Efficacy and safety of co‐crystal of tramadol‐celecoxib (CTC) in acute moderate‐to‐severe pain after abdominal hysterectomy: A randomized, double‐blind, phase 3 trial (STARDOM2)

Background STARDOM2 is a randomized, double‐blind, phase 3 trial evaluating the efficacy and safety of co‐crystal of tramadol‐celecoxib (CTC)—a first‐in‐class analgesic co‐crystal comprising racemic tramadol hydrochloride and celecoxib in a supramolecular network that modifies their pharmacokinetic properties—for the management of acute postoperative pain (NCT03062644; EudraCT:2016–000593‐38). Methods Patients with moderate‐to‐severe pain following abdominal hysterectomy were randomized 2:2:2:2:2:1 to oral CTC 100 mg (rac‐tramadol hydrochloride 44 mg/celecoxib 56 mg) twice daily (BID); CTC 150 mg (66/84 mg) BID; CTC 200 mg (88/112 mg) BID; immediate‐release tramadol 100 mg four times daily (QID); celecoxib 100 mg BID; or placebo, for 5 days. The primary endpoint was the sum of pain intensity differences over 0–4 h (SPID0–4). Key secondary endpoints were rescue medication use within 4 h, 50% response rate at 4 h, and safety/tolerability. Results Of 1355 patients enrolled, 1138 were randomized (full analysis set) and 1136 treated (safety analysis set). In the prespecified gatekeeping analysis of SPID0–4, CTC 200 mg was not superior to tramadol but showed non‐inferior efficacy (p