Rauck R et al. – OROS hydromorphone extended–release (ER) failed to achieve statistical significance for the primary endpoint using the prespecified imputation method (BOCF), likely due to the high discontinuation rate associated with the fixed–dose design. When data were analyzed according to an alternate method of imputation (LOCF), OROS hydromorphone ER demonstrated statistically significant improvements in pain, stiffness, and physical function.Methods
- This was a randomized, placebo–controlled, double–blind, fixed–dose study.
- Patients received placebo or fixed–dose OROS hydromorphone ER (8 or 16 mg).
- The primary efficacy measure was pain intensity score (11–point Numeric Rating Scale) at Maintenance Week 12, analyzed with baseline observation carried forward (BOCF) imputation for missing data.
- This study did not meet the primary efficacy measure using the BOCF imputation.
- Study discontinuation was high (52%).
- When analyzed using last observation carried forward (LOCF) imputation, the prespecified alternate method, OROS hydromorphone ER 16 mg provided significantly better analgesia than placebo (P = 0.0009).
- Treatment was associated with significant improvements in patient global assessment (P = 0.01), the overall Western Ontario and McMaster Osteoarthritis Index (WOMAC) (P = 0.0003), and its subscales: pain (P = 0.0001), stiffness (P = 0.0023), and physical function (P = 0.0006).
- Gastrointestinal adverse events, such as constipation and nausea, were common among patients receiving OROS hydromorphone ER.