US Medical Affairs Fellow Haleon Agawam, Massachusetts
Background: Ibuprofen (IBU) and acetaminophen (APAP) are oral analgesics with distinct mechanisms of action (MoA). Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), which targets the cyclooxygenase (COX)-1 and COX-2 enzymes peripherally to prevent prostaglandin formation needed to send pain signals to the brain. Acetaminophen is a centrally acting analgesic that is thought to block prostaglandin and other brain signal factors to raise the pain threshold. Ibuprofen (125 mg) and APAP (250 mg), as two distinct active ingredients, when combined in a fixed dose combination (FDC) offer efficacy advantages and potential tolerability differentiation.
Purpose/Objectives: Ibuprofen (IBU) 125 mg and acetaminophen (APAP) 250 were formulated in a FDC, dosed as two tablets every 8 hours. The FDC was studied in a Dental Pain Clinical Study (third molar extraction) to evaluate its effectiveness treating acute pain. The study subjects had moderate to severe pain at baseline. In this analysis, we evaluated the treatment response of subjects with ‘moderate pain’ compared to those with ‘severe pain
Methods: The single dose dental pain study included four arms (IBU/APAP 250/500 mg [n=172], IBU 250 mg [n=175], APAP 650 mg [n=165], and placebo (PBO) [n=56]). Key study endpoints were summary of pain intensity difference (SPID 0-8 hours), time to meaningful pain relief (MPR], and treatment failure at 8 hours (TF8), which we compared in subjects with moderate pain (n=255) versus severe pain (n=313) in this analysis.
Results: Moderate pain patient results: 1) mean SPID 0-8 hours was significantly better with FDC (29.8) than APAP (19.1 [p< 0.001]), IBU (21.7 [p=0.006]), and PBO (4.9 [p< 0.001]); 2) median time (minutes) to MPR was faster with FDC (52.7) than APAP (53.0 [p=0.741]), IBU (59.0 [p=0.084]), and PBO ( >720 [p< 0.001]); 3) percent with TF8 was less with FDC (23.1%) than APAP (45.1% [p=0.004]), IBU (32.5% [p=0.164]), and PBO (57.7% [p=002]). Severe pain patient results: 1) mean SPID 0-8 hours was better with FDC (38.1) than APAP (19.7 [p< 0.001]), IBU (34.8 [p=0.233]), and PBO (3.4 [p< 0.001]); 2) median time (minutes) to MPR was faster with FDC (45.5) than APAP (60.8 [p=0.018]), IBU (69.7 [p=0.018]), and PBO ( >720 [p< 0.001]); 3) percent with TF8 was less with FDC (25.5%) than APAP (56.4% [p< 0.001]), IBU (33.7% [p=0.213]), and PBO (80.0% [p< 001]). FDC, APAP, IBU, and PBO were well tolerated with few adverse
Conclusions/Implications for future research and/or clinical care: FDC IBU/APAP 250/500 mg demonstrated in this analysis that it was effective in moderate and severe pain. Importantly, effectiveness of the FDC was maintained in the subset with severe pain at baseline. Dental pain is a recognized model for evaluating treatments for acute pain, and this study confirmed the effectiveness of the FDC IBU/APAP 250/500 mg. Equally important was the good tolerability of the product demonstrated in the study.
