Clinical–alimentary tractEffect of 5 Days Linaclotide on Transit and Bowel Function in Females With Constipation-Predominant Irritable Bowel Syndrome
Section snippets
Study Design, Participants, and Medication
This study was a single-site, double-blind, placebo-controlled, randomized, multiple repeat-dose study evaluating the pharmacodynamic effects of linaclotide, 100 and 1000 μg, and placebo administered orally once daily for 5 days in patients with IBS-C. We enrolled 36 female, nonpregnant, nonbreastfeeding participants aged 18–65 years with IBS-C, based on Rome II criteria.14 The study was approved by the Mayo Clinic Institutional Review Board, and all participants signed informed consent.
Participants, Study Conduct, and Completion
Forty-seven patients were recruited for the study, as shown in Figure 2. Six were ineligible because of concomitant medication or evidence of rectal evacuation disorder. Five were not randomized to treatment because their colonic transit at baseline was too fast, relative to the preset criteria. Demographic and baseline colonic transit data of all randomized patients are shown in Table 1. The linaclotide and placebo groups were similar regarding baseline values of colonic transit. All 36
Discussion
This study demonstrates that the novel, first-in-class GC-C agonist linaclotide accelerates ascending colon emptying and dose dependently improves bowel functions in female patients with IBS-C. There was also acceleration of overall colonic transit at 48 hours, but this was not significant at 24 hours. These results are consistent with prior findings of the pharmacodynamic effects of linaclotide in animals and observed changes in bowel function noted in both healthy volunteers during phase I
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Description of trial analysis and access to data: This is a phase IIa trial. The statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically, serious adverse events as defined in federal guidelines) have been independently confirmed by a biostatistician (Dr. Zinsmeister) who is not employed by Microbia. The corresponding author, Dr. Camilleri, had full access to all of the data and takes full responsibility for the veracity of the data and analysis.
Supported by Microbia, Inc. and grants RO1-DK54681 and K24-DK02638 from the National Institutes of Health (to M.C.) for research on irritable bowel syndrome.
The authors thank Cindy Stanislav for excellent secretarial support.
Employment and Disclosures: The authors, Drs. Kurtz, Sharma, Johnston, and Currie, are employees of Microbia. Dr. Kurtz facilitated planning and operational aspects as well as direct scientific guidance to this study. Dr. Sharma contributed to the scientific aspects and data management of the study. Dr. Johnston provided medical input to the design and interpretation of the data analysis from the study. Dr. Currie is the inventor of linaclotide and provided scientific direction to the development of the clinical studies.