Combination Rule Study to Compare Analgesic Efficacy and Safety of MoxDuo(TM)IR with Oxycodone and with Morphine in Patients with Post-Surgical Pain
QRxPharma Limited (ASX: QRX and OTCQX: QRXPY) announced today, as part of its Phase 3 program, the initiation of a registration (also called pivotal) trial (Study 008) comparing efficacy and safety profiles of MoxDuo(TM)IR against component doses of morphine and oxycodone alone for the management of moderate to severe post-operative pain following bunionectomy surgery. The Company expects to complete dosing by close of Q2 2010.
"We recently reported clinical studies demonstrating the superiority of MoxDuo(TM)IR in terms of tolerability compared to equi-analgesic doses of morphine, oxycodone and Percocet(R) for the management of acute post-operative pain. These studies demonstrated that MoxDuo(TM)IR provides significant pain relief and fewer side effects (nausea, vomiting, dizziness and constipation)," said Dr. John Holaday, Managing Director and Chief Executive Officer, QRxPharma. "We are now addressing a regulatory requirement for New Drug Application (NDA) approval of MoxDuo(TM)IR, i.e., demonstration that it is superior in efficacy to its individual components."
A double-blind study with about 35 patients per group, completed earlier this year in patients with pain following bunionectomy surgery, demonstrated the superiority of MoxDuo 12 mg/8 mg relative to 12 mg morphine and to 8 mg oxycodone. The purpose of the current Phase 3 registration study (008) is to replicate these differences in a larger trial, one with sufficient statistical power to achieve significance on the primary and secondary endpoints. If successful, this trial will satisfy the "Combination Rule" requirement of the US Food and Drug Administration (FDA) and will also serve as a registration study.
This double-blind, randomized and repeat fixed-dose study compares MoxDuo(TM)IR's reduction in pain intensity (primary endpoint) to component doses of oxycodone and morphine in patients experiencing moderate to severe post-operative pain over 48 hours. The study is targeted to enroll 522 patients (with 174 in each treatment group) at 6 US clinical research sites.
The primary endpoint for evaluating the efficacy of MoxDuo(TM)IR 12 mg/8 mg versus its milligram components of morphine 12 mg and oxycodone 8 mg administered every six hours is the difference in pain intensity scores for each patient group over the 48-hour treatment period (SPID48 calculated from the 10-point Numerical Pain Rating Scale). Secondary endpoints include: (1) efficacy relating the patient's global assessment of effect (i.e. extent of overall pain relief) as well as amount of supplemental analgesia (acetaminophen) used throughout the treatment period; and (2) safety as measured by incidence and intensity of opioid-related adverse effects. QRxPharma incorporated input from the FDA regarding the design and statistical analysis of this study.
The final Phase 3 registration trial (Study 009: a double-blind controlled study to evaluate the effectiveness of MoxDuo(TM)IR in patients following total knee replacement surgery) is scheduled to begin Q1 2010. No additional pharmacology, toxicology or long-term clinical safety studies will be required for regulatory submission and market approval. QRxPharma expects to complete its Phase 3 program Q3 2010 and file its NDA for MoxDuo(TM)IR by EOY 2010.