A randomized, double-blind comparison of OROS® hydromorphone and controlled-release morphine for the control of chronic cancer pain

<p>Abstract</p> <p>Background</p> <p>Long-acting opioid formulations are advocated for maintaining pain control in chronic cancer pain. OROS^®hydromorphone is a sustained-release formulation of hydromorphone that requires dosing once daily to maintain therapeutic concentrations. The objective of this study was to demonstrate the clinical equivalence of immediate-release and sustained-release formulations of hydromorphone and morphine for chronic cancer pain.</p> <p>Methods</p> <p>200 patients with cancer pain (requiring ≤ 540 mg/d of oral morphine) participated in this double-blind, parallel-group trial. Patients were randomized to receive hydromorphone or morphine (immediate-release for 2–9 days, sustained-release for 10–15 days). Efficacy was assessed with the Brief Pain Inventory (BPI), investigator and patient global evaluations, Eastern Cooperative Oncology Group performance status, and the Mini-Mental State Examination. The primary endpoint was the 'worst pain in the past 24 hours' item of the BPI, in both the immediate-release and sustained-release study phases, with treatments deemed equivalent if the 95% confidence intervals (CI) of the between-group differences at endpoint were between -1.5 and 1.5. No equivalence limits were defined for secondary endpoints.</p> <p>Results</p> <p>Least-squares mean differences (95% CI) between groups were 0.2 (-0.4, 0.9) in the immediate-release phase and -0.8 (-1.6, -0.01) in the sustained-release phase (intent-to-treat population), indicating that the immediate-release formulations met the pre-specified equivalence criteria, but that the lower limit of the 95% CI (-1.6) was outside the boundary (-1.5) for the sustained-release formulations. BPI 'pain now PM' was significantly lower with OROS^®hydromorphone compared with controlled-release morphine (least-squares mean difference [95% CI], -0.77 [-1.49, -0.05]; <it>p </it>= 0.0372). Scores for other secondary efficacy variables were similar between the two sustained-release treatments. At endpoint, > 70% of investigators and patients rated both treatments as good to excellent. The safety profiles of hydromorphone and morphine were similar and typical of opioid analgesics.</p> <p>Conclusion</p> <p>Equivalence was demonstrated for immediate-release formulations of hydromorphone and morphine, but not for the sustained-release formulations of OROS^®hydromorphone and controlled-release morphine. The direction of the mean difference between the treatments (-0.8) and the out-of-range lower limit of the 95% CI (-1.6) were in favor of OROS^®hydromorphone.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: NCT0041054</p

An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain

<p>Abstract</p> <p>Background</p> <p>Opioid analgesics have proven efficacy in the short-term management of chronic cancer pain, but data on their long-term use is more limited. OROS^®hydromorphone is a controlled-release formulation of oral hydromorphone that may be particularly well suited to long-term management of chronic cancer pain because it provides stable plasma concentrations and consistent analgesia with convenient once-daily dosing. The objective of this study (DO-118X) was to characterise the pain control achieved with long-term repeated dosing of OROS^®hydromorphone in patients with chronic cancer pain.</p> <p>Methods</p> <p>In this multicentre, phase III, open-label, single treatment, 1-year extension study, OROS^®hydromorphone was administered to 68 patients with moderate-to-severe chronic cancer pain, who had successfully completed a short-term equivalence study, and whose pain was controlled with a stable dose of medication (≥ 8 mg OROS^®hydromorphone or equivalent controlled-release morphine). Patients were started on the dose of OROS^®hydromorphone equivalent to the opioid dose on which they achieved dose-stable pain control in the equivalence study; dose adjustments were made as necessary and breakthrough pain medication was permitted. Efficacy was assessed with the Brief Pain Inventory (BPI) and patient and investigator global evaluations of treatment effectiveness. No formal statistical analysis was done.</p> <p>Results</p> <p>The mean (standard deviation) duration of exposure to study medication was 139 (129.9) days and the mean (standard deviation) average daily consumption of OROS^®hydromorphone was 43.7 (28.14) mg/day. All scores were maintained at a mild to moderate severity throughout the study; however, BPI scores for pain at its worst, pain at its least, pain on average, pain right now, and pain relief were slightly worsened at end point compared with baseline. Mean BPI pain interference with daily activities and patient and investigator global evaluation scores also remained generally stable. Treatment effectiveness was rated as fair to good throughout the study. The most frequently reported adverse events were nausea (n = 24, 35.3%), constipation (n = 22, 32.4%), and vomiting (n = 15, 22.1%).</p> <p>Conclusion</p> <p>The results of this extension study suggest that long-term repeated dosing with once-daily OROS^®hydromorphone can be beneficial in the continuing management of persistent, moderate-to-severe cancer pain.</p

Once-daily OROS® hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study-4

<p><b>Copyright information:</b></p><p>Taken from "Once-daily OROS® hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study"</p><p></p><p>International Journal of Clinical Practice 2007;61(10):1671-1676.</p><p>Published online Jan 2007</p><p>PMCID:PMC2040191.</p><p>© 2007 ALZA Corporation Journal compilation 2007 Blackwell Publishing Ltd</p

Comparison of BPI pain intensity ratings: end of previous opioid stabilisation phase vs

<p><b>Copyright information:</b></p><p>Taken from "Once-daily OROS® hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study"</p><p></p><p>International Journal of Clinical Practice 2007;61(10):1671-1676.</p><p>Published online Jan 2007</p><p>PMCID:PMC2040191.</p><p>© 2007 ALZA Corporation Journal compilation 2007 Blackwell Publishing Ltd</p> end of treatment. Scale: 0, no pain; 10, pain as bad as you can imagine (p ≤ 0.001 for all scores; no adjustment for multiple testing

Once-daily OROS® hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study-0

<p><b>Copyright information:</b></p><p>Taken from "Once-daily OROS® hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study"</p><p></p><p>International Journal of Clinical Practice 2007;61(10):1671-1676.</p><p>Published online Jan 2007</p><p>PMCID:PMC2040191.</p><p>© 2007 ALZA Corporation Journal compilation 2007 Blackwell Publishing Ltd</p

Comparison of BPI pain interference ratings: end of previous opioid stabilisation phase vs

<p><b>Copyright information:</b></p><p>Taken from "Once-daily OROS® hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study"</p><p></p><p>International Journal of Clinical Practice 2007;61(10):1671-1676.</p><p>Published online Jan 2007</p><p>PMCID:PMC2040191.</p><p>© 2007 ALZA Corporation Journal compilation 2007 Blackwell Publishing Ltd</p> end of treatment. Scale: 0, no interference; 10, complete interference (p < 0.001 for all scores; no adjustment for multiple testing