Randomized Open‑label Crossover Bioavailability Study of Paracetamol/Naproxen Fixed‑Dose Combination (MFC‑06285) vs Individual Paracetamol and Naproxen in Healthy Adults
- Trial ID
- 2025-524663-20-00
- Protocol
- 300259
- Sponsor
- Haleon CH SARL
Trial statistics
Objectives
Primary objective: To assess the bioavailability of paracetamol and naproxen from the fixed‑dose combination tablet (500 mg/125 mg) compared with separate reference products (naproxen 250 mg and paracetamol 500 mg) under fasted conditions, thereby providing exposure data essential for evaluating therapeutic equivalence. Secondary objectives:
- Compare the bioavailability of the combination tablet in fasted versus fed states.
- Determine differences in Tmax for paracetamol and naproxen between the combination tablet and the individual reference products under fasted conditions.
- Characterise the single‑dose pharmacokinetic profile of paracetamol after administration of the reference paracetamol tablet.
- Characterise the single‑dose pharmacokinetic profile of naproxen after administration of the reference naproxen tablet.
- Describe the overall pharmacokinetic profile of both active ingredients following administration of the combination tablet in fasted and fed conditions.
- Provide a descriptive assessment of safety and tolerability for the combination tablet and the reference products based on observed adverse events.
Participants
The trial enrolled adult male and female individuals classified as healthy volunteers, aged 18 to 55 years. The sponsor did not provide the total number of participants. Enrollment required written informed consent, a body mass index between 18.5 and 30.0 kg/m2, and a minimum body weight of 50 kg for both sexes. Participants were required to be in generally good physical health without clinically relevant abnormalities on medical history, physical examination, 12‑lead ECG, or laboratory tests. Women of child‑bearing potential had to use a highly effective contraceptive method throughout the study and for at least 7 days after the final dose. Selection was based on these inclusion criteria, and individuals with conditions that could affect the study outcomes were excluded.
Plans and Procedures
The study is a randomized, open‑label, single‑center, single oral dose, four‑treatment, four‑period, four‑sequence crossover trial conducted in healthy adult volunteers to evaluate the bioavailability of a fixed‑dose combination of paracetamol 500 mg/naproxen 125 mg compared with separate reference products (paracetamol 500 mg and naproxen 250 mg). Participants are screened during an initial visit, then receive each of the four treatments in a pre‑defined sequence with an appropriate washout interval between periods; the sequence includes fasted administration of the test product, fasted administration of each reference, and fed administration of the test product. Blood samples for pharmacokinetic analysis are collected after each dose to determine AUC₀‑tlast and Cmax for both active ingredients as the primary endpoints, with secondary endpoints including tmax, AUC₀‑inf, half‑life, and tolerability assessments. The overall involvement for each participant spans approximately four weeks, encompassing the screening visit, four dosing visits, associated follow‑up sampling, and a final end‑of‑study visit. Early termination may occur if a participant experiences a serious adverse event, withdraws consent, fails to comply with the dosing or washout schedule, or exhibits clinically significant laboratory abnormalities. The recruitment period is scheduled from 25 September 2026 to 21 November 2026, and the study is classified as a Phase I bioavailability trial.
Treatment
The test medication, identified as Paracetamol 500 mg and Naproxen 125 mg Tablet MFC‑06285, is a film‑coated tablet containing 500 mg of paracetamol and 125 mg of naproxen per tablet. It is administered orally as a single dose of two tablets, delivered under both fasted and fed conditions in a crossover design. Dosing is directly observed, and timing of administration is recorded to ensure compliance with the study schedule.
The first comparator consists of Panadol Advance 500 mg Tablets, a film‑coated tablet formulation delivering 500 mg of paracetamol per tablet. Participants receive a single oral dose of two tablets in the fasted state. Ingestion is supervised, and adherence is verified through observation and documentation of the exact dosing time.
The second comparator is Naprosyn 250 mg comprimidos, a tablet containing 250 mg of naproxen. A single oral dose of one tablet is administered under fasted conditions. Dosing is observed, and compliance is monitored by recording the time of intake and confirming complete tablet consumption.
All study arms involve a single oral administration, and participant compliance is ensured by supervised dosing and accurate timestamping of drug intake. The primary objective of the trial is to assess the bioavailability of the active ingredients across the test and comparator treatments.
Efficacy
The primary efficacy assessment will compare the AUC0‑tlast and Cmax of paracetamol and naproxen following fasted administration of the test formulation versus each reference product. Plasma concentration‑time profiles will be generated for each treatment period, and the primary pharmacokinetic parameters will be derived using standard non‑compartmental analysis.
Secondary efficacy evaluations will include the tmax of both active ingredients after fasted administration of the test versus reference products, as well as the comparison of AUC0‑tlast, Cmax and tmax for the test formulation under fasted and fed conditions. Additional pharmacokinetic descriptors (tmax, AUC0‑inf, %AUCex, λz, t½) will be calculated for paracetamol and naproxen after administration of each treatment. Tolerability will be assessed through the incidence of adverse events, vital‑sign measurements, and protocol‑specified safety laboratory evaluations. All analyses will be performed on data collected from healthy adult participants in accordance with the study’s statistical analysis plan.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed, including the genotyping to be performed.
- Male or female participant who, at the time of screening, is between the ages of 18 and 55 years, inclusive.
- Participant who is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Healthy participant, which is defined as in general good physical health, as judged by the investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG or clinical laboratory tests.
- Body Mass Index (BMI) of 18.5 to 30.0 kg/m2; and a total body weight ≥ 50.0 kg for males and ≥ 50.0 kg for females.
- Female participant of childbearing potential 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.
Exclusion Criteria
- Existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient.
- Existing hepatic, pancreatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient.
- Existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient.
- 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, e.g., appendectomy and herniorrhaphy).
- History of inflammatory bowel disease or gastrointestinal bleeding including peptic ulcers.
- Existing metabolic (e.g. diabetes mellitus, metabolic syndrome), endocrine and/or immunologic diseases (e.g. autoimmune disorders) or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient.
- Acute and/or history of relevant CNS and/or psychiatric disorders.
- Clinically relevant chronic or acute infectious illnesses or febrile infections within two weeks prior to start of the study.
- Status of glutathione depletion due to metabolic deficiencies (i.e. due to eating disorders, cystic fibrosis, HIV infection, starvation, cachexia).
- Evidence of urinary obstruction (e.g. due to benign prostate hyperplasia) or difficulty in voiding at screening.
- History of severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator.
- Known allergic reactions (e.g., bronchospasm, rhinitis, angioedema, or urticaria) to the active ingredients used, to acetylsalicylic acid or other NSAIDs, or to constituents of the pharmaceutical preparations.
- Systolic blood pressure < 90 or > 139 mmHg.
- Diastolic blood pressure < 50 or > 89 mmHg.
- Heart rate < 50 bpm or > 90 bpm.
- QTc interval > 450 ms for men and > 470 ms for women.
- Screening laboratory results demonstrate blood urea nitrogen (BUN) (≥ 35 mg/dL) or instead urea (≥ 5.85 mmol/l); serum creatinine > 0.1 mg/dL above the laboratory reference upper limit, or estimated glomerular filtration rate (eGRF) ≥90 mL/min/1.73 m²; additionally the presence of protein or blood on urine dipstick testing at baseline is grounds for exclusion.
- In case where screening values of gamma-glutamyl transferase (GGT), alanine aminotransferase (ALP), or aspartate aminotransferase (AST) exceed ≥ 1.2 ULN, or if bilirubin is > 20% ULN - an exception to the to the bilirubin criterion is made for subjects with documented Gilbert's syndrome and otherwise normal ALT, AST and ALP, where bilirubin may be up to 2x ULN.
- Hemoglobin value < 12.0 g/dL for males and < 11.5 g/dL for females, corresponding to 7.452 mmol/l or 7.142 mmol/l for males and females, respectively.
- Positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test, anti-HCV-test or HBc-Ab (IgG + IgM).
- Laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator.
- Acute or chronic diseases which may interfere with the pharmacokinetics of the IMP.
- History of or current alcohol dependence.
- Positive alcohol, cotinine or drug test at screening examination.
- Regular intake of alcoholic food or beverages of ≥ 24 g pure ethanol for male or ≥ 12 g pure ethanol for female per day.
- History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
- Blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the participant.
- Current smoker, defined as the use of tobacco or nicotine products during the 3 months prior to screening until admission to the unit or a positive urine cotinine test at screening
- Participants who are on a diet which could affect the pharmacokinetics of the active ingredient.
- Participants unwilling or unable to comply with the Lifestyle Considerations described in this protocol.
- Any history of long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.
- Participation in a clinical trial with administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the participant.
- Simultaneous participation in another clinical trial with active ingredients.
- Participants, who report a frequent occurrence of migraine attacks.
- Positive pregnancy test at screening examination or at hospitalisation.
- Pregnant or lactating women.
- Female participants who do not agree to apply highly effective contraceptive methods (highly effective contraceptive methods are defined in chapter 13.2.1 of the clinical trial protocol).
- Participant is vulnerable such as detained or committed to an institution by a court of law or by legal authorities or close affiliation with the sponsor or the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee of or student at the investigational site, employee of sponsor`s affiliates).
- Participants suspected or known not to follow instructions.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Yet Recruiting | 25 Sept 2026 | 52 |
Sites & Investigators
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Panadol Advance 500 mg Tablets | Comparator | TABLETS | ORAL | — | — | PRD4295643 |
Paracetamol 500 mg and Naproxen 125mg Tablet MFC-06285 | Test | TABLET | ORAL | — | — | PRD13133973 |
Naprosyn 250 mg comprimidos | Comparator | COMPRIMIDOS | ORAL | — | — | PRD7454539 |