Chief Executive Officer CenExel JBR Salt Lake City, Utah
Abstract Title: Efficacy and Safety of Meloxicam Co-Crystal and a Rapid-Absorption Formulation of Meloxicam in The Treatment of Post-Surgical Dental Pain
Background: Oral opioids continue to be a key component of post-surgical pain despite their well-described side effect profile and risk of abuse, misuse and diversion. Meloxicam Co-Crystal (MECC-SA) and a related formulation of Meloxicam are being developed to provide rapid absorption of meloxicam from an oral dose to provide rapid, safe and effective non-opioid analgesia. The designated regulatory authority (e.g., FDA) has not approved the product for marketing in the indication that was the subject of the study.
Purpose/Objectives: One study of each formulation was conducted at the same clinical site, using identical design parameters where feasible, with the objective of evaluating the safety and efficacy of each formulation for the treatment of post-surgical dental pain.
Methods: Subjects undergoing removal of 2 or more 3rd molars were randomized to receive either MECC-SA (10 mg QD, 15 mg QD, 10 mg BID or 15 mg BID) or placebo (study 1); and Meloxicam (1.25mg BID, 5mg BID, 15mg BID) or placebo (study 2). Subjects remained in an inpatient setting for 24 hours to assess efficacy (pain intensity, pain relief, time to onset of pain relief, patient global assessment of efficacy, and rescue medication usage), safety, and pharmacokinetics via serial evaluations over the course of the 24 hours. Subjects were permitted to use hydrocodone/acetaminophen 5/325 mg tablets as rescue treatment for pain.
In both studies, the primary efficacy endpoint was the summed pain intensity difference over 0-24 hours (SPID0-24). SPID0-24 has a range of 0-240 with larger values indicating greater pain reduction. A windowed-last observation carried forward (WLOCF) approach for rescue medication use was utilized where the pain intensity just prior to rescue use was substituted for pain intensities falling within a pre-determined window of time following rescue use; based on the results of the first study, 6 hours was chosen for the second; results are presented for 6 hour rescue censoring in both studies (W6LOCF).
Results: 112 and 110 subjects were randomized and treated in studies 1 and 2, respectively; 110 subjects completed the in-patient portion of each study. In study 1, model-based mean SPID0-24 (95% CI) was 54.9 (38.2, 71.7), 89.6 (75.7, 103.5), 93.4 (84.8, 102.0), 95.6 (87.0, 104.3), 98.1 (85.0, 111.3) for placebo, MECC-SA 10 mg QD, 15 mg QD, 10 mg BID, and 15 mg BID respectively. In study 2, model-based mean SPID0-24 (95% CI) was 52.0 (36.4, 67.5), 70.7 (55.1, 86.3), 86.7 (77.0, 96.4), 94.8 (80.0, 109.6) for placebo, Meloxicam 1.25mg BID, 5mg BID, and 15mg BID respectively. All active arms in study 1 and all but the 1.25mg arm (identified as a “no effect” dose) demonstrated strong statistical separation from placebo.
Both formulations of meloxicam were well-tolerated. Nausea was the most common side effect across all study arms, including placebo.
Conclusions/Implications for future research and/or clinical care: Two randomized, controlled, double blind studies in of novel meloxicam formulations in post-surgical dental pain demonstrated a range of doses provided adequate pain control and statistical separation from placebo. Consistent dose-response was observed in both studies and the placebo results were very similar between the studies. The consistency of the results may be attributable to efforts made to retain as many design aspects as possible between the two studies and the use of the same clinical site for the two studies. There was no dose-dependency observed in the rates of nausea and the results may be driven by individual tolerance and use of the opioid rescue medication.
Additional methodological exploratory analyses may be presented.
Studies investigating the generalizability of these results in post-operative pain for bunionectomy and herniorrhaphy are currently enrolling participants.
