QRxPharma Limited announced the release of additional data on its phase III safety study for MoxDuo IR. Study 022 compared the respiratory effects of MoxDuo IR to equi-analgesic doses of either morphine or oxycodone in 375 patients experiencing moderate to severe postoperative pain following bunionectomy surgery at 4 US clinical research sites.
A more comprehensive statistical analysis has now been completed that highlights an important clinical advantage of MoxDuo with respect to respiratory depression. In study 022, respiratory impairment in these patient groups was measured by decreases in blood oxygen levels from the healthy normal range of 96-100% seen at baseline prior to the start of dosing. Oxygen values below 90% (a “desaturation” of haemoglobin) are usually considered clinically significant, and it is widely accepted that the greater the decline in blood oxygen saturation levels and the longer the desaturation lasts, the more severe the clinical outcome if no therapeutic intervention occurs.
To further evaluate such oxygen desaturation, the company analysed data from patients experiencing the worst (10th percentile) of all observed desaturations. The results demonstrated that the risk of the occurrence of such potentially dangerous desaturations was significantly greater in patients receiving morphine (p<0.009) or oxycodone (p<0.002) alone than in those receiving MoxDuo. Such desaturations occurred in 12% of the morphine, 15% of the oxycodone and 3% of the MoxDuo treated patients. These findings translate to a relative risk ratio of approximately 4:1 or 5:1 for the either morphine or oxycodone vs. MoxDuo.
“Respiratory depression is the leading cause of death from opioid treatment. Our breakthrough results indicate that MoxDuo provides a significant safety benefit with less clinical respiratory risk than either morphine or oxycodone.” said Dr John Holaday, managing director and CEO.
The company employed a state-of-the-art methodology for capturing the occurrences of oxygen desaturations – the primary study endpoint. Blood oxygen concentration was obtained electronically every 2 seconds from each patient over the 48 hr. study treatment period. This electronic recording process allowed for precise, quantifiable assessments of both the magnitude and duration of respiratory differences among patients receiving doses of MoxDuo, morphine or oxycodone.
“This superior respiratory safety profile for MoxDuo was shown in a study in which both young and old subjects participated,” said Holaday. “We believe that such results provide strong evidence to both regulatory agencies and the medical community that MoxDuo is a safer analgesic alternative.”
A more detailed analysis of Study 022 with respect to respiratory depression is provided in the attached supplement to this market release. It should also be noted that unlike earlier MoxDuo studies, Study 022 included a number of FDA-suggested study design elements to explore their utility in seeking one or more comparative label claims. One FDA recommendation required the administration of anti-nausea rescue medication only to patients that vomited and not to those only exhibiting nausea. This significantly limited the interpretation and comparative value of nausea and vomiting measurements and was not in keeping with normal clinical practice. Nonetheless, the occurrence rate of moderate to severe vomiting was significantly (p<0.04) reduced (32% vs. 42%) in MoxDuo IR treated subjects compared to patients receiving oxycodone alone at the same 24 mg morphine equivalent dose.
The Company remains on track to file its New Drug Application (NDA) for MoxDuo IR with the United States Food and Drug Administration (FDA) in August 2011. The European Marketing Authorisation Application (MAA) is scheduled for submission in the first half of 2012. MoxDuo is a patented 3:2 ratio fixed dose combination of morphine and oxycodone that targets the acute pain market, a $2+ billion segment of the $8 billion spent annually on prescription opioids in the US.
QRxPharma Limited is a clinical-stage specialty pharmaceutical company focused on the development and commercialisation of new treatments for pain management and Central Nervous System (CNS) disorders.