In addition to data from this Phase 3 orthopedic study, three other posters presented at both the EFIC meeting in Florence, Italy and the ASA in San Francisco highlight results from a Phase 3 placebo-controlled study conducted in abdominal surgery patients, a Phase 3 active-comparator study comparing Zalviso to intravenous patient-controlled analgesia (IV PCA) with morphine, and pharmacokinetic data from a study describing different routes of sufentanil delivery (IV vs. transmucosal vs. oral/swallowed), highlighting the clinical relevance of context-sensitive half-time (CST ½) and plasma:central nervous system equilibration half-life (t ½ke0) in selecting the appropriate opioid for treatment of acute pain.
Previously Reported Phase 3 Clinical Trial Results for Zalviso
At the end of September 2013, AcelRx submitted its NDA for Zalviso to the FDA for the management of moderate-to-severe acute pain in adult patients in the hospital setting. The filing is based the data from AcelRx's three Phase 3 clinical trials. Zalviso met the FDA-agreed primary endpoint in the two double-blind, placebo-controlled Phase 3 registration studies conducted in patients who had undergone major open-abdominal surgery or orthopedic surgery that involved either knee or hip replacement procedures. In each of these trials, patients treated with Zalviso to manage their post-surgical pain reported a rapid onset of pain relief. In addition, patients treated with Zalviso reported a greater SPID-48 compared to placebo-treated patients (p=0.001 and p<0.001, respectively). Adverse events reported across these two studies and considered possibly or probably related to treatment were generally mild-to-moderate in nature and similar for the majority of adverse events between Zalviso- and placebo-treated patients, with the exception of itching, which was significantly greater (p < 0.05) in the Zalviso-treated group.
The third Phase 3 study, an open-label, active-comparator trial comparing Zalviso to IV PCA with morphine demonstrated that Zalviso was non-inferior (p<0.001) and superior (p=0.007) to IV PCA morphine based on the primary endpoint of Patient Global Assessment of method of pain control comparison over the 48-hour trial period (PGA48) as determined by the combined percentage of patients with PGA ratings of "good" or "excellent". Secondary endpoints of summed pain intensity, summed pain relief, and dropouts due to inadequate analgesia over the 48-hour study period were similar between treatment groups. Zalviso-treated patients reported a significantly faster reduction in pain intensity compared to IV PCA morphine-treated patients in the first 4 hours of treatment. Fewer patients experienced oxygen desaturation events below 95% in the Zalviso-treated group compared to the IV PCA morphine-treated patients (p=0.028). In addition, both nurses and patients rated Zalviso significantly higher for Overall Satisfaction and Ease of Care compared to IV PCA with morphine. Overall, adverse events in the comparison trial were similar and most were mild-to-moderate in nature in both treatment groups.