A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PHASE III CLINICAL TRIAL OF THE SAFETY OF ALVIMOPAN (ALV) IN PATIENTS (pts) UNDERGOING TOTAL ABDOMINAL HYSTERECTOMY (TAH)

T.J. Herzog,¹ L. Techner,² W. Du,² B.A. Wallin,²

¹Columbia University, New York, NY and ²Adolor Corporation, Exton, PA

OBJECTIVE: Investigate the safety of ALV, a novel mu opioid receptor antagonist, in pts undergoing TAH.

MATERIALS AND METHODS:  519 women undergoing TAH were randomized (4:1) to ALV 12 mg or placebo (PLA) orally >2h before surgery, then BID in hospital/at home for a total of 7d. Time to events (first flatus, first bowel movement [BM], tolerating first solid food) were monitored while pts were in hospital, and pts recorded events in a diary at home for the remaining 7d treatment period. Safety data were monitored for up to 30d after the last dose. The safety population included all pts who received ALV/PLA and had any safety assessment. Efficacy was assessed in intent-to-treat pts who underwent the protocol-specified surgery and had any efficacy assessment. Differences in AE incidence were assessed using 2-sided Fisher’s exact tests. Differences in time to events during the 7d treatment period were expressed using Cox proportional hazard ratios (HR) and 95% CI and KM estimates of means. Time to events included a composite endpoints representing recovery of both upper and lower GI function (GI-3; which consisted of time to 1-first flatus or 2-first BM and 3-first toleration of solid food) and time to first BM.

RESULTS: Mean age was 44 years. The most common cause for surgery was uterine fibroids (50%). The most common treatment-emergent AEs (TEAEs) were nausea (PLA, 64.2%; ALV, 72.6%; P=0.075), vomiting (PLA, 25.5%; ALV, 31.5%; P=0.286), constipation (PLA, 31.1%; ALV, 23.0%; P=0.077) and flatulence (PLA, 18.9%; ALV, 18.4%; P=0.889). The proportion of pts with >1 TEAE (PLA, 94.3%; ALV, 96.1%) and AE-associated discontinuations (PLA, 4.7%; ALV, 3.9%) were similar between groups. Nausea and vomiting mostly occurred on day of surgery in both groups. Seven (6.6%) PLA pts vs 23 (5.6%) ALV pts reported serious AEs. Compared with PLA, ALV accelerated time to recovery by 1.9h for GI-3 (HR=1.163; CI: 0.93, 1.45; P=0.176) and by 22.2h for first BM (HR=2.326; CI: 1.84, 2.93; P<0.001).

CONCLUSIONS: ALV safety profile is similar to PLA in women undergoing TAH. ALV accelerated time to first BM.

Key Words: hysterectomy, postoperative ileus, gastrointestinal complications

Disclosure – Clinical Researchers: L. Techner, W. Du, B.A. Wallin, Adolor Corp.