Poster Number-46 - Celecoxib Oral Solution in the Acute Treatment of Migraine: Pooled Efficacy and Safety Results From 2 Randomized Placebo-controlled Trials

Celecoxib Oral Solution in the Acute Treatment of Migraine: Pooled Efficacy and Safety Results From 2 Randomized Placebo-controlled Trials

Nonsteroidal anti-inflammatory drugs (NSAIDs) have established efficacy and are commonly used in acute treatment of migraine headache. Celecoxib oral solution (Elyxyb) is a selective cyclo-oxygenase (COX)-2 inhibitor that provides unique pharmacokinetic benefits by employing a self-microemulsifying drug delivery system (SMEDDS) technology, making it a rapidly absorbed oral solution formulation (T_max=42 min) that may be beneficial for patients seeking immediate migraine relief. Two recently published phase 3 clinical trials have established the safety and efficacy of celecoxib oral solution, leading to the US Food and Drug Administration approval of celecoxib oral solution for the acute treatment of migraine headache with or without aura. The purpose of this pooled analysis is to assess the co-primary efficacy outcomes from these 2 clinical trials that compare celecoxib oral solution and placebo for acute treatment of migraine in adults with or without aura.

Methods:

Adults with 2 to 8 migraine attacks per month of moderate to severe pain intensity were enrolled in these 2 identical, randomized, double-blind, placebo-controlled clinical trials (ClinicalTrials.gov identifiers: NCT03006276 and NCT03009019). Subjects were randomized (1:1) and administered either celecoxib oral solution (120 mg) or placebo within 1 hour of migraine onset. The patient-reported co-primary efficacy outcomes at 2 hours postdose comprised freedom from headache pain (2hPF) and most bothersome symptom (2hMBS-F), which were recorded in an eDiary. Freedom from headache pain was defined as a reduction from predose moderate (grade 2) or severe (grade 3) pain to none (grade 0). Freedom from most bothersome symptom is defined as a reduction of the subjects’ most bothersome symptom (chosen among nausea, photophobia, or phonophobia at screening) from predose moderate (grade 2) or severe (grade 3) to none (grade 0). The safety population included all dosed patients with recorded data. Pooled results from participants in the intent-to-treat full-analysis set populations of both studies were used to calculate odds ratios (ORs) with 95% Wald confidence intervals (CIs) for the 2-hour time point and all preceding time points.

Results:

Both co-primary efficacy outcomes achieved statistical significance: 2hPF (34.3% celecoxib oral solution vs 24.0% placebo; p=0.0002; OR, 1.66; 95% CI, 1.28-2.16; n=1112) and 2hMBS-F (57.3% celecoxib oral solution vs 43.7% placebo; p< 0.0001; OR, 1.73; 95% CI, 1.35-2.20; n=1060). For most bothersome symptom freedom, significant improvement was first observed at 45 minutes postdose (28.7% celecoxib oral solution vs 22.4% placebo; p=0.023; OR, 1.39; 95% CI, 1.05-1.84; n=1034) and at all time points thereafter through 2 hours postdose. Freedom from headache pain first achieved significance at 1 hour postdose (18.2% celecoxib oral solution vs 12.5% placebo; p=0.0095; OR, 1.56; 95% CI, 1.11-2.17; n=1095). Sensitivity and subgroup analyses showed no significant differences by sex, race, age, or moderate vs severe predose pain. Extensive safety analyses identified no safety concerns in either clinical trial.

Conclusion:

This pooled analysis of 2 identical placebo-controlled clinical trials illustrated that significantly more subjects experienced freedom from headache pain and freedom from the most bothersome symptoms following celecoxib oral solution (120 mg) administration, compared with placebo at 2 hours postdose. Post hoc analysis showed significantly improved ORs and 95% CIs at 45 minutes postdose for freedom from most bothersome symptom and at 1 hour postdose for freedom from headache pain in subjects receiving celecoxib oral solution. These findings support the hypothesis that the rapid absorption of celecoxib oral solution facilitated by the use of SMEDDS technology, and the liquid formulation translates into fast onset of migraine-related pain relief with a favorable safety and tolerability profile for the acute treatment of migraine in adults.

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