Oxymorphone extended release for the treatment of chronic low back pain: A retrospective pooled analysis of enriched-enrollment clinical trial data stratified according to age, sex, and prior opioid use

Abstract

Objective: This study assessed the potential effects of age, sex, and prior opioid use on the response to oxymorphone extended release (ER) in patients with moderate to severe chronic low back pain. Methods: Combined data from 2 placebo-controlled clinical trials with an enriched-enrollment, randomized-withdrawal design were analyzed. In patients aged ≥18 years with chronic low back pain, the dose of oxymorphone ER was titrated to a stable, tolerable, effective dose. Patients who completed titration were randomly assigned to a 12-week double-blind study period with oxymorphone ER or placebo. Oxymorphone immediate release 5 mg was permitted q4-6h, as needed for rescue medication or withdrawal symptoms, for 4 days after randomization and restricted to 10 mg/d thereafter. Pain intensity (100-mm visual analog scale [VAS]; 0 = no pain to 100 = worst pain imaginable) and time to study discontinuation due to lack of efficacy were compared with stratification by age (<65 vs ≥65 years), sex, and prior opioid use. Adverse events were categorized by severity and relation to study medication. Results: Of 575 patients, 348 completed titration and 347 entered the double-blind study phase. There were no significant between-group differences in demographic variables, except that the mean age in the oxymorphone ER group was significantly higher ( P = 0.04), and the proportion of men was significantly lower ( P = 0.01). There was no significant age difference between the oxymorphone ER and placebo groups stratified by age (<65 vs ≥65 years). Fewer patients aged ≥65 years versus <65 years completed titration (45.0% [36/80] vs 63.0% [312/495]; P = 0.002). The least-squares mean (SEM) differences in VAS pain scores between the oxymorphone ER (n = 174) and placebo (n = 169) groups were significant at each postbaseline assessment ( P < 0.001) and at study completion (12.3 [2.8] mm; P < 0.001) and was not significantly affected by age, sex, or prior opioid use. Age and sex had no significant influence on adverse events or discontinuations due to lack of efficacy. More discontinuations due to lack of efficacy occurred among patients in the placebo group (hazard ratio, 5.01; P < 0.001) and among opioid-experienced patients. The latter effect was limited to opioid-experienced patients who received placebo. The rates of discontinuation due to lack of efficacy were similar between oxymorphone ER-treated opioid-naive and opioid-experienced patients (11.4% vs 11.6%). The proportion of patients who experienced opioid-related adverse events was significantly greater in the oxymorphone ER group compared with the placebo group (25.7% vs 16.3%; P = 0.03). The most frequent treatment-emergent adverse events in the oxymorphone ER group were nausea (8.0%), constipation (6.3%), vomiting (4.6%), and diarrhea (4.0%); in the placebo group were nausea (5.8%), diarrhea (4.7%), and increased sweating (2.3%). Conclusion: In the enriched population of patients who successfully titrated to oxymorphone ER, oxymorphone ER was effective and generally well tolerated, independent of patients' age, sex, or previous opioid use.