Johnston, J.M., Kurtz, C.B., Drossman, D.A., Lembo, A.J., Jeglinski, B.I., MacDougall, J.E., . . . Currie, M.G. (2009). Pilot study on the effect of linaclotide in patients with chronic constipation. American Journal of Gastroenterology, 104, 125–132.

To evaluate the safety, tolerability, and efficacy of linaclotide in patients with chronic constipation.

Patients recorded data related to daily bowel habits and called into a voice response system daily to record their medications taken and bowel movements. Patients were randomized to receive 100, 300, or 1,000 mcg of linaclotide or placebo once daily in the morning, in the fasting state.

• The study reported on a sample of 36 patients.
• Mean patient age was 45.2 years (SD = 12.17).
• The sample comprised 88% women and 12% men.
• Diagnosis-specific information was not provided.
• Patients were excluded if they had pelvic floor dysfunction.
• All patients had experienced constipation for 12 or more weeks within the past year.

• Multi-site
• Outpatient
• United States

This was a randomized, double-blind, placebo-controlled, parallel group, phase IIA study.

• Bristol Stool Form Scale
• Ease of Passage Scale
• Subjective patient-reported outcomes of discomfort and overall relief on seven-point Likert-type scales
• National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0

• All doses of linaclotide produced a three-fold greater increase in number of spontaneous bowel movements compared to placebo (p = 0.047).
• Weekly stool frequency increased in a dose-related manner.
• Stool consistency improved in all dose groups in a dose-related manner compared to placebo (p < 0.01).
• Patient-reported outcomes improved with all doses of linaclotide, but were not statistically different than those seen with placebo.
• No severe adverse events were reported. The most common adverse event was diarrhea.

Linaclotide appeared to improve symptoms of chronic constipation and was well-tolerated overall.

• The sample size was small (fewer than 100).
• The study was likely underpowered.

The usefulness of linaclotide for patients with cancer who have constipation is not yet known. This medication is a peptide that binds to specific receptors on the membrane of intestinal enterocytes and may increase efflux into the intestinal lumen with concomitant fluid secretion. Those effects may improve stool consistency and transit time. Nurses should be aware that a variety of new medications aimed at management of constipation with various mechanisms of action are being developed. Applicability to patients with cancer has not yet been studied.