In response to the comments, the protocol has been amended and AcelRx plans to initiate the study in the first quarter of 2016. The IAP312 study will include approximately 310 post-operative patients and collect information requested by the Division to supplement the three positive Phase 3 trials already completed.
Zalviso is being developed for the management of moderate-to-severe acute pain in adult patients in the hospital setting.
AcelRx interim CEO Howie Rosen said: "Even though we’ve performed extensive bench and human factors testing to demonstrate the reliability and usability of Zalviso since our successful Phase 3 trials, we acknowledge the Division’s desire to see additional Zalviso use by patients in a clinical setting.
"We are pleased that we have a path forward in the U.S. that should lead to resubmission of the NDA."
The planned open-label Phase 3 study will enroll adult postoperative patients who will self-administer 15 mcg sublingual sufentanil using Zalviso for 24-to-72 hours.
Patients will self-administer study drug as often as once every 20 minutes to manage their moderate-to-severe acute pain. The study will measure the rate of device errors, including the failure to dispense medication as well as the incidence of misplaced or dropped tablets. Efficacy pain measurements and safety data will also be collected in the study.
The NDA resubmission will include, in addition to the results of bench testing and human factors studies conducted with the modified Zalviso design, the results from the IAP312 study.
Prior Phase 3 trials include two Phase 3 placebo-controlled studies (IAP310 and IAP311) in which Zalviso demonstrated superiority over placebo in the management of moderate-to-severe acute post-operative pain, as measured by time-weighted SPID48, the primary endpoint.
In IAP309, a Phase 3 active-controlled study, Zalviso was statistically significantly superior (p=0.007) in patient global assessment (PGA) of method of pain control in comparison to intravenous (IV) PCA morphine. The most common adverse events experienced by patients using Zalviso were nausea, pyrexia (fever) and vomiting.