A Randomized, Single-blind, Parallel Group and Multiple - Dose Design Study

July 17, 2023 updated by: Sinew Pharma Inc.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

28

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Neihu District
      • Taipei, Neihu District, Taiwan, 114202
        • Tri-Service General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Normal healthy adult subjects between 20-50 years of age.
  2. 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
  3. 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.
  4. 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).
  5. 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.
  6. Acceptable urinalysis within two months prior to the study, which includes pH, blood, glucose and protein.
  7. Signed the written informed consent to participate in this study.

Exclusion Criteria:

  1. 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.
  2. 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).
  3. History of allergic response(s) to acetaminophen, mannitol, sucralose or related drugs.
  4. History of clinically significant allergies including drug allergies or allergic bronchial asthma.
  5. Evidence of chronic or acute infectious diseases.
  6. 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).
  7. Taking any drug known to induce or inhibit hepatic drug metabolism within one month prior to the beginning of the study.
  8. Receiving any investigational drug within one month prior to Period I (or Period III or Period V) dosing.
  9. Taking any prescription medication or any nonprescription medication within two weeks prior to Period I (or Period III or Period V) doing.
  10. 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.
  11. 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.
  12. Any other medical reason as determined by the clinical investigator.
  13. Subject is pregnant or breastfeeding.
  14. 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / 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:
  • Acetaminophen
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:
  • SNP-810
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:
  • Acetaminophen
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:
  • SNP-810
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:
  • Acetaminophen
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:
  • SNP-810

What is the study measuring?

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

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

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

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: TeYu Mr Lin, Dr., Principal Investigator

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2022

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

February 24, 2018

First Submitted That Met QC Criteria

February 28, 2018

First Posted (Actual)

March 1, 2018

Study Record Updates

Last Update Posted (Actual)

July 18, 2023

Last Update Submitted That Met QC Criteria

July 17, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • Oral AAP-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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