Bioequivalence Study of Paracetamol With Oral Single Dose Administration in Healthy Adult Subjects Under Fasting Conditions

NCT06855576 | Completed Phase 1

• 2 other identifiers: 3001412024-514198-23-00
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the bioequivalence of new formulated orodispersible tablet (ODT) containing 500 milligram (mg) paracetamol in comparison to the European marketed Alvedon (paracetamol) 500 mg film-coated tablets and the Australian marketed Panadol (paracetamol) 500 mg film-coated tablets as reference products.

Conditions

Fever; Pain

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Concentration (Cmax) for Paracetamol ODT (Test) Versus (Vs) Paracetamol (Alvedon Film-coated Tablet) (Reference 1)

  Cmax is defined as maximum observed post-dose plasma concentration for paracetamol. Blood samples will be collected at indicated timepoints for the analysis of Cmax. Pharmacokinetic (PK) parameters will be determined by non-compartmental analysis.

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• Area Under the Concentration Versus Time Curve from Dosing Time to the Last Measurement Time Point (AUC0-tlast) for Paracetamol ODT (Test) Vs Paracetamol (Alvedon Film-coated Tablet) (Reference 1)

  AUC0-tlast is defined as area under the concentration Vs time curve from dosing time to the last measurement time point with a concentration value above the lower limit of quantitation, calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations). Blood samples will be collected at indicated timepoints for the analysis of AUC0-tlast. PK parameters will be determined by non-compartmental analysis.

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• Time to Reach Maximum Concentration (tmax) for Paracetamol ODT (Test) Vs Paracetamol (Alvedon Film-coated Tablet) (Reference 1)

  Blood samples will be collected at indicated timepoints for the analysis of tmax. PK parameters will be determined by non-compartmental analysis.

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• Cmax for Paracetamol ODT (Test) Vs Paracetamol (Pandol Film-coated Tablet) (Reference 2)

  Cmax is defined as maximum observed post-dose plasma concentration for paracetamol. Blood samples will be collected at indicated timepoints for the analysis of Cmax. PK parameters will be determined by non-compartmental analysis.

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• AUC0-tlast for Paracetamol ODT (Test) Vs Paracetamol (Pandol Film-coated Tablet) (Reference 2)

  AUC0-tlast is defined as area under the concentration Vs time curve from dosing time to the last measurement time point with a concentration value above the lower limit of quantitation, calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations. Blood samples will be collected at indicated timepoints for the analysis of AUC0-tlast). PK parameters will be determined by non-compartmental analysis.

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• tmax for Paracetamol ODT (Test) Vs Paracetamol (Pandol Film-coated Tablet) (Reference 2)

  Blood samples will be collected at indicated timepoints for the analysis of tmax. PK parameters will be determined by non-compartmental analysis.

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

Secondary Outcomes (12)

• Area Under the Plasma Concentration Versus Time Curve Calculated From Time Zero to Infinity [AUC (0-inf)] for Paracetamol ODT (Test)

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• AUC (0-inf) for Paracetamol (Alvedon Film-coated Tablet) (Reference 1)

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• AUC (0-inf) for Paracetamol (Pandol Film-coated Tablet) (Reference 2)

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• AUCexpol% for Paracetamol ODT (Test)

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

• AUCexpol% for Paracetamol (Alvedon Film-coated Tablet) (Reference 1)

  Within one hour prior to dosing, at 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 90, 120, 150, 180 minutes and at 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours following dosing in each treatment period

Study Arms (3)

Test Product

EXPERIMENTAL

Participants will be randomly assigned as per cross-over design to receive oral administration of one paracetamol ODT (test product) on day 1 of period 1, one Alvedon film-coated tablet (reference product 1) on day 1 of period 2 and one Panadol film-coated tablet (reference product 2) on day 1 of period 3, each under fasting conditions. There will be at least 72 hours of washout between each period (no more than 7 days).

Drug: Paracetamol ODT; Drug: Alvedon film-coated tablet; Drug: Panadol film-coated Tablet

Reference Product 1

ACTIVE COMPARATOR

Participants will be randomly assigned as per cross-over design to receive oral administration of one Alvedon film-coated tablet (reference product 1) on day 1 of period 1, one Panadol film-coated tablet (reference product 2) on day 1 of period 2 and one paracetamol ODT (test product) on day 1 of period 3, each under fasting conditions. There will be at least 72 hours of washout between each period (no more than 7 days).

Drug: Paracetamol ODT; Drug: Alvedon film-coated tablet; Drug: Panadol film-coated Tablet

Reference Product 2

ACTIVE COMPARATOR

Participants will be randomly assigned as per cross-over design to receive oral administration of one Panadol film-coated tablet (reference product 2) on day 1 of period 1, and one paracetamol ODT (test product) on day 1 of period 2 and one Alvedon film-coated tablet (reference product 1) on day 1 of period 3, each under fasting conditions. There will be at least 72 hours of washout between each period (no more than 7 days).

Drug: Paracetamol ODT; Drug: Alvedon film-coated tablet; Drug: Panadol film-coated Tablet

Interventions

Paracetamol ODT DRUG

Experimental Paracetamol 500 mg ODT

Reference Product 1; Reference Product 2; Test Product

Alvedon film-coated tablet DRUG

Marketed Paracetamol 500 mg film-coated tablet

Reference Product 1; Reference Product 2; Test Product

Panadol film-coated Tablet DRUG

Marketed Paracetamol 500 mg film-coated tablet

Reference Product 1; Reference Product 2; Test Product

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the participants participating in the clinical trial.
• Sex: male/female.
• Age: 18 to 55 years (including)
• Body-mass index (BMI): more than or equal to (\>=)18.5 kilogram per meter square (kg/m\^2) and less than or equal to (\<=) 30.0 kg/m\^2.
• Body weight: \>= 50.0 kg for males and \>= 45.0 kg for females.
• Good state of health.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Female participant of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 7 days after the last dose of assigned treatment.
• Non-smoker or ex-smoker for at least 3 months (including non-nicotine vapers, nicotine chewing gum or pouches or nicotine replacement therapy).

You may not qualify if:

• Safety Concerns
• Existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient.
• Existing renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient.
• Current evidence of ongoing hepatic disease or impaired hepatic function at screening. A participant will be excluded if more than one of the following lab value deviations are found: 1) Aspartate aminotransferase (AST) (\>= 1.2 upper limit of normal \[ULN\]), Alanine transaminase (ALT) (\>= 1.2 ULN), 2) Gamma-glutamyl transferase (GGT) (\>= 1.2 ULN), Alkaline phosphatase (ALP) (\>= 1.2 ULN), 3) total bilirubin (greater than \[\>\] 2.00 milligrams per deciliter (mg/dL), except in case of existing Morbus Gilbert-Meulengracht deduced from anamnesis/medical history) or creatine kinase (\>= 3 ULN), and creatinine \> 0.1 mg/dL ULN (limit of \> 0.1 mg/dL correspondents to of \> 9 micromole per liter \[μmol/l\] ULN). A single deviation from the above values is acceptable and will not exclude the candidate, unless specifically advised by the investigator.
• Existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient.
• History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders.
• History or clinical evidence at screening of pancreatic injury or pancreatitis.
• History of inflammatory bowel disease or gastrointestinal bleeding including peptic ulcers.
• Diagnosis of systemic lupus erythematosus, thyroid diseases, secondary Raynaud's syndrome; known hyperkalemia.
• Evidence of urinary obstruction (example, due to benign prostate hyperplasia) or difficulty in voiding at screening.
• Status of glutathione depletion (eating disorder, cystic fibrosis, human immunodeficiency virus \[HIV\] infection, starvation, cachexia) due to metabolic deficiencies.
• Oral surgery within 4 weeks of dosing, dental work or extractions within 2 weeks of dosing, or presence of any clinically significant (as determined by the principal investigator or designee) oral pathology including lesions, sores or inflammation.
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling or gastric banding (note: this is not applicable for minor abdominal surgery without significant tissue resection, example, appendectomy and herniorrhaphy).
• Participants, who report a frequent occurrence of migraine attacks.
• Acute or chronic diseases which may interfere with the pharmacokinetics of the investigational medicinal product (IMP).

Sponsors & Collaborators

• HALEON: lead

Study Sites (1)

SocraTec R&D GmbH

Erfurt, Thuringia, 99084, Germany

Location

MeSH Terms

Conditions

Fever; Pain

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 4, 2025
• Study Start: March 5, 2025
• Primary Completion: April 17, 2025
• Study Completion: April 17, 2025
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension can be granted, when justified, for up to another 12 months.

Locations

DE (1)