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Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials.
Am J Gastroenterol. 2018 05; 113(5):735-745.AJ

Abstract

OBJECTIVES

Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C).

METHODS

Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or plecanatide (3 or 6 mg) for 12 weeks. The primary efficacy end point was the percentage of overall responders (patients reporting ≥30% reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks). Safety was assessed by adverse events (AEs).

RESULTS

Overall, 2189 individuals were randomized across the two studies and 1879 completed the studies. Demographic and baseline characteristics were similar across treatment groups and between studies. The percentage of overall responders in Study 1 was 30.2% and 29.5% for plecanatide 3 and 6 mg, respectively, vs. 17.8% placebo (P < 0.001 for each dose vs. placebo), and in Study 2 was 21.5% (P = 0.009) and 24.0% (P < 0.001) for plecanatide 3 and 6 mg, respectively, compared to 14.2% for placebo. The percentage of sustained efficacy responders (overall responders plus weekly responders for ≥2 of last 4 weeks of the 12-week treatment period) was significantly greater for both doses of plecanatide vs. placebo across both studies. All secondary end points (stool frequency/consistency, straining, abdominal symptoms) showed statistically significant improvements compared with placebo. The most common AE was diarrhea (3 mg, 4.3%; 6 mg, 4.0%; placebo, 1.0%). Discontinuation due to diarrhea was infrequent (3 mg, 1.2%; 6 mg, 1.4%; placebo, 0).

CONCLUSIONS

Plecanatide significantly improved both abdominal pain and constipation symptoms of IBS-C with minimal associated side effects and high levels of tolerability.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, iL, USA. Clinical Research institute of Michigan, Chesterfield, Mi, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. WR-Clinsearch, Chattanooga, TN, USA. Synergy Pharmaceuticals inc, New York, NY, USA. †Deceased: Paul Eng.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29545635

Citation

Brenner, Darren M., et al. "Efficacy, Safety, and Tolerability of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation: Results of Two Phase 3 Randomized Clinical Trials." The American Journal of Gastroenterology, vol. 113, no. 5, 2018, pp. 735-745.
Brenner DM, Fogel R, Dorn SD, et al. Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials. Am J Gastroenterol. 2018;113(5):735-745.
Brenner, D. M., Fogel, R., Dorn, S. D., Krause, R., Eng, P., Kirshoff, R., Nguyen, A., Crozier, R. A., Magnus, L., & Griffin, P. H. (2018). Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials. The American Journal of Gastroenterology, 113(5), 735-745. https://doi.org/10.1038/s41395-018-0026-7
Brenner DM, et al. Efficacy, Safety, and Tolerability of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation: Results of Two Phase 3 Randomized Clinical Trials. Am J Gastroenterol. 2018;113(5):735-745. PubMed PMID: 29545635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials. AU - Brenner,Darren M, AU - Fogel,Ronald, AU - Dorn,Spencer D, AU - Krause,Richard, AU - Eng,Paul, AU - Kirshoff,Robert, AU - Nguyen,Anhthu, AU - Crozier,Robert A, AU - Magnus,Leslie, AU - Griffin,Patrick H, Y1 - 2018/03/15/ PY - 2017/11/10/received PY - 2018/01/19/accepted PY - 2018/3/17/pubmed PY - 2019/8/7/medline PY - 2018/3/17/entrez SP - 735 EP - 745 JF - The American journal of gastroenterology JO - Am J Gastroenterol VL - 113 IS - 5 N2 - OBJECTIVES: Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C). METHODS: Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or plecanatide (3 or 6 mg) for 12 weeks. The primary efficacy end point was the percentage of overall responders (patients reporting ≥30% reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks). Safety was assessed by adverse events (AEs). RESULTS: Overall, 2189 individuals were randomized across the two studies and 1879 completed the studies. Demographic and baseline characteristics were similar across treatment groups and between studies. The percentage of overall responders in Study 1 was 30.2% and 29.5% for plecanatide 3 and 6 mg, respectively, vs. 17.8% placebo (P < 0.001 for each dose vs. placebo), and in Study 2 was 21.5% (P = 0.009) and 24.0% (P < 0.001) for plecanatide 3 and 6 mg, respectively, compared to 14.2% for placebo. The percentage of sustained efficacy responders (overall responders plus weekly responders for ≥2 of last 4 weeks of the 12-week treatment period) was significantly greater for both doses of plecanatide vs. placebo across both studies. All secondary end points (stool frequency/consistency, straining, abdominal symptoms) showed statistically significant improvements compared with placebo. The most common AE was diarrhea (3 mg, 4.3%; 6 mg, 4.0%; placebo, 1.0%). Discontinuation due to diarrhea was infrequent (3 mg, 1.2%; 6 mg, 1.4%; placebo, 0). CONCLUSIONS: Plecanatide significantly improved both abdominal pain and constipation symptoms of IBS-C with minimal associated side effects and high levels of tolerability. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/29545635/Efficacy_safety_and_tolerability_of_plecanatide_in_patients_with_irritable_bowel_syndrome_with_constipation:_results_of_two_phase_3_randomized_clinical_trials_ L2 - https://Insights.ovid.com/pubmed?pmid=29545635 DB - PRIME DP - Unbound Medicine ER -