A phase 3, randomized, double-blind comparison of analgesic efficacy and tolerability of Q8003 vs Oxycodone or morphine for moderate-to-severe postoperative pain following bunionectomy surgery

摘要

Objective: Compare the efficacy and tolerability of the dual-opioid, Q8003? (morphine/oxycodone combination) 12mg/8mg to morphine 12mg or oxycodone 8mg in subjects following bunionectomy surgery. Design: This was a randomized, double-blind study. Setting: Hospitalized patients. Patients: Healthy men or women aged ≥18 years with moderate or severe pain (score ≥2 on a 4-point Likert scale) and ≥4 on the 11-point numerical pain rating scale following surgery. Interventions: Study medication was initiated after surgery and was given for 48 hours. Outcomes: The primary efficacy variable was mean sum of the pain intensity difference (SPID) scores from the postsurgical baseline. Results: Five hundred twenty-two subjects were randomized; 31 (5.9%) discontinued, including 19 (3.6%) for adverse events. The mean total morphine equivalent dose (MED) was 182.7mg from Q8003 12mg/8mg, 92.4mg for morphine 12mg, and 92.1mg for oxycodone 8mg. SPID from baseline over 24 hours and SPID from baseline over 48 hours were significantly (P0.02) higher for Q8003 12mg/8mg vs morphine 12mg or oxycodone 8mg. Significantly (P0.015) fewer subjects in the Q8003 group required ibuprofen rescue medication, used lower doses of rescue medication, and had a longer median time to first use of rescue medication. Oxygen desaturation 90% occurred in 5.3% with Q8003, 2.8% with morphine 12mg, and 2.3% with oxycodone 8mg, and the cumulative median dose at first desaturation was twofold greater with Q8003. Conclusion: Q8003 provided superior efficacy to its individual components at twice the MED with only a modest increase in the incidence of adverse events.