Sustained safety and efficacy of once-daily hydromorphone extended-release (OROS® hydromorphone ER) compared with twice-daily oxycodone controlled-release over 52 weeks in patients with moderate to severe chronic noncancer pain.

Once-daily hydromorphone extended-release (OROS(®) hydromorphone ER) and oxycodone controlled-release (CR) are semisynthetic, ER opioid analgesics with established efficacy. An open-label, randomized, 24-week, parallel group, flexible-dose study demonstrated noninferiority of OROS hydromorphone ER vs. twice-daily oxycodone CR in patients with chronic noncancer pain. In total, 112 patients were enrolled in a 28-week, open-label extension study; 60 patients received OROS hydromorphone ER and 52 received oxycodone CR. The primary efficacy measure was the change from baseline to Weeks 38 and 52 in Brief Pain Inventory item "pain right now." Global assessments of efficacy, dosing convenience, and tolerability were secondary endpoints. Mean change in "pain right now" from baseline to Week 38 was -3.0 (OROS hydromorphone ER) vs. -2.8 (oxycodone CR), and from baseline to Week 52 was -2.9 vs. -2.8; these changes were similar to the changes in the core phase (-2.1 vs. -2.1). Similar improvements were demonstrated for secondary assessments, including pain, pain interference, and quality of life. At Week 52, global assessment of efficacy was rated as "very good" or "good" by the majority of patients (OROS hydromorphone ER, 91.7%; oxycodone CR, 86.5%). More patients in the OROS hydromorphone ER group (35.0% vs. 21.2%) assessed mode of drug intake as "very convenient." The majority of patients receiving OROS hydromorphone ER (88.3%) and oxycodone CR (88.5%) rated tolerability as "good" or "very good" at Week 52; few patients discontinued treatment because of an adverse event (1.6% vs. 0.4%, respectively). The effectiveness of OROS hydromorphone ER and oxycodone CR was maintained through 1 year.

A randomized study to demonstrate noninferiority of once-daily OROS(®) hydromorphone with twice-daily sustained-release oxycodone for moderate to severe chronic noncancer pain.

This was a randomized, open-label, comparative, parallel group study designed to demonstrate the noninferiority of once-daily OROS(®) hydromorphone compared with twice-daily sustained-release (SR) oxycodone in subjects with chronic noncancer pain severe enough to require continuous opioid therapy. The core phase (24 weeks) consisted of titration and maintenance periods. This was followed by an optional extension phase (28 weeks), which collected data used to assess long-term safety and efficacy outcomes. Five hundred four subjects were randomized between the 2 treatment groups. The primary efficacy analysis showed that OROS hydromorphone was noninferior to SR oxycodone (P = 0.011) as measured by change in Brief Pain Inventory (BPI) pain severity subscore "pain right now." The treatment difference with respect to change in BPI pain severity subscore "pain right now" was 0.29 (95% confidence interval: -0.27 to 0.84). The equianalgesic doses were 16 mg OROS hydromorphone and 40 mg SR oxycodone (median values). Secondary outcomes included other BPI scale items, the Medical Outcomes Study (MOS) Sleep Indices, and quality of life measured by the Short Form 36 (SF-36) questionnaire. Both treatment groups showed improvements in the main secondary efficacy endpoints. No statistically significant differences were shown between the treatment groups, except for the scores for somnolence (MOS sleep subscale) and physical functioning (SF-36), which both had a statistically significant difference between treatments groups in favor of OROS hydromorphone. Both study medications had equivalent and acceptable safety profiles. The results of this open-label study showed that once-daily OROS hydromorphone is a safe and well-tolerated treatment for chronic pain and as efficacious as twice-daily SR oxycodone.