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A Study to Evaluate the Pharmacokinetics of Acetaminophen and Its Toxic Metabolites With 2 Formulations (Panadol and SafeTynadol) in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03451487
Recruitment Status : Completed
First Posted : March 1, 2018
Last Update Posted : March 1, 2018
Sponsor:
Information provided by (Responsible Party):
Sinew Pharma Inc.

Tracking Information
First Submitted Date  ICMJE February 24, 2018
First Posted Date  ICMJE March 1, 2018
Last Update Posted Date March 1, 2018
Actual Study Start Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2018)
Blood concentration of SafeTynadol [ Time Frame: PK samples were collected at pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post dose (a total of 13 samples per subject in each period). ]
Concentrations of acetaminophen and it metabolites (AAP-Glc、AAP-Sul、GS-Catechol、GS-AAP、AAP-Cys、AAP-NAC) in plasma will be measured by a specific and sensitive LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of AAP and its metabolites in health subjects oral Panadol® (AAP alone) and SafeTynadol (AAP with various selected excipients combinations) to assess the safety information. The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Pharmacokinetics of Acetaminophen and Its Toxic Metabolites With 2 Formulations (Panadol and SafeTynadol) in Healthy Volunteers
Official Title  ICMJE A Randomized, Open-label, Single Dose, Crossover Design Phase I Study to Evaluate the Pharmacokinetics of Acetaminophen and Its Toxic Metabolites With 2 Formulations (Panadol and SafeTynadol) in Healthy Volunteers
Brief Summary 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Acetaminophen Toxicity
Intervention  ICMJE
  • Drug: Panadol®
    Acetaminophen 500mg Tablet
    Other Name: Acetaminophen
  • Drug: SafeTynadol®
    Acetaminophen 500mg Tablet
    Other Name: SNP-810
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Panadol®
  • 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.

    Intervention: Drug: SafeTynadol®
  • 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.

    Intervention: Drug: Panadol®
  • 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

    Intervention: Drug: SafeTynadol®
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 28, 2018)
26
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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) x 0.7 Female: Ideal body weight = (height - 70) x 0.6
  3. Acceptable medical history and physical examination including:

    • normal ECG results within six months prior to Period I dosing.
    • no particular clinical significance in general disease history within two months prior to Period I dosing.
  4. Acceptable clinical laboratory determinations without significant deviation from normal values within two months prior to Period I dosing, which includes AST (SGOT), ALT (SGPT), g-GT, alkaline phosphatase, total bilirubin, albumin, glucose, BUN, uric acid, creatinine, total cholesterol, triglyceride (TG) and galactose single point (GSP).
  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. Recent history of drug or alcohol addiction or abuse within the past year.
  2. A clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, 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 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 dosing.
  9. Taking any prescription medication or any nonprescription medication within two weeks prior to Period I dosing.
  10. Donating greater than 150 ml of blood within two months prior to Period I dosing or donating plasma (e.g. plasmapheresis) within two weeks prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study.
  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.

Note: Sponsor clarified the terms "prior to Period I dosing" described in inclusion criteria and exclusion criteria meant "prior to Period III dosing" in high dose stage.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03451487
Other Study ID Numbers  ICMJE TSGHIRB No.2-104-01-011
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sinew Pharma Inc.
Study Sponsor  ICMJE Sinew Pharma Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sinew Pharma Inc.
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP