A Multi-center, Double-blind, Randomized, Controlled Study to Determine the Efficacy and Safety of a New Formulation of Acetylcysteine Injection
Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection
Sponsors
Source
Cumberland Pharmaceuticals
Oversight Info
Has Dmc
Yes
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.
Overall Status
Terminated
Start Date
2010-09-01
Completion Date
2013-05-01
Primary Completion Date
2012-11-01
Phase
Phase 3
Study Type
Interventional
Primary Outcome
Measure |
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 |
21 hours |
Secondary Outcome
Measure |
Time Frame |
|
To Evaluate the Percentage of Subjects Requiring Continued Therapy |
21 hours |
|
To Evaluate the Incidence of Clinical Need for Therapy Beyond the Current 21 Hour FDA Approved Dosing Regimen. |
42 hours |
|
To Evaluate the Incidence of Treatment Emergent Adverse Events |
21-42 hours |
|
To Evaluate the Incidence of Anaphylactoid Reaction. |
1 hour |
Enrollment
17
Condition
Intervention
Intervention Type
Drug
Intervention Name
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
Arm Group Label
Acetadote without EDTA
Other Name
acetylcysteine
Intervention Type
Drug
Intervention Name
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.
Arm Group Label
Acetadote
Other Name
acetylcysteine
Eligibility
Criteria
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.
Gender
All
Minimum Age
12 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Art Wheeler, MD |
Study Director |
Cumberland Pharmaceuticals Inc |
Location
Facility |
|
Maricopa Medical Center Phoenix Arizona 85008 United States |
|
Loma Linda University Medical Center Loma Linda California 92350 United States |
|
University of California Irvine Medical Center Orange California 92868 United States |
|
UCSD Medical Center San Diego California 92103 United States |
|
University of Colorado Hospital Aurora Colorado 80045 United States |
|
Denver Health and Hospital Authority Denver Colorado 80204 United States |
|
Hartford Hospital Hartford Connecticut 06102 United States |
|
LSU Health Sciences Center - Shreveport Shreveport Louisiana 71130 United States |
|
Beth Israel Deaconess Medical Center Boston Massachusetts 02215 United States |
|
UMass Memorial Medical Center Worcester Massachusetts 01655 United States |
|
Spectrum Health Butterworth Hospital Grand Rapids Michigan 44506 United States |
|
East Carolina University Medical Center Greenville North Carolina 27834 United States |
|
Toledo Hospital Toledo Ohio 43606 United States |
|
Scott & White Medical Center Temple Texas 76508 United States |
Location Countries
Country
United States
Verification Date
2014-08-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keyword
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Intervention Browse
Mesh Term
Acetylcysteine
N-monoacetylcystine
Pentetic Acid
Edetic Acid
Arm Group
Arm Group Label
Acetadote without EDTA
Arm Group Type
Experimental
Description
Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free]
Arm Group Label
Acetadote
Arm Group Type
Active Comparator
Description
Acetadote [Old formulation containing EDTA]
Firstreceived Results Date
N/A
Reference
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.
PMID
9536427
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.
PMID
9452326
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.
PMID
10617216
Citation
Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. Review.
PMID
15579060
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Study First Submitted
May 4, 2010
Study First Submitted Qc
May 5, 2010
Study First Posted
May 7, 2010
Last Update Submitted
August 1, 2014
Last Update Submitted Qc
August 1, 2014
Last Update Posted
August 4, 2014
Results First Submitted
April 15, 2014
Results First Submitted Qc
August 1, 2014
Results First Posted
August 4, 2014
ClinicalTrials.gov processed this data on August 29, 2018
Conditions
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Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.