seizure	0.00% 0/9 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	37.5% 3/8 • Number of events 3 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Nervous system disorders Agitation	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	12.5% 1/8 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Vascular disorders Hypertension	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.
Vascular disorders Hypotension	11.1% 1/9 • Number of events 1 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.	0.00% 0/8 • Adverse events data was collected from time of randomization through end of study (6 hours post-randomization) or early termination.

Additional Information

Chief Medical Officer

Eagle Pharmaceuticals, Inc.

Phone: 201-326-5300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PIs are not permitted to discuss or publish study results.
Publication restrictions are in place

Restriction type: OTHER