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

Abstract

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 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 182.7 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.

Keywords: Acute Pain; Morphine; Opioid; Opioid-Related Side Effects; Oxycodone; Postoperative Pain; Q8003.

Figure 1

Study flowchart.

Figure 2

Mean sum of the pain intensity difference (SPID) from baseline over 24 hours (SPID₂₄) and SPID from baseline over 48 hours (SPID₄₈) values for Q8003 12 mg/8 mg, morphine 12 mg, and oxycodone 8 mg. For SPID₂₄, Q8003 was significantly better than morphine 12 mg (P = 0.003) and oxycodone 8 mg (P = 0.027). For SPID₄₈, Q8003 was significantly better than morphine 12 mg (P = 0.020) and oxycodone 8 mg (P = 0.019) using the analysis of covariance model.

Figure 3

Sum of the pain intensity difference from baseline over 24 hours by baseline pain intensity score of 5, 6, or 7 on the numerical pain rating scale (NPRS) was used to compare treatment effects and the analysis of covariance included treatment, site, gender, age, body mass index, treatment baseline, and baseline score as fixed-effects.

Figure 4

Least-square mean pain intensity difference (PID) and pain relief difference (PRID) scores at 0–24 and 0–48 hours for each treatment group. P values are from an analysis of covariance model for Q8003 vs morphine or oxycodone.

Figure 5

Cox regression analysis of the need for rescue medication at 0–24 and 0–48 hours. P values represent comparisons of Q8003 vs morphine or oxycodone using the chi-square test.

Figure 6

Mean total dose of ibuprofen used as rescue medication.