Opioids in non-cancer pain: Efficacy and safety of 24-hour hydromorphone hydrochloride extended-release compared with placebo in patients with nonmalignant pain

Abstract

Hydromorphone hydrochloride extended-release (HHER) is a q24h formulation for the treatment of persistent moderate to severe pain. On FDA approval, HHER will be marketed as PalladoneTM Capsules. This randomized, double-blind, parallel-group, placebo-controlled study assessed the efficacy and safety of HHER compared with placebo in patients with persistent nonmalignant pain. Patients taking the equivalent of ≤60 mg of oxycodone per day were eligible. Patients took HHER 12 mg or placebo q24h for 28±2 days. The primary efficacy variable was the time from first dose of HHER or placebo to emergence of inadequate analgesia. Secondary efficacy variables were the subject global assessment of pain medication (1=poor to 5=excellent) and the pain control questionnaire (0=usually poor to 3=usually effective around-the-clock). A 6-symptom withdrawal rating scale was used to assess whether withdrawal symptoms confounded pain assessments in the placebo group. Safety was assessed by adverse events, vital signs, clinical laboratory tests, and physical examination. A total of 212 patients completed the study. Time to emergence of inadequate analgesia (Kaplan-Meier estimator) was longer for HHER compared with placebo (P<.0001; log-rank test); median, >28 and 4 days, respectively. Mean subject global assessment of pain medication was higher for HHER than placebo (P<.0001; ANOVA); 2.6±0.13 (±SEM) and 1.8±0.11, respectively. Mean pain control questionnaire rating was higher for HHER than placebo (P<.0001; ANOVA); 1.5±0.1 and 0.7±0.1, respectively. Mean sum of the opioid withdrawal ratings was not different between groups (P=.621; 2-sided t test). No clinically important changes in laboratory values or vital signs occurred. These results indicated that time to emergence of inadequate analgesia was significantly longer in HHER-treated patients than with placebo. Both secondary efficacy variables indicated that HHER is effective in treating persistent pain. Opioid withdrawal did not appear to confound the results of the primary end point. No unexpected safety concerns were identified. Hydromorphone hydrochloride extended-release (HHER) is a q24h formulation for the treatment of persistent moderate to severe pain. On FDA approval, HHER will be marketed as PalladoneTM Capsules. This randomized, double-blind, parallel-group, placebo-controlled study assessed the efficacy and safety of HHER compared with placebo in patients with persistent nonmalignant pain. Patients taking the equivalent of ≤60 mg of oxycodone per day were eligible. Patients took HHER 12 mg or placebo q24h for 28±2 days. The primary efficacy variable was the time from first dose of HHER or placebo to emergence of inadequate analgesia. Secondary efficacy variables were the subject global assessment of pain medication (1=poor to 5=excellent) and the pain control questionnaire (0=usually poor to 3=usually effective around-the-clock). A 6-symptom withdrawal rating scale was used to assess whether withdrawal symptoms confounded pain assessments in the placebo group. Safety was assessed by adverse events, vital signs, clinical laboratory tests, and physical examination. A total of 212 patients completed the study. Time to emergence of inadequate analgesia (Kaplan-Meier estimator) was longer for HHER compared with placebo (P<.0001; log-rank test); median, >28 and 4 days, respectively. Mean subject global assessment of pain medication was higher for HHER than placebo (P<.0001; ANOVA); 2.6±0.13 (±SEM) and 1.8±0.11, respectively. Mean pain control questionnaire rating was higher for HHER than placebo (P<.0001; ANOVA); 1.5±0.1 and 0.7±0.1, respectively. Mean sum of the opioid withdrawal ratings was not different between groups (P=.621; 2-sided t test). No clinically important changes in laboratory values or vital signs occurred. These results indicated that time to emergence of inadequate analgesia was significantly longer in HHER-treated patients than with placebo. Both secondary efficacy variables indicated that HHER is effective in treating persistent pain. Opioid withdrawal did not appear to confound the results of the primary end point. No unexpected safety concerns were identified.