Acetaminophen Overdose
Conditions
Keywords
Acetaminophen overdose; induced hepatotoxicity, liver injury
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.
Interventions
DRUGAcetadote 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
DRUGAcetadote
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.
Sponsors
Cumberland Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acetadote Without EDTA Acetadote EF \[Ethylenediaminetetraacetic Acid (EDTA) - Free\]
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 | 7 |
| Acetadote Acetadote \[Old formulation containing EDTA\]
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. | 10 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Acetadote Without EDTA | Acetadote | Total |
|---|---|---|---|
| Age, Customized ≤ 18 years | 1 participants | 0 participants | 1 participants |
| Age, Customized 19-59 years | 6 participants | 8 participants | 14 participants |
| Age, Customized ≥ 60 years | 0 participants | 2 participants | 2 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 15 Participants |
| Region of Enrollment United States | 7 participants | 10 participants | 17 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 7 / 10 |
| serious Total, serious adverse events | 0 / 7 | 0 / 10 |
Outcome results
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.
Time frame: 21 hours
Population: Because the study was terminated prematurely due to lack of enrollment, there was insufficient sample size to conduct efficacy analysis.
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.
Time frame: 1 hour
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetadote Without EDTA | To Evaluate the Incidence of Anaphylactoid Reaction. | 0 participants |
| Acetadote | To Evaluate the Incidence of Anaphylactoid Reaction. | 1 participants |
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.
Time frame: 42 hours
Population: Because the study was terminated prematurely due to lack of enrollment, there was insufficient sample size to conduct efficacy analysis.
Secondary
To Evaluate the Incidence of Treatment Emergent Adverse Events
Time frame: 21-42 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Acetadote Without EDTA | To Evaluate the Incidence of Treatment Emergent Adverse Events | 13 Number of Events |
| Acetadote | To Evaluate the Incidence of Treatment Emergent Adverse Events | 14 Number of Events |
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.
Time frame: 21 hours
Population: Because the study was terminated prematurely due to lack of enrollment, there was insufficient sample size to conduct efficacy analysis.