Constipation treatment successful in late-stage trials

Symptoms of chronic constipation improve significantly following treatment with a new orally administered peptide, two Phase III trials have shown.

Complications of chronic constipation include haemorrhoids, faecal impaction (shown here on CT scan) and intestinal perforation | Photo: SPL
Complications of chronic constipation include haemorrhoids, faecal impaction (shown here on CT scan) and intestinal perforation | Photo: SPL

Linaclotide is a peptide agonist of guanylate cyclase type C, which is expressed on the epithelial cells that line the intestine. Activation of this receptor modulates abdominal pain sensation and secretion of fluid and electrolytes into the intestine.

The two trials, reported at this year's , enrolled a total of 1,276 patients. Investigators randomised participants to receive 133 micrograms or 266 micrograms of linaclotide daily, or placebo, for 12 weeks. The study population was 89% female, with an average age of 48 years.

In both trials, the primary end point was achievement of three or more complete spontaneous bowel movements (CSBM) per week, with an increase from baseline of at least one CSBM per week for a minimum of nine weeks.

The results of the showed that patients receiving linaclotide were more than twice as likely to respond to linaclotide as to placebo. The proportion of patients who achieved the primary end point was 16% in the group given 133 micrograms of linaclotide daily and 21.3% in the group on the 266 microgram dose, compared with 6% in the placebo group (p=0.0012 and p<0.0001, respectively, versus placebo).

In the , the difference was even greater - 21.2% and 19.4% of patients receiving the lower and higher doses of linaclotide achieved the primary end point, respectively, compared with only 3.3% of those given placebo (p<0.0001 for both doses versus placebo).

Diarrhoea, flatulence and abdominal pain were the most commonly reported adverse events. At each dose of linaclotide, approximately 4% of patients discontinued treatment as a result of diarrhoea; the corresponding percentage in the placebo group was 0.5%.

Linaclotide, which is being developed in Europe by , is also undergoing Phase III testing for irritable bowel syndrome with constipation. Results from these trials are expected in the second
half of 2010.

 

Want news like this straight to your inbox?
Sign up for our bulletins

Have you registered with us yet?

Register now to enjoy more articles and free email bulletins

Already registered?
Sign in

More from intelog

Asthma and COPD Preparations and Compatible Devices

Asthma and COPD Preparations and Compatible Devices

Available presentations of bronchodilators and anti-inflammatories.

Ranitidine in short supply after contamination fears prompt precautionary recall

Ranitidine in short supply after contamination fears prompt precautionary recall

GPs have reported shortages of ranitidine following...

Drug shortages - live tracker

Drug shortages - live tracker

Added: Alzhok and ranitidine oral soln.
Use our...

Excessive steroid dosing highlighted in inflammatory bowel disease

Excessive steroid dosing highlighted in inflammatory bowel disease

Some patients with Crohn's disease or ulcerative colitis...