OBJECTIVE: animal and human studies suggest that coadministration of two opioids with different receptor binding properties may result in enhanced analgesia and fewer opioid-related adverse events (AEs). Q8003 (MoxDuo), an oral dual-opioid formulation with a fixed ratio (3:2) of morphine and oxycodone, was evaluated for analgesic effects and safety in the management of acute moderate to severe pain. DESIGN: randomized, double-blind, placebo-controlled, ascending-dose cohort, dose-response study with flexible dosing. SETTING: private clinic. PATIENTS: adults undergoing unilateral bunionectomy surgery. Following surgery, patients were required to have moderate or severe intensity pain on a 4-point Likert scale and >or= 4 on an 11-point Numerical Pain Rating Scale to continue in the study. INTERVENTIONS: Q8003 was administered in four ascending-dose cohorts of 3/2, 6/4, 12/8, and 18/12 mg during the 48-hour period following surgery. MAIN OUTCOME MEASURES: sum of the pain intensity differences from baseline over 48 hours (SPID48), percentage of responders, and use of ibuprofen. RESULTS: Of 263 patients, 256 were randomly assigned to treatment. In patients treated with Q8003, 12 to 18 percent withdrew before study completion versus 30 percent on placebo. The mean dose of morphine/oxycodone per 6-hour period and the mean interdose interval (hours) was 6/4 mg (2.9), 9.8/6.5 mg (4.1), 11/7.5 mg (6.8), and 15/10 mg (6.6) for the 3/2-, 6/4-, 12/8-, and 18/12-mg groups, respectively. The mean SPID48 was significantly greater with each Q8003 dose when compared with placebo (p - 0.0017 for all doses versus placebo). The 12/8-mg group (11/7.5 mg/6 h) had the greatest percentage of patient responders (76 percent; p < 0.001 versus placebo) and required the fewest daily doses of ibuprofen. AEs were typical of those associated with opioid use, with the highest occurrence for nausea (38-65 percent) and low rates of somnolence (2-8 percent). Minimal or no changes in respiration and blood oxygenation were observed and euphoria was not reported. CONCLUSIONS: the 12/8 mg dose of Q8003, an immediate-release formulation, provided the optimal combination of analgesic efficacy and tolerability, with the 3/2 and the 6/4 mg doses being an effective alternative for treatment.
RCT Entities:
OBJECTIVE: animal and human studies suggest that coadministration of two opioids with different receptor binding properties may result in enhanced analgesia and fewer opioid-related adverse events (AEs). Q8003 (MoxDuo), an oral dual-opioid formulation with a fixed ratio (3:2) of morphine and oxycodone, was evaluated for analgesic effects and safety in the management of acute moderate to severe pain. DESIGN: randomized, double-blind, placebo-controlled, ascending-dose cohort, dose-response study with flexible dosing. SETTING: private clinic. PATIENTS: adults undergoing unilateral bunionectomy surgery. Following surgery, patients were required to have moderate or severe intensity pain on a 4-point Likert scale and >or= 4 on an 11-point Numerical Pain Rating Scale to continue in the study. INTERVENTIONS:Q8003 was administered in four ascending-dose cohorts of 3/2, 6/4, 12/8, and 18/12 mg during the 48-hour period following surgery. MAIN OUTCOME MEASURES: sum of the pain intensity differences from baseline over 48 hours (SPID48), percentage of responders, and use of ibuprofen. RESULTS: Of 263 patients, 256 were randomly assigned to treatment. In patients treated with Q8003, 12 to 18 percent withdrew before study completion versus 30 percent on placebo. The mean dose of morphine/oxycodone per 6-hour period and the mean interdose interval (hours) was 6/4 mg (2.9), 9.8/6.5 mg (4.1), 11/7.5 mg (6.8), and 15/10 mg (6.6) for the 3/2-, 6/4-, 12/8-, and 18/12-mg groups, respectively. The mean SPID48 was significantly greater with each Q8003 dose when compared with placebo (p - 0.0017 for all doses versus placebo). The 12/8-mg group (11/7.5 mg/6 h) had the greatest percentage of patient responders (76 percent; p < 0.001 versus placebo) and required the fewest daily doses of ibuprofen. AEs were typical of those associated with opioid use, with the highest occurrence for nausea (38-65 percent) and low rates of somnolence (2-8 percent). Minimal or no changes in respiration and blood oxygenation were observed and euphoria was not reported. CONCLUSIONS: the 12/8 mg dose of Q8003, an immediate-release formulation, provided the optimal combination of analgesic efficacy and tolerability, with the 3/2 and the 6/4 mg doses being an effective alternative for treatment.