472 Impact of Plecanatide on Symptoms and Quality of Life for Patients With Chronic Idiopathic Constipation: Analysis of PAC-SYM and PAC-QOL From Two Phase III Clinical Trials

Abstract

INTRODUCTION: Plecanatide, a 16-amino acid analog of human uroguanylin, activates guanylate cyclase-C receptors in the small intestine in a pH-sensitive manner to induce fluid secretion and peristalsis. This analysis looks at whether plecanatide improved global symptoms and health-related quality of life (HRQOL) in patients with chronic idiopathic constipation (CIC) from 2 large-scale, randomized, double-blind, placebo-controlled, phase 3 studies. METHODS: Patients (N = 2683) who met modified Rome III criteria were randomized to placebo, plecanatide 3mg, or 6mg QD for 12 weeks and included in the phase 3 intention-to-treat populations. Baseline characteristics were comparable between groups and across studies. CIC symptoms and HRQOL were evaluated using the Patient Assessment of Constipation–Symptoms (PAC-SYM) and Patient Assessment of Constipation–Quality of Life (PAC-QOL) scales, respectively. The PAC-SYM measured patients' constipation symptom experience and severity over time, including abdominal, rectal, and stool symptoms of constipation. The PAC-QOL evaluated patients' HRQOL perceptions with constipation and rated patients' worries and concerns, physical discomfort, psychosocial discomfort, satisfaction, and overall effects on HRQOL. Scales were rated from 0 to 4 with reductions in scores indicating improvement. Efficacy analyses evaluated each plecanatide dose vs placebo. RESULTS: Statistically and clinically significant improvements in PAC-SYM (∼ −0.75-point changes; Table 1) and PAC-QOL (∼ −1.0-point change; Table 2) were observed at Weeks 4, 8, and 12 for both plecanatide 3 mg and 6 mg vs placebo across both studies. Plecanatide-treated patients reported significant improvements vs placebo in all PAC-SYM domain scores, except in Study 2 for abdominal symptoms. Significant improvements in plecanatide arms vs placebo were seen in 3 of 4 PAC-QOL domain scores (worries and concerns, physical discomfort, satisfaction). The most common adverse event (AE) was diarrhea (3 mg, 4.6%; 6 mg, 5.1%; placebo, 1.3%). Discontinuation rates due to AEs were 4.1% (3 mg), 4.5% (6 mg), and 2.2% (placebo), with low discontinuation due to diarrhea (3 mg, 1.9%; 6 mg, 1.8%; placebo, 0.4%). CONCLUSION: Patients who received plecanatide 3mg and 6mg had statistically and clinically significant improvements in global constipation symptoms and HRQOL at all measured time points. Plecanatide treatment was associated with a low incidence of AEs and was well tolerated.