The company expects to complete dosing in Q3, 2010, in preparation for filing a New Drug Application (NDA) with the FDA in Q4, 2010.
In 2009, an open-label pilot study demonstrated improved analgesia of flexible dose MoxDuoIR (individual doses up to 24mg morphine/16mg oxycodone) compared to fixed, low dose MoxDuoIR (3mg morphine/2mg oxycodone) in patients with moderate-to-severe pain, following total knee replacement surgery. Based on these results, low dose MoxDuoIR 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 eight 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 MoxDuoIR (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: efficacy relating to the time to onset of analgesia and global assessment of effect (ie total pain relief) as well as amount of supplemental analgesia used throughout the treatment period; and safety as measured by incidence and intensity of opioid-related adverse effects.
John Holaday, managing director and chief executive officer of QrxPharma, said: “In support of our Phase 3 program, clinical trials conducted to date have consistently demonstrated MoxDuoIR 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.
“With the initiation of the company’s second pivotal trial for MoxDuoIR, we are one step closer to definitively proving the value of our Dual-Opioid product to potential partners, prescribers and
patients.”