Abstract
INTRODUCTION: Ibuprofen and acetaminophen provide analgesia via different mechanisms of action and do not exhibit drug-drug interactions; therefore, combining low doses of each may provide greater efficacy without compromising safety. OBJECTIVES: The present study assessed the analgesic efficacy of fixed-dose combinations (FDCs) of ibuprofen/acetaminophen (IBU/APAP) compared with ibuprofen 400 mg and placebo. METHODS: This 12-h, double-blind, proof-of-concept study compared three FDCs of IBU/APAP (200 mg/500 mg, 250 mg/500 mg, and 300 mg/500 mg) with ibuprofen 400 mg and placebo in patients with moderate-to-severe pain following third molar extraction. The primary endpoint was the time-weighted sum of pain relief and pain intensity difference scores from 0 to 8 h after dosing (SPRID[4](0-8)). Time to meaningful pain relief (TMPR), duration of pain relief, and adverse events (AEs) were also assessed. RESULTS: In total, 394 patients were randomized. All active treatments were superior to placebo for SPRID[4](0-8) (all p < 0.001) but not significantly different from ibuprofen 400 mg. Median TMPR with FDCs and ibuprofen (44.5-54.1 and 56.2 min, respectively) was faster than with placebo (> 720 min; all p < 0.001 vs. placebo). Duration of pain relief was similar with the FDCs and ibuprofen 400 mg (9.7 -11.1 h) and longer than with placebo (1.6 h; all p < 0.001). AE incidence was comparable with all treatments. CONCLUSION: Each IBU/APAP FDC provided analgesic efficacy comparable to that with ibuprofen 400 mg and superior to that with placebo. Each FDC provided MPR in < 1 h, duration of pain relief > 9 h, and tolerability similar to that with ibuprofen and placebo. CLINICALTRIALS. GOV REGISTRATION: NCT01559259.