GSK and Adolor announce preliminary results from Phase 3 Safety study of Alvimopan (Entereg/Entrareg®)
London and Exton, PA, USA— GlaxoSmithKline (LSE and NYSE:GSK) and Adolor Corporation (Nasdaq:ADLR) today announced data from Study 767905/014 and provided an update on the clinical development program for alvimopan (Entereg/Entrareg®).
Study 014, a Phase 3, double blind, placebo-controlled (12 month) study, was designed to evaluate the long-term safety and tolerability of alvimopan 0.5 mg twice daily in patients taking opioids for chronic non-cancer pain and experiencing opioid-induced bowel dysfunction (OBD). A total of 805 patients were enrolled into the study and randomized 2:1; a total of 538 patients received alvimopan and 267 received placebo.
Consistent with findings from previous studies the most common adverse events observed in Study 014 were those affecting the gastrointestinal (GI) tract, including abdominal pain and diarrhea. The incidence of GI adverse events observed was similar between patients treated with alvimopan (40%) and placebo (35%).
While the proportion of patients experiencing serious adverse events was similar between those treated with alvimopan (13%) and placebo (11%), a numerical imbalance was observed in the number of cardiovascular (CV) and neoplasm cases categorized as serious adverse events among alvimopan-treated patients.
Preliminary findings from Study 014 are outlined below, together with information regarding actions taken by GSK and Adolor regarding the two ongoing alvimopan studies.
Cardiovascular Adverse Events
Results from a six-month interim analysis of Study 014, previously announced in November 2006, showed an increase which was not statistically significant in the reported incidence of serious CV adverse events in patients receiving alvimopan relative to placebo. Results from completed Study 014 showed an increase in myocardial infarctions and all CV SAEs reported by patients treated with alvimopan compared to placebo.
The CV SAEs reported in Study 014 occurred in patients with established or at high risk for CV disease. Five of seven myocardial infarctions occurred at two investigational sites. Additionally, the incidence of myocardial infarctions does not appear to be linked to the duration of dosing, with the majority of reported events in Study 014 occurring within the first 12 weeks of treatment.
Study 014 showed an imbalance in the incidence of neoplasms (benign, malignant, skin cancers and unspecified, including polyps), with 15 neoplasms reported in patients receiving alvimopan (2.8%) and 2 in patients receiving placebo (0.7%). Of these, 4 alvimopan (0.7%) and 1 placebo (0.4%)neoplasms were categorized as serious adverse events.
An increase in the incidence of fractures was also observed in patients receiving alvimopan relative to placebo. This data is in contrast to previously conducted studies that showed a similar or lower incidence of fractures in patients receiving alvimopan relative to placebo.
Preliminary Conclusions and Next Steps
As the findings outlined were observed during the preliminary evaluation of data from Study 014, and a full analysis has not yet been completed, further details are not yet available. Additional data are being collected and further analyses, which will include all alvimopan OBD studies, will be undertaken as soon as possible to better understand these findings.
Pending completion of these analyses, the protocol for an additional Phase 3 safety and efficacy study in patients with OBD (Study 015), which had been submitted to regulatory authorities, is being withdrawn by GSK.
As a precautionary measure, GSK has taken the decision to stop Study 101684, an extension of Study 008 in a cancer pain population, which currently has 15 patients receiving treatment. Clinical investigators involved in this study have been informed.
"Patient well-being is always our primary concern. These unexpected findings are not yet fully understood and require further analyses to ascertain the significance of the data. We are working to gain a better understanding of these findings, which will help guide our future development”, said Yvonne Greenstreet, Senior Vice President, Research and Development, GlaxoSmithKline.
Adolor has also suspended enrollment in Study 228 in rotator cuff surgery patients, a co-administration study being conducted as part of Adolor’s Combination Product Development Program, until a more complete understanding of these data are available. Clinical investigators involved in this study have been informed. Study 228 investigators have also been informed. GSK and Adolor currently have no other ongoing studies with alvimopan.
“We continue to believe in the clinical benefit of Entereg and look forward to the further analyses of these preliminary Study 014 results,” said Michael R. Dougherty, President and Chief Executive Officer of Adolor. “We are committed to working with GSK to provide an update on further clinical development plans in the opioid-induced bowel dysfunction program as soon as is possible. With regard to the POI program, we continue to target the second quarter of 2007 to submit to the FDA a Complete Response to the November 2006 approvable letter.”
About Adolor Corporation
Adolor Corporation (Nasdaq:ADLR) is a biopharmaceutical company specializing in the discovery, development and commercialization of novel prescription pain management products. Entereg® (alvimopan) is Adolor’s lead product candidate under development for the management of the gastrointestinal side effects associated with opioid use. Adolor and GlaxoSmithKline (GSK) are collaborating in the worldwide development and commercialization of Entereg® in multiple indications. Adolor also has a number of discovery research programs focused on the identification of novel compounds for the treatment of pain. By applying its knowledge and expertise in pain management, along with ingenuity, Adolor is seeking to make a positive difference for patients, caregivers and the medical community. For more information, visit www.adolor.com.
GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline on the World Wide Web at www.gsk.com.
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