Background: Celecoxib-tramadol co-crystal (CTC) is a first-in-class analgesic co-crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co-crystal structure, compared with its active constituents administered alone/concomitantly.
Aim: We evaluated CTC in moderate-to-severe acute postoperative pain.
Materials and methods: This randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate-to-severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac-tramadol hydrochloride] every 12 h), tramadol (50 mg every 6 h), celecoxib (100 mg every 12 h), or placebo for 48 h. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0-48 h sum of pain intensity differences (SPID0-48) in all randomized patients. Pain intensity was assessed on a 0-10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals.
Results: In 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n = 184), tramadol (n = 183), celecoxib (n = 181), or placebo (n = 89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID0-48 (least-squares mean: -139.1 [95% confidence interval: -151.8, -126.5]) than tramadol (-109.1 [-121.7, -96.4]; p < 0.001), celecoxib (-103.7 [-116.4, -91.0]; p < 0.001), or placebo (-74.6 [-92.5, -56.6]; p < 0.001). Total treatment-emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug-related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths.
Conclusion: CTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the United States.
Keywords: acute pain; analgesia; celecoxib; co-crystal; efficacy; pain; postoperative; postoperative pain; safety; tramadol.
© 2022 Esteve Pharmaceuticals S.A, Premier Research and The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.