Lower Linaclotide Dose Effective, Safe in Chronic Idiopathic Constipation

By Anne Harding

NEW YORK (Reuters Health) - Linaclotide at a daily dose of 72 mcg is an effective treatment for adults with chronic idiopathic constipation (CIC), with a lower risk of diarrhea than the standard higher dose, according to a new phase 3 trial.

“The 72 mcg dose of LINZESS provides physicians with dosing flexibility so they can tailor treatment of their patients with CIC based on individual clinical presentation and tolerability,” Dr. Michael L. Hall of Ironwood Pharmaceuticals in Cambridge, Massachusetts, the company that makes the drug, told Reuters Health by email. The findings were published online August 22 in the American Journal of Gastroenterology.

As many as 35 million U.S. adults suffer from CIC, Dr. Hall noted. Linaclotide, a guanylate cyclase-C agonist, has been approved in the U.S., Mexico and Canada at 145 mcg for treating CIC, and was recently approved at the 72-mcg dose by the U.S. Food and Drug Administration.

To evaluate the safety and efficacy of the lower dose, the researchers enrolled 1,223 patients with CIC to receive 72 mcg, 145 mcg, or placebo for 12 weeks. The study’s primary endpoint was a complete spontaneous bowel movement (CSBM) response, defined as at least three CSBMs per week and an increase of at least one CSBM from baseline during the same week for at least nine weeks.

CSBM occurred in 13.4% of patients on 72 mcg of linaclotide, in 12.4% of those on 145 mcg and in 4.7% of those on placebo (p<0.0001).

Article continues on page 2

Sustained response, defined as meeting weekly criteria for CSBM for three of the four final weeks of the study, occurred in 12.4% of patients on 72 mcg of linaclotide, in 11.2% with 145 mcg and in 4.2% with placebo.

Diarrhea was the most common adverse event, and was mild for most patients. None of the placebo group patients withdrew from the study due to diarrhea, versus 2.4% of patients on 72 mcg and 3.2% of patients on 145 mcg.

Secondary endpoints included bowel and abdominal symptoms, nine in 10 of which improved in the patients on 72 mcg linaclotide versus placebo.

“LINZESS was studied for up to 26 weeks and shown to be effective when taken once daily. It should be taken once daily as prescribed by a physician to help patients proactively manage their symptoms,” Dr. Hall said.

“The 72 mcg dose provides another dosing option for physicians treating this very large and diverse patient population,” he added. “The unmet need is huge, and we believe the 72 mcg dose is playing an important role in helping these patients.”

The study was funded by Ironwood Pharmaceuticals, Inc, and Forest Research Institute, an affiliate of Allergan, PLC.

SOURCE: https://bit.ly/2vPYDb3

Am J Gastroenterol 2017.

(c) Copyright Thomson Reuters 2017. Click For Restrictions - https://about.reuters.com/fulllegal.asp