A Randomized, Single-blind, Parallel Group and Multiple - Dose Design Study
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
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Not Applicable
Contacts and Locations
Study Contact
Study Contact
- Name: WanLing Ms Yang, Research
- Phone Number: +886-2-2788-5365
- Email: wlyang@sinewpharma.com
Study Contact Backup
- Name: TungYuan Mr Shih, Director
- Phone Number: +886-2-2788-5365
- Email: tyshih@sinewpharma.com
Study Locations
-
-
Neihu District
-
Taipei, Neihu District, Taiwan, 114202
- Tri-Service General Hospital
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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).
- 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.
Exclusion Criteria:
- 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).
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Placebo Comparator: Reference drug (1000mg)
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. |
Acetaminophen 500mg Tablet
Other Names:
|
|
Experimental: Test drug (1000mg)
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. |
Acetaminophen 500mg Tablet
Other Names:
|
|
Placebo Comparator: Reference drug (4000mg)
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. |
Acetaminophen 500mg Tablet
Other Names:
|
|
Experimental: Test drug (4000mg)
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 |
Acetaminophen 500mg Tablet
Other Names:
|
|
Placebo Comparator: Reference drug 2 tablets Q6H (28,000mg)
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). |
Acetaminophen 500mg Tablet
Other Names:
|
|
Experimental: Test drug 2 tablets Q6H (28,000mg)
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). |
Acetaminophen 500mg Tablet
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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
|
Blood samples were collected on days 2-7 (before dosing)
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
- Incidence of peak ALT elevations > 1X ULN within study periods;
Time Frame: Day 1-7
|
The blood concentration of ALT.
|
Day 1-7
|
|
- Incidence of peak ALT elevations > 2X ULN within study periods;
Time Frame: Day 1-7
|
The blood concentration of ALT.
|
Day 1-7
|
|
- Incidence of peak ALT elevations > 3X ULN within study periods;
Time Frame: Day 1-7
|
The blood concentration of ALT.
|
Day 1-7
|
|
- Incidence of peak ALT elevations > 5X ULN within study periods;
Time Frame: Day 1-7
|
The blood concentration of ALT.
|
Day 1-7
|
|
- Incidence of peak ALT elevations > 8X ULN within study periods;
Time Frame: Day 1-7
|
The blood concentration of ALT.
|
Day 1-7
|
|
- Incidence of total bilirubin ≥ 2.5mg/dL within study periods;
Time Frame: Day 1-7
|
The blood concentration of total bilirubin.
|
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 blood concentration of hepatic encephalopathy, ascites, total bilirubin.
|
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 blood concentration of free plasma acetaminophen-cysteine (AAP-Cys) and AAP-Cys adducts
|
Day 1-7
|
|
- The time-interval weighted area under the curve (AUC) of ALT level within study periods
Time Frame: Day 1-7
|
The blood concentration of ALT.
|
Day 1-7
|
Other Outcome Measures
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
- Incidence of adverse events
Time Frame: Day 1-12
|
Safety
|
Day 1-12
|
|
- Clinical laboratory test
Time Frame: Day 1-12
|
Concentrations of acetaminophen in plasma
|
Day 1-12
|
|
- Clinical laboratory test
Time Frame: Day 1-12
|
Concentrations of acetaminophen metabolites (AAP-Glc) in plasma
|
Day 1-12
|
|
- Clinical laboratory test
Time Frame: Day 1-12
|
Concentrations of acetaminophen metabolites (AAP-Sul) in plasma
|
Day 1-12
|
|
- Clinical laboratory test
Time Frame: Day 1-12
|
Concentrations of acetaminophen metabolites (GS-AAP) in plasma
|
Day 1-12
|
|
- Clinical laboratory test
Time Frame: Day 1-12
|
Concentrations of acetaminophen metabolites (AAP-Cys) in plasma
|
Day 1-12
|
|
- Clinical laboratory test
Time Frame: Day 1-12
|
Concentrations of acetaminophen metabolites (AAP-NAC) in plasma
|
Day 1-12
|
|
- Vital sign
Time Frame: Day 1-12
|
Heart rate (bpm)
|
Day 1-12
|
|
- Vital sign
Time Frame: Day 1-12
|
Blood pressure (mmHg)
|
Day 1-12
|
|
- Vital sign
Time Frame: Day 1-12
|
Temperature (℃)
|
Day 1-12
|
Collaborators and Investigators
Sponsor
Sponsor
Investigators
Investigators
- Principal Investigator: TeYu Mr Lin, Dr., Principal Investigator
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- Oral AAP-001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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