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

INTERVENTION: Each participant will receive each of the interventions (Treatment A and B), and the comparator (Treatment C) treatment under fasting conditions in a three‐way cross over sequence. The sequence in which the participants receives each treatment will be randomly allocated. 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). Intervention Treatments: Treatment A: Paracetamol 500mg plus Ibuprofen 150mg fixed‐dose combination film‐coated tablet (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 + 300 mg ibuprofen) will be administered orally with 240 mL of water. Treatment B: Diphenhydramine hydrochloride (50 mg diphenhydramine hydrochloride per tablet). Administration: One tablet will be administered orally with 240 mL of water. 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 so that each participant will receive each of the interventions (Treatment A and B) and the comparator (Treatment C). Each study period will be separated by a washout period of at least 7 days between two consecutive periods. Once the participant completes the final period (Period 3), there is a follow‐up period lasting for 7 days. CONDITION: Anaesthesiology ‐ Pain management Pain ; ; Pain PRIMARY OUTCOME: To evaluate and compare the pharmacokinetic parameters (Cmax, AUC0‐t, AUC0‐inf, Tmax, Kel and t1/2el) of acetaminophen and ibuprofen when taken together in combination 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.] To evaluate and compare the pharmacokinetic parameters (Cmax, AUC0‐t, AUC0‐inf, Tmax, Kel and t1/2el) of acetaminophen, ibuprofen and diphenhydramine hydrochloride when taken together in combination 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.] To evaluate and compare the pharmacokinetic parameters (Cmax, AUC0‐t, AUC0‐inf, Tmax, Kel and t1/2el) of diphenhydramine hydrochloride when taken alone 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 (composite secondary outcome). ; ; ; ; ; ; [Safety will be evaluated during each study period, and for 7 days following study drug administration. ; ; 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. ; ; ; ; A 12‐lead ECG will be conducted just prior to discharge at the final study period. ; Known adverse events of the study treatments (Paracetamol, Ibuprofen and Diphenhydramine) include: Gastrointestinal bleeding/ulceration, Indigestion/stomach pain, bronchospasm, water retention, renal failure, skin reactions, thromboembolic events, hepatotoxicity, drowsiness, dizziness, dry mouth/nose/throat, headache, muscle weakness and thicker nasal discharge. These adverse events will be monitored throughout the study via regular adverse event checks. ; An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical safety assessments (Vital signs, 12‐lead ECG, blood biochemistry and haematology). All adverse events, including any serious adverse events, will be assessed by the Investigators and documented following the participant's randomization until 7 days after the last dose of the study medication. ; 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 (Blood pressure via digital sphygmomanometer, heart rate via holter monitor, manual respiratory rate and body temperature via tympanic thermometer) 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 may be taken at other times if deemed necessary. Body temperature will be measured before dosing and approximately at the following times after dosing: 4th and 12th hour. ; ; Haematological and biochemical assessments will be conducted on blood samples taken at the end of each study period. Haematological assessments include haemoglobin, haematocrit, platelet count, red blood cell count, white blood cell count, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and mean corpuscular volume. Biochemical assessments include urea, creatinine, calculated glomerular filtration rate, glucose, albumin, total protein and liver function tests. ] 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