QRxPharma initiates second pivotal phase III study of MoxDuo IR Dual-Opioid for NDA submission

QRxPharma Limited announced today initiation of its second pivotal Phase III registration trial (Study 009) to evaluate analgesic efficacy and safety of MoxDuo IR, a patented 3:2 ratio fixed dose combination of morphine plus oxycodone. This two-arm study will compare the effectiveness and safety of a flexible MoxDuo IR dose regimen to a fixed low dose for managing moderate to severe pain in patients who have undergone total knee replacement surgery. The Company expects to complete dosing in Q3 2010 in preparation for filing a New Drug Application (NDA) with the US Food and Drug Administration in Q4 2010. MoxDuo IR targets the acute pain market, a $2.5 billion segment of over $7 billion spent annually on prescription opioids in the US.

“In support of our Phase 3 program, clinical trials conducted to date have consistently demonstrated MoxDuo IR achieves as good or better pain relief with fewer incidences of moderate-severe side effects than morphine, oxycodone or Percocet. Based on these data, we are optimistic about the competitive advantages of MoxDuo,” said Dr. John Holaday, Managing Director and Chief Executive Officer, QRxPharma. “With the initiation of the Company’s second pivotal trial for MoxDuo IR, we are one step closer to definitively proving the value of our Dual-Opioid product to potential partners, prescribers and patients.”

In 2009, an open-label pilot study demonstrated improved analgesia of flexible dose MoxDuo IR (individual doses up to 24mg morphine/16mg oxycodone) compared to fixed, low dose MoxDuo IR (3mg morphine/2mg oxycodone) in patients with moderate to severe pain following total knee replacement surgery. Based on these results, low dose MoxDuo IR was selected as the control for this pivotal trial.

Study 009, a randomised, double blind trial, is targeted to enroll 140 patients (70 per study Arm) at 8 US clinical research sites. Initially, all post-operative patients will receive intravenous patient controlled analgesia (PCA) morphine until the day following knee replacement surgery. At such time, PCA morphine dosing will be stopped. When pain becomes moderate to severe [based on the 10-point Numerical Pain Rating Scale (NPRS)], patients will then be randomised in equal numbers to receive either a flexible regimen of MoxDuo IR (Arm 1) or the low dose control (Arm 2).

For patients assigned to the flexible dose regimen (Arm 1), the initial dose will be based on the Company’s proprietary algorithm (developed in the prior open label study) that converts PCA morphine to oral morphine equivalents of MoxDuo IR. All Arm 1 patients will start on at least 12mg/8mg (morphine/oxycodone); patients in Arm 2 will receive a loading dose of 6mg/4mg followed by 3mg/2mg regardless of their initial PCA dosing regimen. All patients will be dosed every four to six hours over a 48-hour period.

The primary endpoint for evaluating the efficacy of flexible dose versus low dose is the difference from baseline in pain intensity scores for each treatment group over the 48-hour treatment period [Sum of Pain Intensity Differences over 48 hours (SPID48) calculated using the 10-point NPRS]. Secondary endpoints include: (1) efficacy relating to the time to onset of analgesia and global assessment of effect (i.e. total pain relief) as well as amount of supplemental analgesia used throughout the treatment period; and (2) safety as measured by incidence and intensity of opioid-related adverse effects.

To date, more than 500 patients experiencing pain following different surgical procedures (bunionectomy and total knee replacement) as well as non-surgical patients with chronic pain have received MoxDuo IR. Study results consistently demonstrate MoxDuo IR’s greater overall tolerability allowing the doctors and patients to achieve as good or better pain relief with substantially fewer incidences of nausea, vomiting, constipation, dizziness, and hypotension. For example, at equal analgesic doses the frequency of moderate to severe adverse events was 50% to 75% lower among patients on MoxDuo IR than those receiving morphine, oxycodone or Percocet® (oxycodone plus acetaminophen).

In December, 2009, QRxPharma announced the initiation of its first Pivotal Phase 3 (combination rule) study in bunionectomy patients to demonstrate that MoxDuo IR provides superior analgesia compared to its component doses of morphine and oxycodone. According to the FDA, once these two pivotal studies are completed, 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 in Q3 2010 and file its NDA for MoxDuo IR by the end of year 2010.