Linaclotide works well for functional constipation in children

The guanylate cyclase C agonist linaclotide helps increase the frequency of bowel movements in children with functional constipation, according to data from a phase III trial.

A total of 328 patients (55 percent girls) between 6 and 17 years of age who met the modified Rome III criteria for functional constipation were included in the trial. These patients were randomly assigned to receive treatment with either oral linaclotide 72 μg (n=164) or placebo (n=164) once daily for 12 weeks.

The primary efficacy endpoint was change from baseline in the 12-week frequency rate of spontaneous bowel movements (SBMs; occurring in the absence of rescue medication on the calendar day of or before the bowel movement) per week. Any changes in stool consistency over the 12-week treatment period were also evaluated as the secondary efficacy endpoint. Efficacy and safety were analysed in the modified intention-to-treat population and safety population, respectively.

Of the patients, 293 (89 percent) completed the trial. Over the 12-week treatment period, the mean frequency rate of SBMs increased from 1.16 at baseline to 3.41 per week with linaclotide and from 1.28 to 2.29 per week with placebo. Compared with placebo, linaclotide led to a significant increase in SBM frequency (least-squares mean [LSM], 2.22 vs 1.05 SBMs per week; p<0.0001).

Additionally, linaclotide was associated with a significant improvement in stool consistency compared with placebo (LSM, 1.11 vs 0.69; p=0.0001).

In terms of safety, diarrhoea was the most frequent treatment-emergent adverse event (TEAE) in the linaclotide group (4 percent vs 2 percent), while COVID-19 was the most common TEAE in the placebo group (3 percent vs 2 percent). The most frequent TEAE related to treatment was diarrhoea (4 percent with linaclotide vs 1 percent with placebo).

A serious adverse event of special interest, which was a treatment-related severe diarrhoea resulting in dehydration and hospitalization, occurred in one patient in the linaclotide group. This event resolved without sequelae following administration of intravenous fluids. None of the patients died during the study.