Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection

Study Overview
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Brief Summary
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The primary purpose of this study is determine if a new formulation of Acetadote is at least as effective as the current formulation in the prevention and treatment of acetaminophen overdose related liver injury.

Detailed Description
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The primary objective of this study is to demonstrate non-inferiority of efficacy determined by the proportion of subjects who develop hepatotoxicity when treated with a new formulation of Acetadote and the proposed new dosing regimen compared to the rate of hepatotoxicity with the current formulation of Acetadote and the current dosing regimen.

Official Title
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A Multi-center, Double-blind, Randomized, Controlled Study to Determine the Efficacy and Safety of a New Formulation of Acetylcysteine Injection

Conditions
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Acetaminophen Overdose

Intervention / Treatment
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* Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)
* Drug: Acetadote


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Any subject requiring treatment with acetylcysteine for acute acetaminophen toxicity Exclusion Criteria: History of allergy or hypersensitivity to acetylcysteine or any component of Acetadote. Exposed to investigational drugs within 30 days before Clinical Trial Material (CTM) administration. Pregnant or nursing. Less than 12 years of age. Have a baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1000 U/L. Have a baseline International Normalized. Ratio (INR) > 2.0 Be on dialysis or having existing renal injury such that the volume of the study drug administration would render the patient unsuitable for the study, in the opinion of the investigator. Have congestive heart failure such that the volume of the study drug administration would render the patient unsuitable for the study, in the opinion of the investigator. Inability to understand the requirements of the study. Subjects must be willing to provide written informed consent or consent of parent/legal guardian (as evidenced by signature on an informed consent document approved by an Institutional Review Board [IRB]), and agree to abide by the study restrictions. (If the subject is incapacitated, informed consent will be sought from a legally acceptable representative). Refusal to provide written authorization for use and disclosure of protected health information. Be otherwise unsuitable for the study, in the opinion of the Investigator.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetadote without EDTA<br>Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free] | Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)<br>* Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free) {new formulation} 200 mg/kg in 1000 ml diluent over 4 hours; then 100 mg/kg in 1000 ml diluent over 16 hours<br>* Other names: acetylcysteine;|
| Active Comparator: Acetadote<br>Acetadote [Old formulation containing EDTA] | Drug: Acetadote<br>* Acetadote [old formulation] 150 mg/kg in 200 mL diluent over 60 minutes; then Acetadote 50 mg/kg in 500 mL diluent over 4 hours; then Acetadote 100 mg/kg in 1000 mL diluent over 16 hours.<br>* Other names: acetylcysteine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Hepatoxicity as Measured by the Percentage of Subjects With an Alanine Transaminase (ALT) or Aspartate Transaminase (AST) Value > 1000 U/L Versus Those With an ALT and AST < 1000 U/L | Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis. | 21 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Percentage of Subjects Requiring Continued Therapy | Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis. | 21 hours | 
| To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen. | Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis. | 42 hours | 
| To Evaluate the Incidence of Treatment Emergent Adverse Events |  | 21-42 hours | 
| To Evaluate the Incidence of Anaphylactoid Reaction. | Data analysis was conducted on the subjects enrolled in the study prior to study termination. Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis. | 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetaminophen overdose; induced hepatotoxicity, liver injury