Introduction: Linaclotide (LIN) is a guanylate cyclase-C agonist approved as an immediate-release (IR) formulation for irritable bowel syndrome with constipation (IBS-C). A LIN delayed-release (DR) formulation, DR1, was developed with the hypothesis that targeting the ileal region would increase abdominal pain relief and cause less fluid secretion. A Phase 2b dose-ranging study in IBS-C patients showed that a 300μg dose of LIN DR1 improved abdominal and bowel symptoms with an acceptable safety profile. This analysis aims to further examine symptom improvement in that study using responder radar plots, with a focus on LIN DR1 300μg (planned Phase 3 dose), LIN IR, and placebo (PBO). Methods: IBS-C patients meeting Rome III IBS criteria and baseline symptom requirements were randomized to 1 of 8 groups; this analysis includes the 199 patients in the PBO, LIN IR 290μg, and LIN DR1 300μg groups. Patients reported abdominal/bowel symptoms daily and adequate relief (yes/no) weekly during 2-week baseline (BL) and 12-week treatment periods. Change-from-BL and responder endpoints (abdominal pain [≥30% decrease from BL], CSBM+1 [increase of ≥1 complete spontaneous bowel movement from BL], APC+1 [both abdominal pain and CSBM+1 in the same week], and adequate relief, each for ≥6/12 weeks and ≥9/12 weeks) were analyzed. Results: Improvements from BL in abdominal pain, abdominal discomfort, spontaneous bowel movement (SBM) frequency, straining, and stool consistency were seen for DR1 vs PBO (nominal P<0.05); numerical improvements vs PBO were seen for other symptoms (Table). Changes from BL were generally similar in the DR1 and IR groups. 6/12 week responder rates were higher in DR1 vs PBO patients (nominal P<0.05) for APC+1, CSBM+1, and adequate relief; and numerically higher for abdominal pain (P=0.053; Figure). DR1 responder rates were numerically higher vs IR for APC+1, abdominal pain, and adequate relief, and similar for CSBM+1 (Figure). More stringent 9/12 week responder endpoints showed abdominal pain and adequate relief improvement for DR1 vs PBO (nominal P<0.05) and numerical improvement in abdominal pain vs IR (Figure). Diarrhea, the most common AE, led to discontinuation in 3%, 6%, and 0% of DR1, IR, and PBO patients, respectively.FigureTable: Table. Change from Baseline in Abdominal and Bowel SymptomsConclusion: Targeted LIN delivery with DR1 300μg appears to maintain constipation relief and may enhance benefit for abdominal pain and abdominal discomfort in IBS-C patients. Further study is warranted to confirm these results.