Analgesic efficacy and tolerability of tramadol 100mg sustained-release capsules in patients with moderate to severe chronic low back pain

Objective: To investigate the analgesic efficacy, tolerability and therapeutic equivalence of a newly developed tramadol sustained-release (SR) capsule compared with a tramadol immediate-release (IR) capsule in patients with moderate to severe chronic low back pain. Design: Randomised, multicentre, double-blind, parallel-group study. Setting: Patients were provided with a diary card into which they recorded by use of a visual analogue scale (VAS) the intensity of pain immediately before every intake of study medication during the 9 treatment days. Besides pain intensity, secondary efficacy parameters included a sleep questionnaire, a functional capacity score and the patient's global assessment of efficacy. Patients: 247 patients of either gender, aged 18 to 75 years, with moderate to severe chronic low back pain were included in the study. Interventions: 125 patients were treated with tramadol SR capsules twice daily (2 x 100 mg/day) and 122 patients with tramadol IR capsules 4 times daily (4 x 50 mg/day) over a period of 9 (+3) days. Results: The mean (+/-SD) baseline pain intensity values on the 100mm VAS scale were 55.6mm (+/- 10.6mm) and 53.3mm (+/- 10.6mm) in the IR group and the SR group, respectively. The mean baseline VAS value decreased substantially in both treatment groups during the first 2 days and decreased continuously throughout the treatment period. At treatment day 8, the mean difference to baseline VAS value for tramadol IR was -24.7 (+/- 20.1) mm and for tramadol SR -25.1 (+/- 19.9)mm. The corresponding 90% confidence interval was calculated as [-4.18; +5.09]mm, which fell completely within the predefined equivalence range of +10mm VAS. The two I-sided t-test method showed strong evidence for the equivalence of treatment groups (p < 0.001) regarding the VAS pain assessment. The secondary efficacy parameters also confirmed the therapeutic equivalence of the two formulations. The predominant adverse events, headache and nausea, were reported more frequently by patients treated with tramadol IR. With the IR formulation the incidence of headache and nausea was 29 and 21%, respectively, compared with 18 and 11% with the SR formulation. For the symptom nausea, the difference was statistically significant (p = 0.03). There were no clinically relevant changes in vital signs or laboratory parameters in either treatment group. Conclusions: The results confirmed therapeutic equivalence of tramadol SR 100mg capsules twice daily and tramadol IR 50mg capsules four times daily. At the same time the study demonstrated that tramadol provides adequate pain relief in patients with chronic low back pain. Moreover, tramadol administered as sustained-release capsules was better tolerated than the reference product.