title: Efficacy of a new once daily hydromorphone formulation in comparison with twice daily administration in chronic pain: a randomized, double-blind, cross-over study.
abstract: Objective Efficacy and safety of a novel multiple-unit hydromorphone once daily (HOD) was compared to an established hydromorphone twice daily (HTD) regimen in patients with moderate-to-severe chronic pain. Design and methods The results from a randomized, double-blind, multicenter, cross-over trial in patients (n = 37) with chronic malignant or non-malignant pain are reported. The primary efficacy parameter was current pain on 0-100 mm VAS assessed four times daily and prior to intake of rescue medication (immediate-release hydromorphone) throughout the last 5 days with each treatment (after an 8 day build-up period to avoid carry-over effects). Total daily dose of hydromorphone (TDD: 8-32 mg/day) was kept stable during the double-blind treatment phase. Results The difference observed in mean current pain (-0.92 mm VAS) over the 5 day assessment period between HOD and HTD (28.44 mm vs. 29.36 mm VAS) was found to lack clinical relevance, as the 95% CI (-4.10 to 2.28 mm VAS) did not exceed the prespecified limit for non-inferiority of 9 mm VAS. Results from the full analysis set were consistent with per protocol data confirming robustness, as did the data for 12 h recalled pain assessed at 08:00 h and 20:00 h, showing no significant differences between once and twice daily medication. Both treatments produced effective and stable pain control with only minor day-to-day and intra-day fluctuations. Switching between treatments was suitable, considering both efficacy and safety, as no relevant or significant differences in adverse events were seen (25.0% HOD, 24.3% HTD). Most frequently typical side-effects of opioid therapy were observed, such as nausea, vomiting and headache. Conclusion Although this study was of short duration and included a limited number of patients, the results confirm that the new HOD is as effective and safe as the established HTD.
authors.affiliation: a Frankfurt am Main , Germany ;
authors.forename: Gudrun Edelgard
authors.initials: GE
authors.lastname: Nold
authors.affiliation: b Develco Pharma Schweiz AG , Pratteln , Switzerland ;
authors.forename: Martina Alice
authors.initials: MA
authors.lastname: Maritz
authors.affiliation: c Studienzentrum Dr. Schwittay , Böhlen , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schwittay
authors.affiliation: c Studienzentrum Dr. Schwittay , Böhlen , Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schumann
authors.affiliation: b Develco Pharma Schweiz AG , Pratteln , Switzerland ;
authors.forename: Hélène
authors.initials: H
authors.lastname: Rey
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D059350:Chronic Pain / Q000188:drug therapy*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010147:Pain Measurement
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004091:Hydromorphone
keywords: Chronic pain; Hydromorphone; New once daily prolonged-release tablet formulation; Non-inferiority