The primary objective of this study is to compare the efficacy of a combination product containing ibuprofen 400 mg and caffeine 100 mg versus either ingredient alone as well as placebo for the treatment of post-surgical dental pain over an eight-hour period followed by a single dose of study medication (study stage 1). A secondary objective is to evaluate efficacy of multiple doses of the combination in comparison to ibuprofen alone over a 5-day post-surgical period (study stage 2).
<b>BACKGROUND: </b>Ibuprofen is an effective analgesic treatment with a ceiling effect at doses above 400 mg. This study compared the combination of ibuprofen 400 mg and caffeine 100 mg with ibuprofen 400 mg monotherapy, caffeine and placebo in the analgesic treatment of moderate to severe acute dental pain following third molar extraction.<b>METHODS: </b>Phase III, active-/placebo-controlled, double-blind, single-centre, two-stage, parallel-group study in adult patients with at least moderate baseline pain intensity. Primary endpoint was defined as the time-weighted sum of pain relief and pain intensity difference over 8 h (SPRID0-8 h), secondary endpoints included duration of pain relief, time to meaningful pain relief and more.<b>RESULTS: </b>N = 748 patients were enrolled and N = 562 treated. Mean baseline pain intensity was 7.7 on a 0-10 numerical rating scale. Analysis of SPRID0-8 h demonstrated superior analgesic effects for a single dose of ibuprofen/caffeine versus ibuprofen, caffeine and placebo over 8 h, rescue medication in this stage was requested by more patients on ibuprofen (32.5%) than on ibuprofen/caffeine (16.0%). Median time to meaningful pain relief was shorter for ibuprofen/caffeine (1.13 h) compared with ibuprofen (1.78 h; p = 0.0001). More patients on ibuprofen/caffeine than on ibuprofen reported meaningful pain relief. Adverse events were infrequent and mostly mild or moderate across treatment groups. Tolerability was rated as 'very good' or 'excellent' by most patients in both treatment groups.<b>CONCLUSION: </b>This study demonstrated clinically relevant superiority of ibuprofen/caffeine over monotherapy with ibuprofen in patients with acute dental pain. All treatments were well tolerated.<b>Significance: </b>This trial showed superior efficacy of 400/100 mg ibuprofen/caffeine, compared to 400 mg ibuprofen alone, for treating acute pain, reflecting that caffeine is an effective analgesic adjuvant. Data on efficacy of 400 mg ibuprofen combined with caffeine for the treatment of acute pain were not available yet.
<b>INTRODUCTION: </b>A fixed dose combination (FDC) of ibuprofen 400 mg and caffeine 100 mg has been shown to be more effective than ibuprofen 400 mg alone for the treatment of acute postoperative dental pain in a phase III randomised controlled trial. A post hoc subgroup analysis of the primary data from an active-/placebo-controlled, double-blind, single-centre, parallel-group study was conducted in patients with moderate or severe baseline pain.<b>METHODS: </b>After dental surgery, patients with moderate or severe pain, which was determined on a 4-point verbal rating scale ('no pain' to 'severe pain'), received a single dose of ibuprofen 400 mg/caffeine 100 mg FDC, ibuprofen 400 mg, caffeine 100 mg or placebo. Pain relief (PAR) and pain intensity were assessed 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7 and 8 h after administration of study medication. The primary study endpoint was the time-weighted sum of PAR and pain intensity difference (PID) from pre-dose baseline, summed for all post-dose assessment times from 0 to 8 h (SPRID0-8h).<b>RESULTS: </b>There were 237 patients with moderate pain and 325 with severe pain at baseline. SPRID0-8h was significantly improved with the FDC versus ibuprofen, caffeine and placebo in the moderate and severe pain subgroups. Adjusted mean SPRID0-8h difference for the FDC versus ibuprofen was 18.19 (p < 0.0001) for patients with moderate pain and 7.70 (p = 0.0409) for patients with severe pain. With the exception of the 7-h measurement in patients with moderate pain, PID was significantly improved with the FDC versus ibuprofen at all measured time points from 0.5 to 8 h. In the severe pain subgroup, PID was significantly improved for the FDC versus ibuprofen from 0.5 to 3 h post-dose, but was not significantly different thereafter.<b>CONCLUSION: </b>The enhanced analgesic efficacy of ibuprofen/caffeine FDC versus ibuprofen is most pronounced in patients with moderate intensity pain at baseline, and also evident in patients with severe baseline pain.<b>Trial Registration: </b>ClinicalTrials.gov identifier, NCT01929031.
The primary objective of this study is to compare the efficacy of a combination product containing ibuprofen 400 mg and caffeine 100 mg versus either ingredient alone as well as placebo for the treatment of post-surgical dental pain over an eight-hour period followed by a single dose of study medication (study stage 1). A secondary objective is to evaluate efficacy of multiple doses of the combination in comparison to ibuprofen alone over a 5-day post-surgical period (study stage 2).
