Labopharm Inc announced the results of its recently completed North American phase-III clinical trial for its twice-daily formulation of tramadol and acetaminophen (study 06CCL3-001).
Study 06CCL3-001 was a multi-centre, randomized, double-blind, parallel-arm study that compared the efficacy and safety of Labopharm's twice-daily tramadol-acetaminophen formulation to placebo in the treatment of moderate to severe acute low back pain. A total of 277 patients were included in the study. Thirteen per cent of patients in the active treatment group discontinued early (12 per cent due to adverse events) and 5 per cent of patients in the placebo group discontinued early (2 per cent due to adverse events).
Results of the efficacy measures in the study demonstrated a statistically significant difference from placebo in some cases but not in others. An analysis of covariance demonstrated a statistically significant difference from placebo on the Sum of Pain Intensity Differences (SPID) over 50 hours using LOCF (last observation carried-forward) as the imputation method, however, the results were not statistically significant using LOCF/BOCF (baseline observation carried-forward), the primary endpoint.
A non-parametric analysis, however, demonstrated statistical significance using both LOCF and LOCF/BOCF as imputation methods. The difference from placebo on the Total Pain Relief (TOTPAR) score was also statistically significant using both LOCF and LOCF/BOCF imputation methods and the patients' global impression of the effectiveness of the study medication was statistically different from placebo. Statistical significance reflects a p-value of less than 0.05 in each of the analyses.
Regulatory authorities throughout the world have different requirements for the analysis and demonstration of efficacy in clinical trials. Labopharm believes that it is likely that the results of this trial are insufficient to support the acceptance of a New Drug Application (NDA) by the Food and Drug Administration (FDA) in the United States. The Company intends to discuss the matter with the FDA's Division of Anaesthesia, Analgesia & Rheumatology Products (DAARP) to determine the path forward. The results of this study are however statistically significant under analyses that the Company believes may be accepted for the evaluation of analgesics in Europe, Canada and other jurisdictions. Accordingly, the Company intends to meet with the regulatory authorities for these jurisdictions at the earliest available opportunity in pursuit of regulatory approval. Should the authorities be in agreement, the Company expects that it would submit a regulatory application in those jurisdictions.
Tramadol-acetaminophen products leverage the unique but complementary modes of action of each of the active ingredients to provide the analgesic strength of a mild opioid (tramadol) and the rapid pain relief of acetaminophen. Tramadol-acetaminophen combination products were first launched in 2001 in the United States and in 2003 in other major markets and are indicated for the short-term (five days or less) management of acute pain in the US and the symptomatic treatment of moderate to severe pain in the rest of the world.
Labopharm is an emerging leader in optimizing the performance of existing small molecule drugs using its proprietary controlled-release technologies.