Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection

Phase 3

Terminated

• Conditions: Acetaminophen Overdose
• Interventions: Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free); Drug: Acetadote

• Registration Number: NCT01118663
• Lead Sponsor: Cumberland Pharmaceuticals

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2010-05-04
• Study First Submitted QC: 2010-05-05
• Study First Posted: 2010-05-07
• Study Start: 2010-09
• Primary Completion: 2012-11
• Study Completion: 2013-05
• Results First Submitted: 2014-04-15
• Status Verified: 2014-08
• Results First Submitted QC: 2014-08-01
• Last Update Submitted: 2014-08-01
• Results First Posted: 2014-08-04
• Last Update Posted: 2014-08-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

1. Any subject requiring treatment with acetylcysteine for acute acetaminophen toxicity

Exclusion Criteria

1. History of allergy or hypersensitivity to acetylcysteine or any component of Acetadote.
2. Exposed to investigational drugs within 30 days before Clinical Trial Material (CTM) administration.
3. Pregnant or nursing.
4. Less than 12 years of age.
5. Have a baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1000 U/L.
6. Have a baseline International Normalized. Ratio (INR) > 2.0
7. 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.
8. 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.
9. 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).
10. Refusal to provide written authorization for use and disclosure of protected health information.
11. Be otherwise unsuitable for the study, in the opinion of the Investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acetadote without EDTA	Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)	Acetadote EF \[Ethylenediaminetetraacetic Acid (EDTA) - Free\]
Acetadote	Acetadote	Acetadote \[Old formulation containing EDTA\]

Primary Outcome Measures

Name	Time	Method
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	21 hours	Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.

Secondary Outcome Measures

Name	Time	Method
To Evaluate the Percentage of Subjects Requiring Continued Therapy	21 hours	Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen.	42 hours	Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
To Evaluate the Incidence of Treatment Emergent Adverse Events	21-42 hours
To Evaluate the Incidence of Anaphylactoid Reaction.	1 hour	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.

Trial Locations

Locations (14)

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

East Carolina University Medical Center; 🇺🇸 Greenville, North Carolina, United States

Toledo Hospital; 🇺🇸 Toledo, Ohio, United States

Scott & White Medical Center; 🇺🇸 Temple, Texas, United States

Maricopa Medical Center; 🇺🇸 Phoenix, Arizona, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

LSU Health Sciences Center - Shreveport; 🇺🇸 Shreveport, Louisiana, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

UMass Memorial Medical Center; 🇺🇸 Worcester, Massachusetts, United States

Spectrum Health Butterworth Hospital; 🇺🇸 Grand Rapids, Michigan, United States

University of California Irvine Medical Center; 🇺🇸 Orange, California, United States

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Denver Health and Hospital Authority; 🇺🇸 Denver, Colorado, United States

UCSD Medical Center; 🇺🇸 San Diego, California, United States