Safety and Efficacy Study of a New Formulation of Acetylcysteine Injection

Acetaminophen Overdose Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01118663
• Other study ID #: CPI-NAC-001
• Status: Terminated
• Phase: Phase 3
• First received: May 4, 2010
• Last updated: August 1, 2014
• Start date: September 2010
• Est. completion date: May 2013

Study information

• Verified date: August 2014
• Source: Cumberland Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: May 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acetaminophen Overdose

Intervention

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
• 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.

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Denver Health and Hospital Authority	Denver	Colorado
United States	Spectrum Health Butterworth Hospital	Grand Rapids	Michigan
United States	East Carolina University Medical Center	Greenville	North Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Loma Linda University Medical Center	Loma Linda	California
United States	University of California Irvine Medical Center	Orange	California
United States	Maricopa Medical Center	Phoenix	Arizona
United States	UCSD Medical Center	San Diego	California
United States	LSU Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	Scott & White Medical Center	Temple	Texas
United States	Toledo Hospital	Toledo	Ohio
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Cumberland Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	To Evaluate the Incidence of Treatment Emergent Adverse Events		21-42 hours	Yes
Secondary	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	Yes