Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 2012

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.

Interventions

  • Drug: Acetadote EF (Ethylenediaminetetraacetic Acid (EDTA) – Free)
    • 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
  • Drug: Acetadote
    • 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.

Arms, Groups and Cohorts

  • Experimental: Acetadote without EDTA
    • Acetadote EF [Ethylenediaminetetraacetic Acid (EDTA) - Free]
  • Active Comparator: Acetadote
    • Acetadote [Old formulation containing EDTA]

Clinical Trial Outcome Measures

Primary 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
    • Time Frame: 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 Measures

  • To Evaluate the Percentage of Subjects Requiring Continued Therapy
    • Time Frame: 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.
    • Time Frame: 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
    • Time Frame: 21-42 hours
  • To Evaluate the Incidence of Anaphylactoid Reaction.
    • Time Frame: 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.

Participating in This Clinical Trial

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 Eligibility: All

Minimum Age: 12 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Cumberland Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Art Wheeler, MD, Study Director, Cumberland Pharmaceuticals, Inc.

References

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.

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.

Kimura M, Kawada A. Contact dermatitis due to trisodium ethylenediaminetetra-acetic acid (EDTA) in a cosmetic lotion. Contact Dermatitis. 1999 Dec;41(6):341.

Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. Review.

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