Award: Presidential Poster Award
Darren Brenner, MD
Northwestern University Feinberg School of Medicine
Chicago, Illinois
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.