Award: Presidential Poster Award
Darren M. Brenner, MD1, Howard Franklin, MD, MBA2, Gregory S. Sayuk, MD, MPH3
1Northwestern University Feinberg School of Medicine, Chicago, IL; 2Salix Pharmaceuticals, Bridgewater, NJ; 3Washington University School of Medicine and St. Louis VA Medical Center, St. Louis, MO
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 3mg and 6mg 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 (3mg, 4.6%; 6mg, 5.1%; placebo, 1.3%). Discontinuation rates due to AEs were 4.1% (3mg), 4.5% (6mg), and 2.2% (placebo), with low discontinuation due to diarrhea (3mg, 1.9%; 6mg, 1.8%; placebo, 0.4%).
Discussion: 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.
Citation: Darren M. Brenner, MD; Howard Franklin, MD, MBA; Gregory S. Sayuk, MD, MPH. P0341 - 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. Program No. P0341. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.