Clinical trial NCT06855576: Bioequivalence Study of Paracetamol With Oral Single Dose Administration in Healthy Adult Subjects Under Fasting Conditions
Official title: A Phase I, Randomised, Open Label, Single Center, Single Oral Dose, Three Treatment, Three Period, Three Sequence, Change-over Bioequivalence Study of Paracetamol Orodispersible Tablet 500 mg (Haleon) to Assess Bioequivalence With Alvedon 500 mg Film-Coated Tablet (Haleon, Sweden) and Panadol 500 mg Film-Coated Tablet (Haleon, Australia) in Healthy Adult Subjects Under Fasting Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fever
Pain
Lead sponsor: HALEON
Sponsor class: INDUSTRY
First posted: 2025-03-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Detailed description: This will be a single center, open-label, randomized (order of treatments), balanced, 3-period, 3-sequence, single dose, change-over trial with oral administration under fasting conditions separated by a washout period of at least 72 hours. Fifty-four healthy participants of both sexes (27 male, 27 female) are intended to be randomized to obtain 42 evaluable participants. The investigational products will be administered in fasted state as single oral doses of 500 mg paracetamol tablet. 1 tablet of test and 1 film-coated tablet of reference 1 and 1 film-coated tablet of reference 2 will be administered in a cross-over manner. Blood sampling will be performed over 24-hour post dose in order to characterize pharmacokinetic parameters.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* Safety Concerns

  1. Existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient.
  2. Existing renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient.
  3. 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.
  4. Existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient.
  5. History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders.
  6. History or clinical evidence at screening of pancreatic injury or pancreatitis.
  7. History of inflammatory bowel disease or gastrointestinal bleeding including peptic ulcers.
  8. Diagnosis of systemic lupus erythematosus, thyroid diseases, secondary Raynaud's syndrome; known hyperkalemia.
  9. Evidence of urinary obstruction (example, due to benign prostate hyperplasia) or difficulty in voiding at screening.
  10. Status of glutathione depletion (eating disorder, cystic fibrosis, human immunodeficiency virus \[HIV\] infection, starvation, cachexia) due to metabolic deficiencies.
  11. 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.
  12. 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).
  13. Participants, who report a frequent occurrence of migraine attacks.
  14. Acute or chronic diseases which may interfere with the pharmacokinetics of the investigational medicinal product (IMP).
  15. Clinically relevant chronic or acute infectious illnesses or febrile infections within two weeks prior to start of the study.
  16. History or current evidence of renal disease or impaired renal function at screening as indicated by abnormal levels of serum creatinine (\> 1.43 mg/dL) or blood urea nitrogen (BUN) (\>= 35 mg/dL) or the presence of clinically significant abnormal urinary constituents (example, albuminuria).
  17. Systolic blood pressure less than (\<) 90 or \> 139 millimeter of mercury (mmHg).
  18. Diastolic blood pressure \< 50 or \> 89 mmHg.
  19. Heart rate \< 50 beats per minute (bpm) or \> 90 bpm.
  20. Corrected QT interval (QTc) interval \> 450 milliseconds (ms) for men and \> 470 ms for women.
  21. Hemoglobin value \< 12.0 grams per deciliter (g/dL) for males and \< 11.5 g/dL for females.
  22. Evidence or history of medication overuse headache, or allergic disease to medication within the last 5 years that may increase the risk associated with study participation.
  23. Laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator.
  24. Positive anti-HIV-test (if positive to be verified by western blot), hepatitis B surface antigen (HBs-AG) test and anti-hepatitis B core immunoglobulin M (HBc IgM) or anti-hepatitis C virus (HCV) test.
  25. Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations.
  26. Any history of asthma, urticaria, or other significant allergic diathesis or allergic reaction to any other pain reliever/fever reducer. Participant with uncomplicated seasonal allergic rhinitis can be accepted if expected allergy season is clearly outside enrollment/treatment period.
  27. History of severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator.
* Lack of suitability for the clinical trial

  1. History of illegal or legal drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana, codeine) within 1 month or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, any opioid derivatives such as heroin or fentanyl, and amphetamine derivatives) within 3 months prior to screening.
  2. Positive alcohol, cotinine or drug test at screening examination.
  3. History of alcohol abuse in the last 5 years or regular intake of alcoholic food or beverages of \>= 24 gram (g) pure ethanol for men or \>= 12 g pure ethanol for women per day.
  4. Participants who are on a diet which could affect the pharmacokinetics of the active ingredient.
  5. Regular intake of beverages or food containing xanthine derivatives or xanthine-related compounds (example, coffee, tea, caffeine-containing sodas and chocolate), equivalent to \>= 500 milligram (mg) xanthine per day.
  6. Performance of strenuous physical exercise (body building, high performance sports) from 2 weeks prior to admission and throughout the entire study.
  7. Participant reports consumption of any drug metabolizing enzyme (example, Cytochrome P450 3A4 (CYP3A4) or other cytochrome P450 enzymes) inducing or inhibiting aliments, beverages or food supplements (example, broccoli, Brussels sprouts, grapefruit, grapefruit juice, star fruit, St. John's Wort and so on) within 2 weeks prior to admission to the unit.
  8. Use of any systemic or topical medication (including over the counter \[OTC\] medications, herbal remedies, cannabidiol cosmetics and any anticholinergic medicines or other medicines that may cause dry mouth) within 2 weeks or within less than 10 times the elimination half-life of the respective drug (whichever is longer) before first scheduled study drug administration, or is anticipated to require any concomitant medication during that period or at any time throughout the study.
  9. Any history of long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.
  10. Any vaccination, including Coronavirus disease (COVID)-19 vaccine, within 14 days prior to the first dose.
  11. Donation of plasma within 7 days prior to dosing or donation or loss of 500 milliliter (mL) or more of whole blood within 8 weeks prior to dosing.
  12. Participation in a clinical trial in which they have tried an IMP, a medical device or a marketed medicinal product during the last 6 months prior to individual enrolment of the participant.
  13. Simultaneous participation in another clinical trial with active ingredients, medical devices or marketed medicinal products.
* For female participants with childbearing potential only

  1. Positive pregnancy test at screening examination.
  2. Pregnant or lactating women.
  3. Female participants who do not agree to apply highly effective contraceptive methods.
* Administrative reasons

  1. Close affiliation with the sponsor or the investigational site; example, a close relative of the investigator, dependent person (example, employee of or student at the investigational site), employee of the sponsor or affiliates.
  2. Participants who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) for Paracetamol ODT (Test) Versus (Vs) Paracetamol (Alvedon Film-coated Tablet) (Reference 1)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Time to Reach Maximum Concentration (tmax) for Paracetamol ODT (Test) Vs Paracetamol (Alvedon Film-coated Tablet) (Reference 1)
timeFrame: 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
measure: Cmax for Paracetamol ODT (Test) Vs Paracetamol (Pandol Film-coated Tablet) (Reference 2)
timeFrame: 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
measure: AUC0-tlast for Paracetamol ODT (Test) Vs Paracetamol (Pandol Film-coated Tablet) (Reference 2)
timeFrame: 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
measure: tmax for Paracetamol ODT (Test) Vs Paracetamol (Pandol Film-coated Tablet) (Reference 2)
timeFrame: 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:
measure: Area Under the Plasma Concentration Versus Time Curve Calculated From Time Zero to Infinity [AUC (0-inf)] for Paracetamol ODT (Test)
timeFrame: 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
measure: AUC (0-inf) for Paracetamol (Alvedon Film-coated Tablet) (Reference 1)
timeFrame: 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
measure: AUC (0-inf) for Paracetamol (Pandol Film-coated Tablet) (Reference 2)
timeFrame: 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
measure: AUCexpol% for Paracetamol ODT (Test)
timeFrame: 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
measure: AUCexpol% for Paracetamol (Alvedon Film-coated Tablet) (Reference 1)
timeFrame: 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
measure: AUCexpol% for Paracetamol (Pandol Film-coated Tablet) (Reference 2)
timeFrame: 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
measure: Apparent Terminal Elimination Rate Constant Determined by Log-linear Regression (Lz) for Paracetamol ODT (Test)
timeFrame: 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
measure: Lz for Paracetamol (Alvedon Film-coated Tablet) (Reference 1)
timeFrame: 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
measure: Lz for Paracetamol (Pandol Film-coated Tablet) (Reference 2)
timeFrame: 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
measure: Apparent Terminal Elimination Half-life (t1/2) for Paracetamol ODT (Test)
timeFrame: 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
measure: t1/2 for Paracetamol (Alvedon Film-coated Tablet) (Reference 1)
timeFrame: 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
measure: t1/2 for Paracetamol (Pandol Film-coated Tablet) (Reference 2)
timeFrame: 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
Other outcomes:
Locations:
city: Erfurt
country: Germany
facility: SocraTec R&D GmbH
state: Thuringia
Study officials:
References: