Efficacy, Safety and Pharmacokinetic Study of a Novel Fentanyl-Containing Matrix Transdermal Patch System in Japanese Patients with Cancer Pain

Abstract

A novel transdermal matrix patch delivery system for fentanyl has been developed to deliver improved management of cancer pain compared with that obtained using current fentanyl reservoir patches. This study was carried out to assess the efficacy, safety and pharmacokinetic profiles of a 12.5 microg/h transdermal matrix fentanyl patch administered with the objective of replacing morphine, oral oxycodone or fentanyl injection formulations. The study also evaluated how the pharmacokinetic profiles of higher dose fentanyl patches (25, 37.5 and 50 microg/h) changed following dose adjustments to optimize management of cancer pain. This open-label, multicentre study involved 87 patients of both sexes (> or =20 years) with a confirmed diagnosis of cancer. Patients were receiving any one of the following at the time of enrollment for the management of their cancer pain: (a) morphine <45 mg/day orally, <30 mg/day as suppositories, or <15 mg/day by injection; (b) oral oxycodone <30 mg/day; or (c) fentanyl injectable preparations <0.3 mg/day. The patients were administered a 3-day course of fentanyl transdermal matrix patch application three times. The initial dose was 12.5 microg/h, which could be increased when a new patch was applied if the physician deemed this to be appropriate based on pain intensity ratings and use of rescue medications. Efficacy outcomes included patients' global assessment scores (primary efficacy endpoint) measured on a five-step scale and dichotomous scores for physicians' global assessment. The occurrence of adverse events and changes in laboratory tests were evaluated as safety variables. Serum fentanyl levels were measured immediately after removal of the old patch on days 4, 7 and 10 to obtain data on trough serum concentrations. The percentage of patients in category 3 or higher (very satisfied, satisfied, or neither satisfied nor dissatisfied) for the patient's global assessment score was 89.4% (76/85), indicating high patient satisfaction and attainment of sufficient pain control after patients switched from their previously used opioid analgesics. Similar findings were obtained on physicians' global assessment scores. A total of 316 adverse events occurred in 78 (90.7%) of 86 patients who were administered at least one patch. These included nausea (31 [36.0%]), somnolence (26 [30.2%]), vomiting (22 [25.6%]), diarrhoea (17 [19.8%]), constipation (14 [16.3%]), pyrexia (11 [12.8%]) and insomnia (9 [10.5%]). The mean (+/- SD) serum fentanyl concentration determined on day 4 was 169.9 +/- 103.4 pg/mL (n = 83). Serum fentanyl measurement results indicated that the same fentanyl patch dose resulted in similar serum fentanyl levels, while increased doses produced higher serum fentanyl concentrations. The fentanyl matrix transdermal patch formulation employed in this study demonstrated sufficient cancer pain control for patients switching from morphine or oral oxycodone preparations. The patch tested was well tolerated and its use did not result in any increased incidence of adverse drug reactions over those commonly found with opioid analgesics.