DURECT reports European POSIDUR Phase IIb hysterectomy clinical trial results

Jun 17 2010

DURECT Corporation (Nasdaq: DRRX) announced today results from a European Phase IIb hysterectomy clinical trial conducted by Nycomed of POSIDUR™ (also known as SABER™-bupivacaine or Optesia™ in the E.U.), a proprietary product under development for the treatment of post-surgical pain.

This hysterectomy trial is part of Nycomed's clinical development program for Europe for POSIDUR.  In this study, 115 patients were randomly assigned to one of three treatment groups prior to undergoing open hysterectomy surgery: POSIDUR at a dose of 5 mL, an active comparator (commercially available bupivacaine HCI solution) or SABER-Placebo (SABER vehicle without drug).  All patients were given a background pain treatment consisting of a daily dose of two or four grams (depending on the patient's weight) of paracetamol (acetaminophen).  In addition, each patient was provided supplemental opioid rescue medication, if needed.

With respect to efficacy, the primary endpoints of the study were to show (1) non-inferiority of POSIDUR to SABER-Placebo (with all groups taking the background and supplemental pain treatment as described above) in terms of pain intensity on movement area under the curve (AUC) during the period 1-72 hours post-surgery, and (2) superiority of POSIDUR against SABER-Placebo in the total use of opioid rescue analgesia 0-72 hours post-surgery.  Results from this study show that the first primary endpoint was met.  With respect to the second primary efficacy endpoint, no statistically significant difference was shown in opioid use between the POSIDUR and SABER-Placebo groups.  Secondary comparisons were performed towards the active comparator group with similar results.  In this study, patients in all treatment groups only took a meaningful amount of opioids during a shorter period of time after surgery than was expected.

In this study, there were no indications of systemic safety issues.  The plasma concentration profiles were consistent with previous studies, confirming the sustained release profile of the product.  Local observations (most commonly coded as post procedural haematomas) at the surgical site were observed with frequency in the POSIDUR and SABER-Placebo groups and not observed in the active comparator group.  These events were temporary and resolved without treatment.

"The data from this study further supports the CNS and cardiovascular safety profile of POSIDUR in another surgical model, but when few opioids are taken, it is difficult to show a reduction in opioid use," stated James E. Brown, President and CEO of DURECT Corporation.  "We are currently enrolling in BESST, our U.S. pivotal Phase III study and Nycomed continues to enroll in a Phase IIb study in Europe in shoulder surgery.  In addition, we had a recent FDA interaction which increased our confidence that the BESST design and overall NDA strategy, subject to data review from the entire POSIDUR development program, addresses the FDA's comments provided during past interactions regarding safety and evaluation of a diverse patient population that is likely to be exposed to the marketed product."