A pharmacokinetic study of acetaminophen, ibuprofen, and xylometazoline hydrochloride in healthy volunteers under fasting conditions.

INTERVENTION: Each participant will be randomly allocated to receive a single dose of each of the intervention treatments, and the comparator treatment under fasting conditions in a three‐way crossover sequence: Intervention Treatments: Treatment A: Paracetamol 500 mg & Ibuprofen 150mg Film‐Coated Tablets (500 mg acetaminophen + 150 mg ibuprofen per film coated tablet) Administration: Two tablets (given at the same time) as a single dose (total dose 1000 mg acetaminophen + 300mg ibuprofen) will be administered orally with 240 mL of water. Treatment B: Xylometazoline hydrochloride (1 mg/mL; 0.138 mL per spray; 0.138 mL of 1mg/mL xylometazoline hydrochloride will give a calculated dose of 0.138 mg of xylometazoline hydrochloride per spray). Administration: One spray per nostril, a total of two sprays will be administered as a single dose (total of 0.276 mL of xylometazoline hydrochloride delivered, total calculated dose of 0.276 mg of xylometazoline hydrochloride). Participants will be fasted for at least 10 hours overnight before dosing and for 4 hours after dosing. Water will be restricted for 1 hour pre‐dose and 1 hour post‐dose (with the exception of water administered as part of dosing). The test product will be administered under the site staff's supervision and the exact dosing time will be documented. There will be three study periods each separated by a washout period of at least 7 days between two consecutive periods and a subsequent 7 days of final follow‐up period. CONDITION: Anaesthesiology ‐ Pain management Pain Relief; ; Pain Relief PRIMARY OUTCOME: To evaluate and compare the pharmacokinetic parameters (Cmax, AUC0‐t, AUC0‐inf, Tmax, Kel and t1/2el) of acetaminophen, ibuprofen and xylometazoline hydrochloride when taken separately and when taken together under fasting conditions. [Blood samples will be drawn pre‐dose (0.00 hours) and at 5 minutes (0.083 hours), 10 minutes (0.167 hours), 20 minutes (0.333 hours), 30 minutes (0.50 hours), 45 minutes (0.75 hours) and 1.00, 1.25, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours after study drug administration.] SECONDARY OUTCOME: To compare the safety and tolerability of all treatment groups. ; ; An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical assessments. All adverse events, including any serious adverse events, will be assessed and documented following the participant’s randomization until 7 days after the last dose of the study medication. ; ; Vital signs will be measured pre‐dose and approximately at 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00 and 12.00 hours after study drug administration. Vital signs include heart rate and blood pressure and are taken as per study centre standard protocols. ; ; Haematological and biochemical assessment will be conducted on blood samples taken at the end of each study period. ; ; ; ; ; ; ; ; [Participants will check‐in to the Study Centre the evening prior to study drug administration and will stay for the duration of the Study Period (at least 12 hours after dosing). Each Study Period will consist of a Baseline Period (pre‐dosing) and a Treatment Period. Safety will be evaluated during each study period, and for 7 days following study drug administration. ; ; Vital signs will be measured pre‐dose and approximately at 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00 and 12.00 hours after study drug administration. ; ; Body temperature will be measured before dosing and approximately at 4.00 and 12.00 hours after study drug administration. ; ; Vital signs may be taken at other times if deemed necessary. ; ; An additional blood sample will be taken at the end of each study period for haematology, biochemistry. ; ] INCLUSION CRITERIA: A participant will be eligible for inclusion in this study only if all of the following criteria are met: • Male or female subjects aged between 18 and 50 years, inclusive, on the day of consent. • Voluntarily provide written informed consent before the initiation of any study‐related procedures. • Have a Body Mass Index (BMI) between 18.5 and 30.0 kg/m2. • Have no significant disease (asthma, peptic or gastric ulcer, sinusitis, pharyngitis, gastrointestinal disease, pulmonary disease, renal disorder (impaired renal function), hepatic disorder (impaired hepatic function), cardiovascular disorder, neurological disease such as epilepsy, haematological disorders or diabetes, psychiatric, infective, dermatologic or immunological disorders) as determined by medical history, physical examination and laboratory tests. • Have negative HIV and hepatitis B & C test results. • Be able and willing to abstain from caffeine‐containing beverages (e.g. coffe