A0093 - Efficacy and Safety of Prucalopride in Patients With Renal Dysfunction: A Post Hoc Analysis of Phase 3 and 4 Clinical Trials in Chronic Idiopathic Constipation

David C. Kunkel, MD¹, Mena Boules, MD², Brooks D. Cash, MD, FACG³, Anthony Lembo, MD, FACG⁴, Kyle Staller, MD, MPH⁵, William Spalding, MS⁶, Andre' Gabriel, MS, MD⁷, Yunlong Xie, PhD⁷, Yaping Wan, MS⁷, Ashraf Youssef, MD, PhD, MBA⁸, Brian Terreri, PharmD, MBA², Paul Feuerstadt, MD, FACG^9
1University of California San Diego, San Diego, CA; ²Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA; ³University of Texas Health Science Center, Houston, TX; ⁴Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; ⁵Massachusetts General Hospital, Boston, MA; ⁶Takeda Development Center Americas, Inc., Lexington, MA; ⁷Takeda Development Center Americas, Inc., Cambridge, MA; ⁸Takeda Pharmaceuticals U.S.A., Inc., Cambridge, MA; ⁹PACT Gastroenterology Center and Yale University School of Medicine, New Haven, CT

Introduction: Prucalopride is a selective serotonin type 4 receptor agonist indicated to treat chronic idiopathic constipation (CIC) in adults. A post hoc analysis of key phase 3 and 4 clinical trials evaluated the effect of renal function on the efficacy and safety of prucalopride.

Methods: Data from six phase 3 and 4 randomized, double-blind, placebo-controlled trials of prucalopride (2 mg once daily) over 12 weeks were pooled. Patients were stratified by estimated glomerular filtration rate (eGFR; normal renal function, ≥ 90 mL/min/1.73 m²; mild impairment, 60 to < 90 mL/min/1.73 m²; moderate impairment, 30 to < 60 mL/min/1.73 m²). The proportion of patients with a mean frequency of ≥ 3 complete spontaneous bowel movements (CSBMs) per week was analyzed for each eGFR group. Secondary efficacy outcomes included CSBM frequency, stool characteristics, time to first CSBM, rescue medication use, Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire scores, global severity of constipation score and global efficacy of treatment score. Safety data were evaluated descriptively.

Results: Of 2474 patients (mean age: 47.4 years; 75.9% female), 1444 (58.4%) had normal renal function, 869 (35.1%) had mild impairment and 161 (6.5%) had moderate impairment (Table). A greater proportion of patients treated with prucalopride achieved a mean frequency of ≥ 3 CSBMs per week over 12 weeks versus placebo (normal function, 29.8% vs 13.7%, p < 0.001; mild impairment, 26.2% vs 12.8%, p < 0.001; moderate impairment, 17.7% vs 12.2%, p = 0.325; Fig. A). Greater improvements in all secondary efficacy outcomes were observed with prucalopride versus placebo across renal function groups, except for CSBM frequency, rescue medication use, and PAC-SYM and PAC-QOL questionnaire scores in patients with moderate impairment (data not shown). The proportions of patients with any treatment-related treatment-emergent adverse events (TEAEs) were higher with prucalopride than placebo across renal function groups (Fig. B).

Discussion: A greater proportion of patients treated with prucalopride versus placebo achieved a mean frequency of ≥ 3 CSBMs per week among those with normal and mildly impaired renal function. No significant differences were observed between prucalopride and placebo groups among patients with moderately impaired renal function. There was no clear relationship between the incidence of TEAEs and renal function.




Disclosures:


David C. Kunkel, MD¹, Mena Boules, MD², Brooks D. Cash, MD, FACG³, Anthony Lembo, MD, FACG⁴, Kyle Staller, MD, MPH⁵, William Spalding, MS⁶, Andre' Gabriel, MS, MD⁷, Yunlong Xie, PhD⁷, Yaping Wan, MS⁷, Ashraf Youssef, MD, PhD, MBA⁸, Brian Terreri, PharmD, MBA², Paul Feuerstadt, MD, FACG⁹. A0093 - Efficacy and Safety of Prucalopride in Patients With Renal Dysfunction: A Post Hoc Analysis of Phase 3 and 4 Clinical Trials in Chronic Idiopathic Constipation, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.