A Partial Randomized, Single-blind or Open-label, Dose-escalation With Multiple-dose Design Study to Evaluate the Pharmacokinetics of Acetaminophen and Its Toxic Metabolites With Panadol® and SafeTynadol® in Healthy Volunteers

NCT05563961 | Recruiting

• 1 other identifier: Oral AAP-002
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate and compare the possible response of Panadol® and SafeTynadol® formulations in healthy volunteers and the safety in SafeTynadol® dose-limiting hepatotoxicity.

Conditions

Hepatitis; Pharmacology

Keywords

acetaminophen; acute liver failure

Outcome Measures

Primary Outcomes (1)

• ALT level within study periods

  Day 1-9

Secondary Outcomes (10)

• Incidence of peak ALT elevations > 1X ULN within study periods

  Day 1-9

• Incidence of peak ALT elevations > 2X ULN within study periods

  Day 1-9

• Incidence of peak ALT elevations > 3X ULN within study periods

  Day 1-9

• Incidence of peak ALT elevations > 5X ULN within study periods

  Day 1-9

• Incidence of peak ALT elevations > 8X ULN within study periods

  Day 1-9

Study Arms (2)

Panadol

ACTIVE COMPARATOR

• Cohort 1- 6 Subjects to receive oral Panadol® 4,000 mg (2 tablets Q6H, 4 dosages, 8 tablets or 4,000 mg)

Drug: Panadol®

SafeTynadol®

EXPERIMENTAL

* Cohort 2- 6 Subjects to receive oral SafeTynadol® 4,000 mg (2 tablets Q6H, 4 dosages, 8 tablets or 4,000 mg) * Cohort 3- 6 Subjects to receive oral SafeTynadol® 4,500 mg (3 tablets at first dosage and 2 tablets at second to forth dosage Q6H, 4 dosages, 9 tablets or 4,500 mg) * Cohort 4- 6 Subjects to receive oral SafeTynadol® 5,000 mg (3 tablets at first to second dosage and 2 tablets at third to forth dosage Q6H, 4 dosages, 10 tablets or 5,000 mg) * Cohort 5- 6 Subjects to receive oral SafeTynadol® 6,000 mg (3 tablets Q6H, 4 dosages, 12 tablets or 6,000 mg) * Cohort 6- 6 Subjects to receive oral SafeTynadol® 8,000 mg (4 tablets Q6H, 4 dosages, 16 tablets or 8,000 mg) * Cohort 7- 6 Subjects to receive oral SafeTynadol® 10,000 mg (5 tablets Q6H, 4 dosages, 20 tablets or 10,000 mg) * Cohort 8- 6 Subjects to receive oral SafeTynadol® 12,000 mg (6 tablets Q6H, 4 dosages, 24 tablets or 12,000 mg)

Drug: SafeTynadol®

Interventions

Panadol® DRUG

Reference Drug. Multiple-dose stage: Cohort 1, 2 tablets Q6H (total 4 dosages, 8 tablets or 4,000 mg)

Panadol

SafeTynadol® DRUG

Test Drugs. Multiple-dose stage: Cohort 2, 2 tablets Q6H (total 4 dosages, 8 tablets or 4,000 mg) Cohort 3, 3 tablets at first dosage and 2 tablets at second to forth dosage Q6H (total 4 dosages, 9 tablets or 4,500 mg) Cohort 4, 3 tablets at first to second dosage and 2 tablets at third to forth dosage Q6H (total 4 dosages, 10 tablets or 5,000 mg) Cohort 5, 3 tablets Q6H (total 4 dosages, 12 tablets or 6,000 mg) Cohort 6, 4 tablets Q6H (total 4 dosages, 16 tablets or 8,000 mg) Cohort 7, 5 tablets Q6H (total 4 dosages, 20 tablets or 10,000 mg) Cohort 8, 6 tablets Q6H (total 4 dosages, 24 tablets or 12,000 mg)

SafeTynadol®

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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) x 0.7
• Female Ideal body weight = (height - 70) x 0.6
• Acceptable medical history and physical examination including:
• normal ECG results within six months prior to dosing.
• no particular clinical significance in general disease history within two months prior to dosing.
• Acceptable clinical laboratory determinations without significant deviation from normal values within two months prior to dosing, which includes AST (SGOT), ALT (SGPT), r-GT, alkaline phosphatase, total bilirubin, albumin, glucose, BUN, uric acid, creatinine, total cholesterol, triglyceride (TG), PT(INR) and OGSP.
• Acceptable hematology within two months prior to dosing, 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 dosing, which includes pH, blood, glucose and protein.
• Signed the written informed consent to participate in this study

You may not qualify if:

• 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 two month prior to 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 dosing.
• Taking any prescription medication or any nonprescription medication within two weeks prior to dosing.
• Donating greater than 150 ml of blood within two months prior to dosing or donating plasma (e.g. plasmapheresis) within two weeks prior to 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, intrauterine device (IUD), barrier device or abstinence) throughout the study.

Sponsors & Collaborators

• Sinew Pharma Inc.: lead

Study Sites (1)

Tri-Service General Hospital

Taipei, Neihu District, 114202, Taiwan

RECRUITING

MeSH Terms

Conditions

Hepatitis; Liver Failure, Acute

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Liver Failure; Hepatic Insufficiency

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Central Study Contacts

ChengHuei Mr. Hsiong, Vice President

CONTACT

+886-2-2788-5365; info@sinewpharma.com

PoKuan Mr. Chao, Research

CONTACT

+886-2-2788-5365; paikuan.chao@sinewpharma.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: October 3, 2022
• Study Start: October 28, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 27, 2024

Record last verified: 2024-02

Locations

TW (1)