Pharmacokinetic study of acetaminophen and ibuprofen, oral formulations, in healthy volunteers under fed conditions

INTERVENTION: Each participant will be randomly allocated to receive a single dose of each of the following treatments in a balanced three‐way cross‐over sequence: Treatment A: 975 mg acetaminophen and 292.5 mg ibuprofen Treatment B: 650 mg acetaminophen and 75 mg tramadol hydrochloride Treatment C: 800 mg ibuprofen. All treatments will be administered as oral tablets, with a full glass of water, in fed conditions. The administration of all doses will be supervised on site. The washout period between the periods is 3 days. Dose frequency ‐ single dose, administered as oral tablets. All participants complete all three periods (treatments A‐C) in a cross‐over fashion. Participants will be fasted for at least 10 hours overnight before dosing and receive a standardized breakfast served 30 minutes prior to study drug administration. This breakfast will supply around 967kcal about 50% of which are fat calories. A standardized meal will be provided approximately at 5 hours after dosing. Also a snack will be provided approximately at 9 hours after the study drug administration. Meal plans will be identical in all periods and will be served at the same time. Water will be restricted for 1 hour pre‐dose and 1 hour post‐dose. CONDITION: Pain relief PRIMARY OUTCOME: To determine and compare dose‐normalized acetaminophen and ibuprofen related pharmacokinetic parameters (Cmax,AUC(0‐t), AUC(0‐inf), Tmax, t1/2)betweeen all treatment groups, under fed conditions SECONDARY OUTCOME: Safety will be evaluated during each study period and for 7 days following last dose of study drug administration. An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical assessments. ; Known NSAID adverse events (i.e gastrointestinal ulceration, indigestion, stomach pain, GI bleeding, bronchospasm, water retention, renal failure, skin reactions and thromboembolic events)and known acetaminophen adverse effects (i.e.clinical evidence of hepatotoxicity) will be summarized by treatment groups. Adverse events will continue to be assessed up to 7 days after the last dose of the study medication by spontaneous reporting and a final follow‐up call. INCLUSION CRITERIA: Healthy volunteers, males and females aged 18 to 50 years of age. Females must be sterile or using adequate contraception. Participants must not have taken any prescription medications for at least 14 days or over‐the‐counter medications for at least 7 days before the start of each study phase, with the exception of oral contraceptives and the study medication. All subjects must be deemed healthy on the basis of a medical history, physical exam (including vital signs and ECG recording), urinalysis, and blood biochemical and haematological examinations.