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Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection

Primary Purpose

Acetaminophen Overdose

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)
Acetadote
Sponsored by
Cumberland Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acetaminophen Overdose focused on measuring Acetaminophen overdose; induced hepatotoxicity, liver injury

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Maricopa Medical Center
  • Loma Linda University Medical Center
  • University of California Irvine Medical Center
  • UCSD Medical Center
  • University of Colorado Hospital
  • Denver Health and Hospital Authority
  • Hartford Hospital
  • LSU Health Sciences Center - Shreveport
  • Beth Israel Deaconess Medical Center
  • UMass Memorial Medical Center
  • Spectrum Health Butterworth Hospital
  • East Carolina University Medical Center
  • Toledo Hospital
  • Scott & White Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Acetadote without EDTA

Acetadote

Arm Description

Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free]

Acetadote [Old formulation containing EDTA]

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
To Evaluate the Incidence of Treatment Emergent Adverse Events
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.

Full Information

First Posted
May 4, 2010
Last Updated
August 1, 2014
Sponsor
Cumberland Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01118663
Brief Title
Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection
Official Title
A Multi-center, Double-blind, Randomized, Controlled Study to Determine the Efficacy and Safety of a New Formulation of Acetylcysteine Injection
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Terminated
Study Start Date
September 2010 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cumberland Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acetaminophen Overdose
Keywords
Acetaminophen overdose; induced hepatotoxicity, liver injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acetadote without EDTA
Arm Type
Experimental
Arm Description
Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free]
Arm Title
Acetadote
Arm Type
Active Comparator
Arm Description
Acetadote [Old formulation containing EDTA]
Intervention Type
Drug
Intervention Name(s)
Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) - Free)
Other Intervention Name(s)
acetylcysteine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Acetadote
Other Intervention Name(s)
acetylcysteine
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
Time Frame
21 hours
Secondary Outcome Measure Information:
Title
To Evaluate the Percentage of Subjects Requiring Continued Therapy
Description
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
Time Frame
21 hours
Title
To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen.
Description
Because the study was terminated prematurely due to lack of enrollment, there was an insufficient sample size to conduct an efficacy analysis.
Time Frame
42 hours
Title
To Evaluate the Incidence of Treatment Emergent Adverse Events
Time Frame
21-42 hours
Title
To Evaluate the Incidence of Anaphylactoid Reaction.
Description
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.
Time Frame
1 hour

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Art Wheeler, MD
Organizational Affiliation
Cumberland Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Maricopa Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85008
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92350
Country
United States
Facility Name
University of California Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
UCSD Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Denver Health and Hospital Authority
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
LSU Health Sciences Center - Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71130
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
UMass Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Spectrum Health Butterworth Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
44506
Country
United States
Facility Name
East Carolina University Medical Center
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Toledo Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Scott & White Medical Center
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9536427
Citation
Bhushan M, Beck MH. Allergic contact dermatitis from disodium ethylenediamine tetra-acetic acid (EDTA) in a local anaesthetic. Contact Dermatitis. 1998 Mar;38(3):183. doi: 10.1111/j.1600-0536.1998.tb05702.x. No abstract available.
Results Reference
background
PubMed Identifier
9452326
Citation
van Laar T, van Hilten B, Neef C, Rutgers AW, Pavel S, Bruijn JA. The role of EDTA in provoking allergic reactions to subcutaneous infusion of apomorphine in patients with Parkinson's disease: a histologic study. Mov Disord. 1998 Jan;13(1):52-5. doi: 10.1002/mds.870130113.
Results Reference
background
PubMed Identifier
10617216
Citation
Kimura M, Kawada A. Contact dermatitis due to trisodium ethylenediaminetetra-acetic acid (EDTA) in a cosmetic lotion. Contact Dermatitis. 1999 Dec;41(6):341. doi: 10.1111/j.1600-0536.1999.tb06184.x. No abstract available.
Results Reference
background
PubMed Identifier
15579060
Citation
Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. doi: 10.2174/1381612043382846.
Results Reference
background

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Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection

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