This open-label, phase 3b study (ClinicalTrials.gov Identifier: NCT00983073) evaluated the effectiveness, and tolerability of
tapentadol for severe, chronic
osteoarthritis knee pain that was inadequately managed with World Health Organization (WHO) Step I or II
analgesics or co-
analgesics, or that was not treated with regular
analgesics. Prior to starting study treatment, patients discontinued any WHO Step II
analgesics, while Step I
analgesics and/or co-
analgesics were continued at the same dose. Patients received
tapentadol prolonged release (50-250 mg bid) during a 5-week titration period and a 7-week maintenance period. Doses of
tapentadol immediate release 50 mg (≤twice/day; ≥4 hours apart) were permitted throughout the study (total daily dose of
tapentadol prolonged and immediate release, ≤250 mg bid). The primary endpoint was the change in
pain intensity on an 11-point numerical rating scale-3 (NRS-3; recalled average
pain intensity [11-point NRS] during the last 3 days) from baseline to Week 6, using the last observation carried forward (LOCF) to impute missing
pain intensity scores. The mean (standard deviation) change from baseline to Week 6 (LOCF) in
pain intensity was -3.4 (2.10; P < 0.0001) for all patients evaluated for effectiveness (n = 195). Significant decreases in
pain intensity were also observed at Weeks 6, 8, and 12 (all P < 0.0001) using observed-case analysis. Corresponding significant improvements from baseline to Weeks 6 and 12 were observed in the Western Ontario and McMaster Universities
osteoarthritis index, the EuroQol-5 Dimension health status questionnaire, the Short Form-36 health survey, and the Hospital Anxiety and Depression Scale (all P ≤ 0.0103). Treatment-emergent adverse events were in line with those observed in previous studies of
tapentadol prolonged release. Overall, the results of this study indicate that
tapentadol treatment results in significant improvements in
pain intensity, health-related quality of life, and function in patients with inadequately managed, severe, chronic
osteoarthritis knee pain.