Efficacy and Safety Study of Ryanodex as Adjuvant Treatment in Subjects With Psychostimulant Drug-Induced Toxicity (PDIT)

NCT03189433 — Phase 2, Terminated, 2 participants, Eagle Pharmaceuticals, Inc.

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Phase 2, Multiple-Site, Open-Label, Randomized, 2-Group, Parallel Study to Assess the Efficacy and Safety of Ryanodex(R) (EGL-4101)as Adjuvant Treatment in Subjects With Psychostimulant Drug-Induced Toxicity (PDIT)

Registry	NCT03189433
Status	Terminated - Limited enrollment
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: none, treatment
Enrollment	2 (Actual)
Sponsor	Eagle Pharmaceuticals, Inc. (Industry)
Conditions	Drug Toxicity Psychotropic Agents Psychostimulants
Interventions	Ryanodex (dantrolene sodium) for injectable suspension (Drug)
Dates	start 2017-08-12, primary completion 2018-12-31, completion 2018-12-31, first posted 2017-06-16, last updated 2021-03-30
Locations	1 site in United States

-Summary

Ryanodex is being investigated as a potential adjuvant treatment for people suffering from psychostimulant drug-induced toxicity (PDIT), a life-threatening medical condition that results mainly from the abuse of certain illicit drugs, most notably methamphetamine, and related forms (MDMC or "Molly"; MDMA or "Ecstasy"). Ryanodex is approved for the treatment of malignant hyperthermia in conjunction with appropriate supportive measures and for prevention of malignant hyperthermia in patients at high risk and in this study, will be investigated for the treatment of PDIT. The hypothesis of this study is that administration of Ryanodex as adjuvant treatment to Standard of Care (SOC) will improve the clinical outcome compared with SOC alone, in subjects with psychostimulant drug induced toxicity. Current SOC is defined as body cooling and supportive measures.

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+Detailed description

This study will be conducted at pre-hospital emergency care (PHEC) facilities. The PHECs are medical units that are fully equipped and staffed to provide adequate emergency medical care to patients with PDIT. The study is designed to evaluate the safety and efficacy of Ryanodex in an on0site pre-hospital emergency setting where subjects are anticipated to be treated over a short period of time and then transferred to another medical facility or released. After screening and diagnosis of PDIT, SOC treatment will be initiated. Subjects eligible for the study will be randomized to either receive SOC + Ryanodex or to receive SOC only. Study subjects are expected to remain at the study site for a maximum of 6 hours post-baseline.

+Arms and interventions

Arm	Type	Interventions	Description
Ryanodex + Standard of Care	Active comparator	Drug: Ryanodex (dantrolene sodium) for injectable suspension	Ryanodex (dantrolene sodium) 50 mg/mL suspension to be administered as a rapid IV push of 2.5 mg/kg, added to Standard of Care (SOC). SOC is defined as efficient body cooling by physical methods and supportive measures \[ice packs, evaporative cooling(application of room temperature water via mist with use of a fan\], benzodiazepines to ameliorate shivering, IV fluids, respiratory support, and other treatments deemed necessary to treat complications or comorbidities\]. Administer a single dose of Ryanodex. If a subject does not show an adequate clinical response within 10 - 30 minutes post-dose, a second IV bolus dose of 2.5 mg/kg may be administered.
Standard of Care only (SOC)	No intervention		Standard of Care is defined as efficient body cooling by physical methods and supportive methods and supportive measures\[ice packs, evaporative cooling (application of room temperature water via mist with use of a fan\], benzodiazepines to ameliorate shivering, IV fluids, respiratory support, and other treatments deemed necessary to treat complications or comorbidities\].

Ryanodex (dantrolene sodium) for injectable suspension (Drug): Ryanodex (dantrolene sodium) for injectable suspension, 250 mg/vial to be reconstituted in 5 mL of sterile water for injection to yield a 50 mg/mL suspension that will be administered as a rapid IV push of 2.5 mg/mL.

+Outcome measures

Primary outcomes

Proportion of Subjects Who Achieved a Logistic Organ Dysfuction System (LODS) Total Score Less Than or Equal to 5 [At or prior to 60 minutes post-randomization]: Logistic Organ Dysfunction System (LODS) score (measure/scoring of 1-3 specific parameters in 6 organ systems; neurologic, cardiologic, renal, pulmonary, hematologic, and hepatic). One to 5 LODS points are assigned to the levels of severity and the resulting LODS scores range can range from 0 to 22 points. A lower score represents a better outcome; a score of 0 points is a better outcome than a score o 22 points.

Secondary outcomes

Proportion of Subjects Who Achieved a LODS Total Score Less Than or Equal to 5 at Other Planned Time Points. [Up to 6 hours post-dose.]: Proportion of subjects who achieved a LODS total score less than or equal to 5 at other planned time points. One to 5 LODS points are assigned to the levels of severity and the resulting LODS scores range can range from 0 to 22 points. A lower score represents a better outcome.

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria: Male and non-pregnant subjects diagnosed with psychostimulant drug induced toxicity as evidenced by all of the following: core body temperature of greater than or equal to 39.5 degrees C; organ dysfunction, as evidenced by a Logistic Organ Dysfunction System score of greater than or equal to 6 (In the event of any delay in obtaining the results for baseline LODS score determination, subject may be enrolled. After enrollment, if the pending baseline LODS score turns out to be less than 6, the subject will be withdrawn from the study and replaced); known or suspected us of a psychostimulant drug in the judgment of the Investigator; negative blood pregnancy test for females (in the event of any delay in obtaining pregnancy test result, subject may be enrolled and randomized if all of the other eligibility criteria are met).

Exclusion Criteria: Diagnosed with or is suspected to have an acute, clinically severe infection, which may, in the opinion of the Investigator, may increase the subject's risk for participating in the study an/or may impair the ability of performing and/or interpreting study assessments; severe hyperthermia secondary to a condition other than a psychostimulant drug-induced toxicity; likelihood of head trauma in the past 3 months, or other systemic disease that might increase the subject's risk for participating in the study and/or may impair the ability of performing and/or interpreting study assessments; positive pregnancy test or evidence of active lactation; known history of allergy or hypersensitivity to dantrolene; known history of seizure disorders or epilepsy; current or prior use (within the past 2 weeks) of calcium channel blockers.

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+Posted results

Participant flow

Milestone	Ryanodex + Standard of Care	Standard of Care Only (SOC)
Started	2	0
Completed	0	0
Not completed	2	0

Outcome results

Proportion of Subjects Who Achieved a Logistic Organ Dysfuction System (LODS) Total Score Less Than or Equal to 5 (Primary)
Proportion of Subjects Who Achieved a LODS Total Score Less Than or Equal to 5 at Other Planned Time Points. (Secondary)

Adverse events

Time frame: NA: No adverse event data were collected; time frame is 0 hours, 0 days, 0 months.

Arm	Deaths	Serious adverse events	Other adverse events
Ryanodex + Standard of Care	0	0	0
Standard of Care Only (SOC)	0	0	0

+Locations (1)

Facility	City	Country	Status
CrowdRx Medical Office- Moonrise Festival	Baltimore, Maryland	United States

+Study documents

Statistical Analysis Plan (PDF, 2017-09-06)
Study Protocol (PDF, 2017-09-06)

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