MoxDuo IR study completion could yield primary pain relief end points

QRxPharma has announced a successful interim analysis of its final MoxDuo IR pivotal phase 3 study required for new drug application (NDA) submission.

QRxPharma has announced a successful interim analysis of its final MoxDuo IR pivotal phase 3 study required for new drug application (NDA) submission. MoxDuo IR is a patented, immediate-release oral formulation combining morphine and oxycodone intended for the acute management of moderate to severe pain. Upon approval, it will be the first opioid-opioid combination product in the United States or elsewhere.

The analysis indicated the planned sample size of 140 patients has greater than 90% power to detect differences of analgesic effect, indicating there is no need to enroll additional patients in this study that evaluates MoxDuo IR pain relief following total knee replacement (TKR) surgery. QRxPharma anticipates completing analysis of this study in the fourth quarter of 2010 and filing an NDA for MoxDuo IR in the first quarter of 2011.

“MoxDuo IR successfully met FDA requirements for combination rule products from our earlier pivotal phase 3 study, and with this pivotal study, we are well along the way to demonstrating significant pain relief in patients following total knee replacement,” John W. Holaday, PhD, managing director and CEO of QRxPharma told Formulary. “These interim results indicate the strong likelihood that when the study is completed . . . we will reach statistical significance.”

QRxPharma is currently completing its product registration clinical program for MoxDuo IR (a 3:2 ratio of morphine to oxycodone) in the management of moderate to severe acute pain. This comparative study conducted at 10 centers in the United States, now well over half-way complete, is evaluating analgesic efficacy and tolerability of a flexible dose regimen (12-mg morphine/8-mg oxycodone) versus a fixed low dose (3 mg/2 mg) of MoxDuo IR in 140 patients with moderate to severe pain following TKR surgery (patients on flexible dose receive approximately 12 mg/8 mg every 6 hours; this dose is achieved by titrating upward or downward in time and according to their pain level and tolerability).  In agreement with FDA, the fixed low dose of MoxDuo was chosen as the comparator in lieu of placebo to provide patients with some pain relief.

The study design included a blinded interim analysis (70 completed patients) to be conducted by an independent statistician for the purpose of sample size confirmation. This interim analysis indicated that the projected sample size of 140 patients is likely to provide sufficient power to distinguish the analgesic effects of flexible dose versus fixed low dose of MoxDuo IR over a 48-hour study period. Since the blinded interim analysis was based on how much variability was observed when both dosage groups were combined and did not evaluate the magnitude of the difference between the 2 treatment groups per se, one must be cautious in drawing conclusions that the expected end points will be met. This type of interim analysis was accepted by FDA for the purpose of sample size re-estimation.

“We further agreed with FDA that if we locked the data at the half-way point, and had a blinded statistician evaluate the variability between groups, there would be no statistical penalty as we took a ‘peek’ at interim data to consider whether we needed to add patients,” Holaday said. “It turned out to be the case that we probably don’t need to add patients to achieve statistical significance.”

“We now have successfully met primary end points in 5 phase 2 and 3 studies demonstrating that whether MoxDuo is administered in our acute IR oral formulation or our intravenous formulation, we observe better pain relief with about half the side effects as morphine, oxycodone, or Percocet in patients following bunionectomy, total knee replacement, or hip replacement surgeries,” Holaday said. “The ability to reduce the significant side effects of opioids has been sought as the ‘Holy Grail’ of opioid pharmacology for over 100 years, and we believe that MoxDuo may offer that promise.”