Pharmacokinetic study of four orally formulated combinations of acetaminophen and ibuprofen 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 four‐way cross‐over sequence: ‐ Treatment A: oral suspension containing 1000 mg acetaminophen + 300 mg ibuprofen in 31.25 mL ‐ Treatment B: powder sachet containing 1000 mg acetaminophen + 300 mg ibuprofen for oral solution ‐ Treatment C: tablets providing total dose of 1000 mg acetaminophen + 300 mg ibuprofen ‐ Treatment D: tablets providing total dose of 975 mg acetaminophen + 292.5 mg ibuprofen The administration of doses will be supervised on site. All treatments will be administered under fed conditions. Participants will be fasted for at least 10 hours overnight and receive a standardized breakfast served 30 minutes prior to study drug administration. This breakfast will supply around 967 kcal about 50% of which are fat calories. A standardized meal will be served approximately 5 hours after dosing and a snack will be provided approximately 9 hours after study drug administration. Water will be restricted for 1 hour pre‐dose and 1 hour post‐dose (with the exception of water administered as part of dosing). Administration ‐ Oral Suspension formulation: 31.25 mL of the oral suspension will be dispensed for consumption. Any residue remaining after initial administration will be resuspended with 240 mL of water and consumed. ‐ Powder Sachet formulation: contents of the sachet will be dissolved in 240 mL hot water and consumed once cold. ‐ Tablet Formulations: will be administered with 240 mL of water. Dose‐frequency is single doses of four different formulations separated by a washout period of 3 days. All participants will complete the four periods in cross‐over fashion. CONDITION: Pain relief PRIMARY OUTCOME: To determine the pharmacokinetic parameters (Cmax, AUC(0‐t), AUC(0‐inf), Tmax, Kel, t1/2) of acetaminophen and ibuprofen and compare between four treatment groups, under fed conditions. SECONDARY OUTCOME: An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical assessments. ; Known NSAID adverse effects (i.e. GI ulceration, indigestion/stomach pain, GI bleeding, bronchospasm, water retention, renal failure, skin reactions and thromboembolic events), and known adverse effects of acetaminophen (i.e. clinical evidence of hepatotoxicity) will be compared between groups. ; Adverse events will continue to be assessed up to 7 days after the last dose of the study medication by spontaneous reporting and at a final follow‐up phone call. INCLUSION CRITERIA: Healthy subjects, 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 3 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 12‐lead ECG recording), urinalysis, and blood biochemical, haematological and serological examinations.