Background & Aims
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) and has been used over-the-counter (OTC) for acute pain since 1983. Prolonged release (PR) formulations are therapeutically useful for situations where more than several doses of Immediate release (IR) treatment are anticipated to be necessary, such as for relief from back, muscular or joint pain which may resolve in a few days and still treatable OTC. This ibuprofen PR was developed to reduce dosing frequency yet deliver similar exposure to active ibuprofen with that seen from IR, offering sustained analgesia for up to 12 hours with a less fluctuating pharmacokinetic profile (1,2).
In this study, the primary aim was to evaluate analgesic superiority of ibuprofen PR over 12 hours compared with placebo in patients with moderate-to-severe pain following dental surgery. Key secondary aims were to compare analgesic performance of ibuprofen PR with ibuprofen IR tablets over 24 hours, and to evaluate its safety and tolerability.
Methods
A single-centre, randomised, double-blind, double-dummy, multiple-dose, active and placebo-controlled study in moderate-to-severe pain after dental surgery. Patients were assigned to either 2 x 300 mg ibuprofen PR every 12 hours, 2 × 200 mg ibuprofen IR every 8 hours, or placebo, in a 3:3:1 ratio.
The primary efficacy endpoint was the summed pain intensity difference (SPID) over 0 to 12 hours (SPID12), and secondary evaluations included SPID4, SPID8 and SPID24. To assess time to perceptible pain relief, time to meaningful pain relief, and time to onset of analgesia, a double stopwatch technique was used. The secondary endpoint, pain intensity difference (PID), was calculated as the difference in Numerical Rating Scale (NRS) pain intensity between each timepoint and Time 0. Safety monitoring was conducted for all subjects and all adverse events (AEs) and serious adverse events (SAEs) were recorded.
Results
258 patients completed the study and no safety concerns were identified.
SPID12 scores were significantly different between ibuprofen PR and placebo (34.05 [95% CI, 26.72–41.38], p < 0.0001). All least squares (LS) mean SPID scores were significantly greater for both ibuprofen PR and IR compared with placebo (p < 0.0001) for all timepoints. The SPID24 scores for ibuprofen PR compared with IR were similar and the difference in LS means was not statistically significant (–5.67 [95% CI -16.30, 4.97], p = 0.2952). From the 30-minute timepoint, the mean PID scores were significantly higher for both ibuprofen groups than for placebo throughout the study. The median time to first perceptible relief was significantly shorter in the ibuprofen PR group (0.47 [95% CI, 0.39–0.51] hours) and in the IR group (0.46 [95% CI, 0.35–0.50] hours) compared to the placebo group (1.01 [95% CI, 0.46–not estimable] hours, P-value = 0.0380 and <0.0001 for ibuprofen PR and IR versus placebo, respectively).
Conclusions
Overall, the analgesic performance of ibuprofen PR tablets was superior to placebo in subjects experiencing acute moderate-to-severe pain after third molar extraction over 12 hours post initial dose. The overall total analgesic effect, peak analgesic effect, onset and duration of action and the subject’s overall assessment of the study drugs was similar for both the ibuprofen PR (2 doses) and ibuprofen IR tablets (3 doses), and superior compared to placebo over 24 hours post initial dose. One dose of ibuprofen PR had significantly superior efficacy at all time points from 30 minutes to 12 hours, compared with placebo. Mean PID scores reflected the sustained PK profile of the PR formulation. The ibuprofen PR was well tolerated with a good safety profile and the extent of pain relief was substantial compared to placebo, in line with what has been reported for other effective analgesic products (1) and was clinically meaningful.
References
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