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

Objective Compare the efficacy and tolerability of the dual‐opioid, Q8003 ® (morphine/oxycodone combination) 12 mg/8 mg to morphine 12 mg or oxycodone 8 mg 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 L ikert 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 182.7 mg from Q8003 12 mg/8 mg, 92.4 mg for morphine 12 mg, and 92.1 mg for oxycodone 8 mg. SPID from baseline over 24 hours and SPID from baseline over 48 hours were significantly ( P  < 0.02) higher for Q8003 12 mg/8 mg vs morphine 12 mg or oxycodone 8 mg. Significantly ( P  < 0.015) 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 12 mg, and 2.3% with oxycodone 8 mg, 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.