Assessment of analgesia in human chronic pain. Randomized double-blind crossover study of once daily Repro-Dose morphine versus MST Continus

Objective: This study evaluated Repro-Dose morphine (RDM; Reliadol from Nycomed Pharma), a new once daily controlled-release morphine formulation, against twice daily MST Continus (MST) at steady state in patients with chronic opioid responsive pain. Methods: A randomized double-blind two-way crossover design was used to evaluate the efficacy and adverse effects of RDM once daily or MST twice daily, at the same total daily doses, in patients with chronic stable pain (dose range 20–120 mg per day). During the RDM limb of the study active drug was administered in the evening and placebo in the morning. Dextromoramide was provided as escape analgesia throughout the study. Following a 5-day screening period, during which stability of oral opioid dose was verified, patients underwent two 5-day treatment periods, (one MST, one RDM) in random sequence. Pain scores, escape analgesia requirements and side-effects were compared using data from days 3, 4 and 5 of each treatment period. Any events or medication changes occurring during the study period thought liable to influence analgesia were regarded as protocol violations. Overall assessment and period preference was assessed by direct questioning. RDM treatment was regarded as successful if the amount of escape medication required during the RDM period was equal to or less than that required during the MST period. Results: Forty-seven patients were included in the study, of whom 40 completed both periods the intention to treat (ITT) population], 31 in strict accordance with the protocol the per protocol (PP) population]. Results were similar for both populations. There was no significant difference in pain scores or incidence of adverse events occurring during the MST and RDM periods. For the ITT population, requirements for escape medication during the RDM period were less than, equal to or greater than those recorded during the MST period for 14, 15, and 11 patients, respectively. Twenty-nine of 40 patients (72.5%) were therefore RDM treatment successes (95% confidence interval 56.1–85.4%). The percentage of patients preferring RDM (45%) combined with those with no preference (32.5%) was significantly higher than those preferring MST (22.5%; P = 0.0003). Conclusions: Oral morphine administered as RDM once daily is at least as effective and well tolerated as MST twice daily, with over 70% of patients in this double-blind crossover study reporting that RDM was equal or superior to MST. Received: 6 April 1998 / Accepted in revised form: 23 January 1999