To Evaluate the Efficacy and Safety of TYNADOTE® in the Treatment of Acetaminophen Overdose
Primary Purpose
Hepatitis
Status
Recruiting
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
TYNADOTE
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis focused on measuring Paracetamol, Acetaminophen, Acute liver failure, N-acetylcysteine, Acetaminophen overdose
Eligibility Criteria
Inclusion Criteria:
- Poisoning and hospitalized patients taking acetaminophen.
- Acute ingestion of more than 150 mg/kg or plasma concentration of Acetaminophen is above the treatment line on single acute acetaminophen overdose nomogram.
- Male or female with age more than 20 years at Screening.
- Ability and willingness to provide informed consent, adhere to the study visit schedule and complete all study assessments.
Exclusion Criteria:
- Subjects with Sequential Organ Failure Assessment (SOFA) Score higher than 12.
- Subjects who fulfilled the King's College Hospital (KCH) Criteria for liver transplantation.
- Subjects who was conscious disturbance.
- History of allergic response(s) to N-acetylcysteine (NAC), mannitol, sucralose or related drugs.
- Subject who was unable to take medicine by oral route.
- Receiving any investigational drug within 30 days prior to first dosing.
- Subject who had attacked asthma or bronchitis combined with medication therapy within six months prior to enrollment.
- Donating greater than 150 mL of blood within two months prior to first dosing or donating plasma (e.g. plasmapheresis) within 14 days prior to first dosing. All subjects will be advised not to donate blood for four weeks after completing the study.
- Subject is pregnant or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test at baseline.
- Anuria, pulmonary congestion, severe congestive heart failure, brain hemorrhage, or any conditions that in the opinion of the investigator may interfere with the evaluation of study objectives.
- The combination of poisoning contains acetaminophen and other compound.
- Body weight less than 50 kg.
Sites / Locations
- Taipei Veterans General HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Test drug
Placebo
Arm Description
200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
Outcomes
Primary Outcome Measures
Alanine aminotransferase
Percentage change from baseline of ALT at Day 3.
Secondary Outcome Measures
Alanine aminotransferase
Percentage change from baseline of ALT at Day 7
Alanine aminotransferase
Percentage change from baseline of AST at Day 3, Day 7
Total bilirubin
Incidence of total bilirubin > 2.5mg/dL at Day 3, Day 7, Day 21
Inte- rnational Normalize Ratio
Incidence of INR > 1.25 at Day 3, Day 7, Day 21
Aspartate aminotransferase or Alanine aminotransferase
Incidence of AST or ALT >1000 U/L at Day 3, Day 7, Day 21
Hepatic failure rate (hepatic encephalopathy, ascites, total bilirubin, INR or liver transplantation)
Hepatic failure rate (hepatic encephalopathy, ascites, total bilirubin >2.5mg/dL, INR >1.25, or liver transplantation) at Day 7, Day 21
Mortality rate
Mortality rate at Day 7, Day 21
Free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts
The time-interval weighted area under the curve (AUC) of free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts within 72-hour treatment period
TYNADOTE® plasma concentration
The time-interval weighted area under the curve (AUC) of TYNADOTE® plasma concentration during 72-hour treatment period
Full Information
NCT ID
NCT05557448
First Posted
September 22, 2022
Last Updated
July 17, 2023
Sponsor
Sinew Pharma Inc.
Collaborators
Taipei Veterans General Hospital, Taiwan
1. Study Identification
Unique Protocol Identification Number
NCT05557448
Brief Title
To Evaluate the Efficacy and Safety of TYNADOTE® in the Treatment of Acetaminophen Overdose
Official Title
An Exploratory Study to Evaluate the Efficacy and Safety of TYNADOTE® Combined N-acetylcysteine in the Treatment of Acetaminophen Overdose
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sinew Pharma Inc.
Collaborators
Taipei Veterans General Hospital, Taiwan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the efficacy and safety of TYNADOTE® in the treatment of acetaminophen overdose
Detailed Description
This will be a 21-day study to evaluate the efficacy and safety of TYNADOTE® in the treatment of acetaminophen overdose.
After the inform consent is obtained from the subject or his/her legal guardians, the designated assessment will be performed. Subjects who fulfill all the inclusion and exclusion criteria will be eligible to enter the study. Except standard NAC antidote therapy, subjects would be randomized as 1:1 ratio to combine oral TYNADOTE® or placebo.
Eligible subjects will be randomized to receive oral TYNADOTE®/placebo combined iv NAC, and the regimen was listed as below:
The NAC intravenous loading dose is 150 mg/kg over a period of 15 to 60 minutes, followed by an infusion of 12.5 mg/kg per hour over a 4-hour period, and finally an infusion of 6.25 mg/kg per hour over a 16-hour period. Study drug, TYNADOTE® /placebo, should be given a loading dose of 400 mg, followed by 17 maintenance doses of 200 mg every 4 hours (Day 1 to Day 3).
During the treatment period, vital signs will be checked 15 minutes prior to dosing, 30 minutes, 60 minutes, then 2, 4, 8, 12, 24, 36, 48, 60 and 72 hours after first dosing. Blood samples will be collected for liver injuries and function test, including AST, ALT, total bilirubin, direct bilirubin and prothrombin time (INR), prior to dosing, 4 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours after first dosing. Blood samples for drug/metabolites concentration, including TYNADOTE® plasma concentration (trough level), plasma acetaminophen concentration, AAP-Cys and AAP-Cys adducts concentration, prior to dosing, 4 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours and 72 hours after first dosing. Blood samples for biochemistry and hematology, Day 1-3.
After completing the treatment (Day 3), subject will conduct the following evaluations before discharge:
Review of adverse events
Review of concomitant medications
Physical examination On Day 7 and Day 21, subjects should return to the clinics for liver injuries/function follow up and reviewing the adverse events.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis
Keywords
Paracetamol, Acetaminophen, Acute liver failure, N-acetylcysteine, Acetaminophen overdose
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
test drug
Masking
ParticipantInvestigator
Masking Description
placebo
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Test drug
Arm Type
Active Comparator
Arm Description
200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
Intervention Type
Drug
Intervention Name(s)
TYNADOTE
Intervention Description
Subjects will take 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Subjects will take 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
Primary Outcome Measure Information:
Title
Alanine aminotransferase
Description
Percentage change from baseline of ALT at Day 3.
Time Frame
Day 3
Secondary Outcome Measure Information:
Title
Alanine aminotransferase
Description
Percentage change from baseline of ALT at Day 7
Time Frame
Day 7
Title
Alanine aminotransferase
Description
Percentage change from baseline of AST at Day 3, Day 7
Time Frame
Day 7
Title
Total bilirubin
Description
Incidence of total bilirubin > 2.5mg/dL at Day 3, Day 7, Day 21
Time Frame
Day 3, Day 7 and Day 21
Title
Inte- rnational Normalize Ratio
Description
Incidence of INR > 1.25 at Day 3, Day 7, Day 21
Time Frame
Day 3, Day 7 and Day 21
Title
Aspartate aminotransferase or Alanine aminotransferase
Description
Incidence of AST or ALT >1000 U/L at Day 3, Day 7, Day 21
Time Frame
Day 3, Day 7 and Day 21
Title
Hepatic failure rate (hepatic encephalopathy, ascites, total bilirubin, INR or liver transplantation)
Description
Hepatic failure rate (hepatic encephalopathy, ascites, total bilirubin >2.5mg/dL, INR >1.25, or liver transplantation) at Day 7, Day 21
Time Frame
Day 7 and Day 21
Title
Mortality rate
Description
Mortality rate at Day 7, Day 21
Time Frame
Day 7 and Day 21
Title
Free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts
Description
The time-interval weighted area under the curve (AUC) of free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts within 72-hour treatment period
Time Frame
Day 1-3
Title
TYNADOTE® plasma concentration
Description
The time-interval weighted area under the curve (AUC) of TYNADOTE® plasma concentration during 72-hour treatment period
Time Frame
Day 1-3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Poisoning and hospitalized patients taking acetaminophen.
Acute ingestion of more than 150 mg/kg or plasma concentration of Acetaminophen is above the treatment line on single acute acetaminophen overdose nomogram.
Male or female with age more than 20 years at Screening.
Ability and willingness to provide informed consent, adhere to the study visit schedule and complete all study assessments.
Exclusion Criteria:
Subjects with Sequential Organ Failure Assessment (SOFA) Score higher than 12.
Subjects who fulfilled the King's College Hospital (KCH) Criteria for liver transplantation.
Subjects who was conscious disturbance.
History of allergic response(s) to N-acetylcysteine (NAC), mannitol, sucralose or related drugs.
Subject who was unable to take medicine by oral route.
Receiving any investigational drug within 30 days prior to first dosing.
Subject who had attacked asthma or bronchitis combined with medication therapy within six months prior to enrollment.
Donating greater than 150 mL of blood within two months prior to first dosing or donating plasma (e.g. plasmapheresis) within 14 days prior to first dosing. All subjects will be advised not to donate blood for four weeks after completing the study.
Subject is pregnant or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test at baseline.
Anuria, pulmonary congestion, severe congestive heart failure, brain hemorrhage, or any conditions that in the opinion of the investigator may interfere with the evaluation of study objectives.
The combination of poisoning contains acetaminophen and other compound.
Body weight less than 50 kg.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ChengHuei Mr. Hsiong, Vice President
Phone
+886-2-2788-5365
Email
info@sinewpharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
WanLing Ms. Yang, Research
Phone
+886-2-2788-5365
Email
wlyang@sinewpharma.com
Facility Information:
Facility Name
Taipei Veterans General Hospital
City
Taipei City
State/Province
Beitou District
ZIP/Postal Code
11217
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ChengHuei Mr Hsiong, Vice President
Phone
+886-2-2788-5365
Email
info@sinewpharma.com
First Name & Middle Initial & Last Name & Degree
WanLing Ms Yang, Research
Phone
+886-2-2788-5365
Email
wlyang@sinewpharma.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
To Evaluate the Efficacy and Safety of TYNADOTE® in the Treatment of Acetaminophen Overdose
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