HepatitisPhase 2NCT05557448
To Evaluate the Efficacy and Safety of TYNADOTE® in the Treatment of Acetaminophen Overdose
A Phase 2 study testing TYNADOTE in people with Hepatitis, run by Sinew Pharma Inc. at 1 site in Taiwan.
Trial summary
To evaluate the efficacy and safety of TYNADOTE® in the treatment of acetaminophen overdose Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Hepatitis
- What is being tested?
- TYNADOTE
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 May 2023to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Veterans General Hospital
Taipei, Beitou District, 11217
ChengHuei Mr Hsiong, Vice President, +886-2-2788-5365, info@sinewpharma.com
WanLing Ms Yang, Research, +886-2-2788-5365, wlyang@sinewpharma.com
About this study
Official title: An Exploratory Study to Evaluate the Efficacy and Safety of TYNADOTE® Combined N-acetylcysteine in the Treatment of Acetaminophen Overdose
To evaluate the efficacy and safety of TYNADOTE® in the treatment of acetaminophen overdose
Read the 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.
- Conditions
- Hepatitis
- Being tested
- TYNADOTE, Placebo Oral Tablet
- Keywords
- Paracetamol, Acetaminophen, Acute liver failure, N-acetylcysteine, Acetaminophen overdose
- Medical subject headings
- Hepatitis, Liver Failure, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TYNADOTEDrug
Subjects will take 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
Placebo Oral TabletDrug
Subjects will take 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses
| Study group | Role | What they receive |
|---|---|---|
| Test drug | Active comparator | 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses Receives: Drug: TYNADOTE |
| Placebo | Placebo comparator | 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alanine aminotransferase
Percentage change from baseline of ALT at Day 3.
Measured: Day 3
Secondary outcomes (9)
Alanine aminotransferase
Percentage change from baseline of ALT at Day 7
Measured: Day 7
Alanine aminotransferase
Percentage change from baseline of AST at Day 3, Day 7
Measured: Day 7
Total bilirubin
Incidence of total bilirubin > 2.5mg/dL at Day 3, Day 7, Day 21
Measured: Day 3, Day 7 and Day 21
Inte- rnational Normalize Ratio
Incidence of INR > 1.25 at Day 3, Day 7, Day 21
Measured: Day 3, Day 7 and Day 21
Aspartate aminotransferase or Alanine aminotransferase
Incidence of AST or ALT >1000 U/L at Day 3, Day 7, Day 21
Measured: Day 3, Day 7 and 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
Measured: Day 7 and Day 21
Mortality rate
Mortality rate at Day 7, Day 21
Measured: Day 7 and 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
Measured: Day 1-3
TYNADOTE® plasma concentration
The time-interval weighted area under the curve (AUC) of TYNADOTE® plasma concentration during 72-hour treatment period
Measured: Day 1-3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2022
- Study start1 May 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- test drug
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sinew Pharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Taipei Veterans General Hospital, Taiwan
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05557448
- Sponsor's protocol ID
- TYNADOTE-2-001
- Status last verified
- Jan 2024
- First submitted
- 22 Sep 2022
- Last updated
- 10 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study to Evaluate the Efficacy and Safety of TYNADOTE® Combined N-acetylcysteine in the Treatment of Acetaminophen Overdose
- ClinicalTrials.gov ID
- NCT05557448
- Acronym / sponsor ID
- TYNADOTE-2-001
- Conditions
- Hepatitis
- Keywords
- Paracetamol, Acetaminophen, Acute liver failure, N-acetylcysteine, Acetaminophen overdose
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Sinew Pharma Inc.Industry (pharma, biotech, devices)
- Collaborators
- Taipei Veterans General Hospital, Taiwan
- Study start
- 1 May 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- test drug
| Arm | Type | Receives |
|---|---|---|
| Test drug | Active comparator | Drug: TYNADOTE200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses |
| Placebo | Placebo comparator | Drug: Placebo Oral Tablet200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TYNADOTESubjects will take 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses | Drug | Test drug |
| Placebo Oral TabletSubjects will take 200 mg/every 4 hours, with a loading dose (400 mg) and then followed by 17 maintenance doses | Drug | Placebo |
Primary outcome
Alanine aminotransferase
Time frame: Day 3
Percentage change from baseline of ALT at Day 3.
9 secondary outcomes
Alanine aminotransferase
Time frame: Day 7
Alanine aminotransferase
Time frame: Day 7
Total bilirubin
Time frame: Day 3, Day 7 and Day 21
Inte- rnational Normalize Ratio
Time frame: Day 3, Day 7 and Day 21
Aspartate aminotransferase or Alanine aminotransferase
Time frame: Day 3, Day 7 and Day 21
Hepatic failure rate (hepatic encephalopathy, ascites, total bilirubin, INR or liver transplantation)
Time frame: Day 7 and Day 21
Mortality rate
Time frame: Day 7 and Day 21
Free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts
Time frame: Day 1-3
TYNADOTE® plasma concentration
Time frame: Day 1-3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TYNADOTE in people with Hepatitis, run by Sinew Pharma Inc. at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ChengHuei Mr. Hsiong, Vice President (+886-2-2788-5365, info@sinewpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alanine aminotransferase (time frame: Day 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2024.