Dose Conversion and Titration with a Novel, Once-Daily, OROS® Osmotic Technology, Extended-Release Hydromorphone Formulation in the Treatment of Chronic Malignant or Nonmalignant Pain

Abstract The objective of this open-label, repeated-dose, single-treatment, multicenter study was to evaluate the outcomes associated with a standardized conversion from prior opioid therapy to a novel, once-daily, OROS ® osmotic technology, extended-release (ER) hydromorphone formulation in an outpatient population with chronic malignant or nonmalignant pain. The study period was divided into 3 phases: the prior opioid stabilization phase (≥3 days), the conversion and titration phase (3–21 days), and the maintenance phase (14 days). Patients were evaluated at 5 visits during the study period. Analgesic efficacy was measured using the Brief Pain Inventory (BPI). At baseline, patients were required to have daily oral morphine equivalent requirements of ≥45 mg. Prior oral or transdermal opioid therapy was converted to single daily doses of ER hydromorphone (8, 16, 32, and 64 mg tablets) at a 5:1 (morphine equivalent to hydromorphone) ratio. Immediate-release (IR) hydromorphone was given as rescue medication for breakthrough pain. Among the 445 patients who enrolled, 404 received the study medication. Of these, 73 (18.1%) had chronic malignant pain and 331 (81.9%) had chronic nonmalignant pain. Dose stabilization (defined as a 3-day period during which the total daily dose of ER hydromorphone remained unchanged and ≤3 doses of IR hydromorphone per day were required) was attained by 73.8% of patients (298/404), of whom 70.1% (209/298) were stabilized with ≤2 titration steps. The mean ± standard deviation (SD) time to dose stabilization was 12.1 ± 5.7 days (range of 3 to 33 days). The mean ± SD final daily dose of ER hydromorphone was 63.4 ± 129.2 mg. The mean ± SD final daily dose of IR hydromorphone was 11.5 ± 36.4 mg, and the mean ± SD final number of daily doses of IR hydromorphone was 1.7 ± 1.3. Intent-to-treat and completer analysis demonstrated significant improvements in BPI ratings from prior opioid therapy to the end of ER hydromorphone therapy (P