385 - Naloxegol Compared with PEG 3350 in Patients with Opioid-Induced Constipation Related to Chronic Non-Cancer Pain Syndromes: An Open-Label, Phase IV, Crossover, Patient Preference Study

Background: Consensus guidelines for opioid-induced constipation (OIC) recommend overthe-counter (OTC) laxatives as first-line agents.These options are well-tolerated and readily available, but there is insufficient high-quality evidence to support their use.Furthermore, they do not specifically target the opioid receptor-mediated mechanism of OIC.Consensus recommendations also suggest that prescription treatments for OIC be considered for patients with a Bowel Function Index (BFI) score of $30 and an inadequate response to OTC laxatives.The purpose of this study (NCT03060512) was to determine patient preference for treating OIC with the peripherally acting mu-opioid receptor antagonist (PAMORA) naloxegol, approved for treating OIC in adults with chronic non-cancer pain, or the osmotic OTC laxative PEG 3350.Methods: This prospective, randomized, US-based, Phase IV, openlabel crossover study, which included two 2-week active treatment periods (with washout periods), enrolled patients who had baseline BFI scores $30, were receiving opioids for chronic non-cancer pain, and were willing to discontinue ongoing laxatives.The primary endpoint, patient preference, was measured at the end of the second treatment period with a 7-point scale (Table 1), which was collapsed into 3 categories: preferred naloxegol, no preference, and preferred PEG 3350.Additional outcome measures included changes in BFI and Patient Global Impression of Change (PGIC) scores at the end of each treatment phase.Adverse events were also recorded.Results: A total of 276 patients were randomized at 59 sites (per protocol population, n = 246).A similar proportion of patients reported preference for naloxegol (124/246 [50.4%]) and PEG 3350 (118/246 [48.0%];P = 0.92); 1.6% (4/ 246) reported no preference.A strong preference for either treatment was most commonly reported (Table 1).Medication characteristics influencing treatment preference were similar for both treatments, with the exception of convenience, which strongly influenced preference for 69.9% (86/123) of patients preferring naloxegol, but only 29.9% (35/117) of patients preferring PEG 3350 (Table 2).Overall treatment effects on BFI and PGIC scores (demonstrating clinical improvement) were similar, and safety profiles were consistent with known product profiles.Conclusion: Patients with OIC receiving opioids for chronic non-cancer pain demonstrated a dichotomy of strong preference after two 2-week active treatment periods, but no statistically significant differences between naloxegol and PEG 3350.Further exploration of patient characteristics may help to explain the dichotomy in patient preference.Overall, these results support consensus recommendations that naloxegol (a PAMORA) may be an effective and convenient option in patients with OIC with inadequate response to OTC laxatives.Table 1.Primary Endpoint -