Ironwood Pharmaceuticals and Allergan have started a Phase IIb trial, which will evaluate linaclotide colonic release in adults suffering from irritable bowel syndrome with constipation (IBS-C).
Linaclotide is a guanylate cyclase-C (GC-C) agonist. After binding to a GC-C receptor, it is thought to decrease pain-sensing nerve activity and increase fluid secretion in the intestine.
Two forms of linaclotide are being evaluated in the trial, which aims to support advancement of two distinct products into late development stages.
These products are intended for patients with IBS-C, or other gastrointestinal (GI) disorders with lower abdominal pain as a predominant symptom.
The company intends to report data from the Phase IIb trial in the second half of 2016.
The FDA has already approved daily 145mcg linaclotide capsules for adults with chronic idiopathic constipation (CIC) and daily 290mcg capsules for adults with IBS-C.
An expected total of 520 adults with IBS-C will be enrolled in the double-blind, placebo-controlled, multi-site Phase IIb trial, and randomised into one of eight groups.
One group will receive a placebo, one will receive 290mcg linaclotide, three groups will receive various doses of colonic release formulation 1 (CR1) at 30mcg, 100mcg or 300mcg, and three groups will receive various doses of colonic release formulation 2 (CR2) at 30mcg, 100mcg or 300mcg.
The company noted the inclusion of the approved 290mcg formulation as a positive control for the trial, in which all doses will be administered orally, once a day, for 12 weeks.
The trial will evaluate the safety and efficacy of each linaclotide dose and formulation, including its effect on abdominal pain relief and complete spontaneous bowel movement (CSBM) frequency.
It will also assess other abdominal and bowel symptoms commonly experienced by IBS-C patients.
Allergan brand research and development executive vice-president David Nicholson said: "Abdominal pain is a key symptom of many gastrointestinal diseases, including IBS-C. Millions of patients are impacted by abdominal pain, and they have few prescription options.
"Our goal in this trial is to evaluate the potential of our two linaclotide colonic release formulations to provide enhanced abdominal pain relief to patients suffering from IBS-C, as well as to evaluate the differences between the two formulations, and inform a path forward for developing a drug that can reduce gastrointestinal pain in other disorders, such as other types of IBS, ulcerative colitis and diverticulitis."
The trial also aims to assess how the two colonic release formulations compare to each other, and to the approved 290mcg formulation of linaclotide, with the goal of identifying appropriate doses and formulations for Phase III trials.