Another secondary efficacy measure was a global assessment of overall treatment effectiveness completed by both the patient and the investigator separately. This was measured on a 5-point scale (1 = poor, 2 = fair, 3 = good, 4 = very good,

5 = excellent). No formal statistical testing was done on the data; only summary statistics were produced. For baseline Inhibitors,research,lifescience,medical and each of the 12 monthly visits, absolute observed values were used; whereas end point was calculated using the last observation carried forward (LOCF) method. Safety measures included monitoring of AEs, early discontinuations, concomitant medications, and physical examination findings. GCP standards were followed to record all AEs occurring during the study regardless of whether they were considered to be related to the study drug. Formal definitions of AEs and questionnaires were not used. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) classification. Inhibitors,research,lifescience,medical Safety data were summarised descriptively.

Results Study population 68 patients were Inhibitors,research,lifescience,medical enrolled into the study (Belgium, n = 14; Canada, n = 7; France, n = 2; Germany, n = 2; Netherlands, n = 22; Spain, n = 7; UK, n = 14). 35 patients had been taking OROS® hydromorphone and 33 had been taking CR morphine sulphate in the previous equivalence study. 10 patients (14.7%) completed the 1-year study, 4 patients (11.4%) who had previously been taking OROS® hydromorphone and 6 patients (18.2%) who had been taking CR morphine. The reasons for not completing the study

are shown in Table ​Table2;2; Inhibitors,research,lifescience,medical the most common reasons for not completing were death (22.1% of patients) and progression of disease (20.6%). Only a small proportion discontinued owing to lack of efficacy (11.8%). The rate and reasons for the dropouts did not appear to be related to prior therapy. The baseline demographics and clinical characteristics of the study population were similar between patients who had taken the two previous treatments (Table ​(Table33). Inhibitors,research,lifescience,medical Table 2 Patient disposition (overall and by previous treatment) Table 3 Baseline demographic and clinical characteristics until (overall and by previous treatment) Extent of exposure to study medication During the study, for all patients, the mean (standard deviation [SD]) PKA inhibitor duration of exposure to study medication was 139 (129.9) days (range, 2.0 to 438 days). The mean (SD) average daily consumption of OROS® hydromorphone was 43.7 (28.14) mg/day (range, 9.6 to 139.2 mg/day). Each of these variables was slightly higher in patients who received morphine in the previous study. At the beginning of the study, 8 patients received doses of ≥ 64 mg (64 mg, n = 1; 72 mg, n = 4; 96 mg, n = 3); at end point, this increased to 20 patients (64 mg, n = 2; 72 mg, n = 4; 80 mg, n = 3; 96 mg, n = 6; and n = 1 each for 112, 128, 168, 176, and 192 mg).