Acetaminophen ToxicityNCT03451487
A Randomized, Single-blind, Parallel Group and Multiple - Dose Design Study
A study testing Panadol® and SafeTynadol® in people with Acetaminophen Toxicity, run by Sinew Pharma Inc. at 1 site in Taiwan.
Trial summary
To investigate and compare the possible response of Panadol® and SafeTynadol® formulations in healthy volunteers. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Acetaminophen Toxicity
- What is being tested?
- Panadol® and SafeTynadol®
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteTaiwan
- Study dates
- 19 May 2022to 31 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normal healthy adult subjects between 20-50 years of age.
- Body weight within 80-120% of ideal body weight. Male: Ideal body weight = (height - 80) * 0.7 Female: Ideal body weight = (height - 70) * 0.6
- Acceptable medical history and physical examination including:
- normal ECG results within six months prior to Period I (or Period III or Period V) dosing.
- no particular clinical significance in general disease history within two months prior to Period I (or Period III or Period V) dosing.
- Acceptable clinical laboratory determinations without significant deviation from normal values within two months prior to Period I (or Period III or Period V) dosing, which includes AST (SGOT), ALT (SGPT), r-GT, alkaline phosphatase, total bilirubin, albumin, glucose, BUN, uric acid, creatinine, total cholesterol, triglyceride (TG) and oral galactose single point (OGSP).
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- Acceptable hematology within two months prior to the study, which includes hemoglobin, hematocrit, red blood cells, MCV, MCH, MCHC, white blood cells, differential white blood cells and platelets.
- Acceptable urinalysis within two months prior to the study, which includes pH, blood, glucose and protein.
- Signed the written informed consent to participate in this study.
Who cannot join
- History or presence of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (the equivalent of 14 glasses of 120-mL wine or 14 cans of 350-mL beer), or other substance abuse within the prior two years.
- A clinically significant disorder involving the allergy, cardiovascular, respiratory, renal, gastrointestinal/hepatic, immunologic, hematologic, endocrine or neurologic system(s) or psychiatric disease (as determined by the clinical investigator).
- History of allergic response(s) to acetaminophen, mannitol, sucralose or related drugs.
- History of clinically significant allergies including drug allergies or allergic bronchial asthma.
- Evidence of chronic or acute infectious diseases.
- Any clinically significant illness or surgery during the one month prior to Period I (or Period III or Period V) dosing (as determined by the clinical investigator).
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- Taking any drug known to induce or inhibit hepatic drug metabolism within one month prior to the beginning of the study.
- Receiving any investigational drug within one month prior to Period I (or Period III or Period V) dosing.
- Taking any prescription medication or any nonprescription medication within two weeks prior to Period I (or Period III or Period V) doing.
- Donating greater than 150 ml of blood within two months prior to Period I (or Period III or Period V) dosing or donating plasma (e.g. plasmapheresis) within two weeks prior to Period I (or Period III or Period V) dosing.
- Consumption of caffeine, xanthine-containing products (i.e. coffee, tea, caffeine-containing sodas, colas and chocolate, etc.) and/or alcohol within 48 hours prior to days on which dosing is scheduled and during the periods when blood samples are being collected.
- Any other medical reason as determined by the clinical investigator.
- Subject is pregnant or breastfeeding.
- Women of childbearing potential disagree to use an acceptable method of contraception (e.g., hormonal contraceptives, IUD, barrier device or abstinence) throughout the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Single-blind, Parallel Group and Multiple - Dose Design Study to Evaluate the Pharmacokinetics of Acetaminophen and Its Toxic Metabolites With Panadol® and Various Formulations of SafeTynadol® in Healthy Volunteers
To investigate and compare the possible response of Panadol® and SafeTynadol® formulations in healthy volunteers.
Read the detailed description
Acetaminophen (AAP) is the most popular used analgesic/ antipyretic drug with serious hepatotoxic adverse effects; suicidal or unintentional overdose of AAP-induced hepatotoxicity. Cytochrome P450 2E1 (CYP2E1) is thought contribute to the responsible reactive metabolite N-acetyl-p-benzoquinone (NAPQI) of AAP overdose-induced hepatotoxicity. Pharmaceutical excipients are inactive ingredients that are added to a pharmaceutical compound. The objective of this study was to investigate the possible response of Panadol® (AAP alone) and SafeTynadol® (AAP with various selected excipients combination) formulations, while observing the AAP toxic metabolites (AAP-Cys) circumstances change in healthy volunteers. According to the current safety data, could be potentially develop hepatotoxicity-free AAP new formulation drug.
- Conditions
- Acetaminophen Toxicity
- Being tested
- Panadol®, SafeTynadol®
- Keywords
- acetaminophen, acute liver failure
- Medical subject headings
- Liver Failure, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Panadol®Drug
Also called Acetaminophen
Acetaminophen 500mg Tablet
SafeTynadol®Drug
Also called SNP-810
Acetaminophen 500mg Tablet
| Study group | Role | What they receive |
|---|---|---|
| Reference drug (1000mg) | Placebo comparator | Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period I and II. The study was completed when there were at least 12 evaluable subjects.
Panadol® oral dosage form (500 mg*2 tablets = 1000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study period. Receives: Drug: Panadol® |
| Test drug (1000mg) | Experimental | Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period I and II. The study was completed when there were at least 12 evaluable subjects.
SafeTynadol® oral dosage form (500 mg*2 tablets = 1000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study period. Receives: Drug: SafeTynadol® |
| Reference drug (4000mg) | Placebo comparator | Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period III and IV. The study was completed when there were at least 12 evaluable subjects.
Panadol® oral dosage form (500 mg*8 tablets = 4000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study period. Receives: Drug: Panadol® |
| Test drug (4000mg) | Experimental | Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period III and IV. The study was completed when there were at least 12 evaluable subjects.
SafeTynadol® oral dosage form (500 mg*8 tablets = 4000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study Receives: Drug: SafeTynadol® |
| Reference drug 2 tablets Q6H (28,000mg) | Placebo comparator | Eligible subjects were randomly assigned to either of the two treatment stage.Each treatment will be completed when there are at least 7 evaluable subjects. The evaluable subjects are randomized into period V.
Panadol® oral dosage form (500mg*2 tablets =1000mg) will be orally administered with 240 ml of water every 6 hours daily in each of the multiple-dose study period (Q6H, total 28 dosages, 56 tablets). Receives: Drug: Panadol® |
| Test drug 2 tablets Q6H (28,000mg) | Experimental | Eligible subjects were randomly assigned to either of the two treatment stage.Each treatment will be completed when there are at least 7 evaluable subjects. The evaluable subjects are randomized into period V.
SafeTynadol® oral dosage form (500mg*2 tablets =1000mg) will be orally administered with 240 ml of water every 6 hours daily in each of the multiple-dose study period (Q6H, total 28 dosages, 56 tablets). Receives: Drug: SafeTynadol® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage change from baseline of ALT peak level within study periods
ALT peak level in blood after administration
Measured: Blood samples were collected on days 2-7 (before dosing)
Secondary outcomes (9)
- Incidence of peak ALT elevations > 1X ULN within study periods;
The blood concentration of ALT.
Measured: Day 1-7
- Incidence of peak ALT elevations > 2X ULN within study periods;
The blood concentration of ALT.
Measured: Day 1-7
- Incidence of peak ALT elevations > 3X ULN within study periods;
The blood concentration of ALT.
Measured: Day 1-7
- Incidence of peak ALT elevations > 5X ULN within study periods;
The blood concentration of ALT.
Measured: Day 1-7
- Incidence of peak ALT elevations > 8X ULN within study periods;
The blood concentration of ALT.
Measured: Day 1-7
- Incidence of total bilirubin ≥ 2.5mg/dL within study periods;
The blood concentration of total bilirubin.
Measured: Day 1-7
- Hepatic failure rate (hepatic encephalopathy, ascites, total bilirubin ≥ 2.5mg/dL or liver transplantation) within study periods;
The blood concentration of hepatic encephalopathy, ascites, total bilirubin.
Measured: Day 1-7
- The time-interval weighted area under the curve (AUC) of free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts within study periods.
The blood concentration of free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts
Measured: Day 1-7
- The time-interval weighted area under the curve (AUC) of ALT level within study periods
The blood concentration of ALT.
Measured: Day 1-7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2018
- Study start19 May 2022
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acetaminophen ToxicityStudies 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single Blindie
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sinew Pharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- TeYu Mr Lin, Dr., Principal investigator, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03451487
- Sponsor's protocol ID
- Oral AAP-001
- Status last verified
- Apr 2023
- First submitted
- 24 Feb 2018
- Last updated
- 18 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Single-blind, Parallel Group and Multiple - Dose Design Study to Evaluate the Pharmacokinetics of Acetaminophen and Its Toxic Metabolites With Panadol® and Various Formulations of SafeTynadol® in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03451487
- Acronym / sponsor ID
- Oral AAP-001
- Conditions
- Acetaminophen Toxicity
- Keywords
- acetaminophen, acute liver failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Sinew Pharma Inc.Industry (pharma, biotech, devices)
- Study start
- 19 May 2022 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 1 Mar 2018 (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 investigate and compare the possible response of Panadol® and SafeTynadol® formulations in healthy volunteers.
Detailed description
Acetaminophen (AAP) is the most popular used analgesic/ antipyretic drug with serious hepatotoxic adverse effects; suicidal or unintentional overdose of AAP-induced hepatotoxicity. Cytochrome P450 2E1 (CYP2E1) is thought contribute to the responsible reactive metabolite N-acetyl-p-benzoquinone (NAPQI) of AAP overdose-induced hepatotoxicity. Pharmaceutical excipients are inactive ingredients that are added to a pharmaceutical compound. The objective of this study was to investigate the possible response of Panadol® (AAP alone) and SafeTynadol® (AAP with various selected excipients combination) formulations, while observing the AAP toxic metabolites (AAP-Cys) circumstances change in healthy volunteers. According to the current safety data, could be potentially develop hepatotoxicity-free AAP new formulation drug.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 6
- Model description
- Single Blindie
| Arm | Type | Receives |
|---|---|---|
| Reference drug (1000mg) | Placebo comparator | Drug: Panadol®Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period I and II. The study was completed when there were at least 12 evaluable subjects. Panadol® oral dosage form (500 mg*2 tablets = 1000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study period. |
| Test drug (1000mg) | Experimental | Drug: SafeTynadol®Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period I and II. The study was completed when there were at least 12 evaluable subjects. SafeTynadol® oral dosage form (500 mg*2 tablets = 1000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study period. |
| Reference drug (4000mg) | Placebo comparator | Drug: Panadol®Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period III and IV. The study was completed when there were at least 12 evaluable subjects. Panadol® oral dosage form (500 mg*8 tablets = 4000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study period. |
| Test drug (4000mg) | Experimental | Drug: SafeTynadol®Eligible subjects were randomly assigned to either of the two treatment sequence.The evaluable subjects were those who had completed both period III and IV. The study was completed when there were at least 12 evaluable subjects. SafeTynadol® oral dosage form (500 mg*8 tablets = 4000 mg) was orally administered with 240 ml of water once daily in the morning in each of the single-dose study |
| Reference drug 2 tablets Q6H (28,000mg) | Placebo comparator | Drug: Panadol®Eligible subjects were randomly assigned to either of the two treatment stage.Each treatment will be completed when there are at least 7 evaluable subjects. The evaluable subjects are randomized into period V. Panadol® oral dosage form (500mg*2 tablets =1000mg) will be orally administered with 240 ml of water every 6 hours daily in each of the multiple-dose study period (Q6H, total 28 dosages, 56 tablets). |
| Test drug 2 tablets Q6H (28,000mg) | Experimental | Drug: SafeTynadol®Eligible subjects were randomly assigned to either of the two treatment stage.Each treatment will be completed when there are at least 7 evaluable subjects. The evaluable subjects are randomized into period V. SafeTynadol® oral dosage form (500mg*2 tablets =1000mg) will be orally administered with 240 ml of water every 6 hours daily in each of the multiple-dose study period (Q6H, total 28 dosages, 56 tablets). |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Normal healthy adult subjects between 20-50 years of age.
- Body weight within 80-120% of ideal body weight. Male: Ideal body weight = (height - 80) * 0.7 Female: Ideal body weight = (height - 70) * 0.6
- Acceptable medical history and physical examination including:
- Acceptable clinical laboratory determinations without significant deviation from normal values within two months prior to Period I (or Period III or Period V) dosing, which includes AST (SGOT), ALT (SGPT), r-GT, alkaline phosphatase, total bilirubin, albumin, glucose, BUN, uric acid, creatinine, total cholesterol, triglyceride (TG) and oral galactose single point (OGSP).
- Acceptable hematology within two months prior to the study, which includes hemoglobin, hematocrit, red blood cells, MCV, MCH, MCHC, white blood cells, differential white blood cells and platelets.
Key exclusion criteria (14 listed)
- History or presence of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (the equivalent of 14 glasses of 120-mL wine or 14 cans of 350-mL beer), or other substance abuse within the prior two years.
- A clinically significant disorder involving the allergy, cardiovascular, respiratory, renal, gastrointestinal/hepatic, immunologic, hematologic, endocrine or neurologic system(s) or psychiatric disease (as determined by the clinical investigator).
- History of allergic response(s) to acetaminophen, mannitol, sucralose or related drugs.
- History of clinically significant allergies including drug allergies or allergic bronchial asthma.
- Evidence of chronic or acute infectious diseases.
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 |
|---|---|---|
| Panadol®Also: AcetaminophenAcetaminophen 500mg Tablet | Drug | Reference drug (1000mg), Reference drug (4000mg), Reference drug 2 tablets Q6H (28,000mg) |
| SafeTynadol®Also: SNP-810Acetaminophen 500mg Tablet | Drug | Test drug (1000mg), Test drug (4000mg), Test drug 2 tablets Q6H (28,000mg) |
Primary outcome
Percentage change from baseline of ALT peak level within study periods
Time frame: Blood samples were collected on days 2-7 (before dosing)
ALT peak level in blood after administration
9 secondary outcomes
- Incidence of peak ALT elevations > 1X ULN within study periods;
Time frame: Day 1-7
- Incidence of peak ALT elevations > 2X ULN within study periods;
Time frame: Day 1-7
- Incidence of peak ALT elevations > 3X ULN within study periods;
Time frame: Day 1-7
- Incidence of peak ALT elevations > 5X ULN within study periods;
Time frame: Day 1-7
- Incidence of peak ALT elevations > 8X ULN within study periods;
Time frame: Day 1-7
- Incidence of total bilirubin ≥ 2.5mg/dL within study periods;
Time frame: Day 1-7
- Hepatic failure rate (hepatic encephalopathy, ascites, total bilirubin ≥ 2.5mg/dL or liver transplantation) within study periods;
Time frame: Day 1-7
- The time-interval weighted area under the curve (AUC) of free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts within study periods.
Time frame: Day 1-7
- The time-interval weighted area under the curve (AUC) of ALT level within study periods
Time frame: Day 1-7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2023.
Related trials for Acetaminophen Toxicity
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. This study is not recruiting at the moment.
TeYu Mr Lin, Dr. principal investigator
Principal Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Panadol® and SafeTynadol® in people with Acetaminophen Toxicity, 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 9 inclusion and 14 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: finished, as of the sponsor's last update on 18 Jul 2023. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage change from baseline of ALT peak level within study periods (time frame: Blood samples were collected on days 2-7 (before dosing)). 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 18 Jul 2023.