General Information

Trulance (plecanatide) is a guanylate cyclase-C agonist. Plecanatide binds to and activates guanylate cyclase C (GC-C) expressed on epithelial cells lining the GI mucosa, resulting in activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and leading to augmented flow of chloride and water into the lumen of the gut, facilitating bowel movement. 

Trulance is specifically indicated for use in adults for treatment of chronic idiopathic constipation.

Mechanism of Action

Trulance (plecanatide) is a guanylate cyclase-C agonist. Plecanatide binds to and activates guanylate cyclase C (GC-C) expressed on epithelial cells lining the GI mucosa, resulting in activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and leading to augmented flow of chloride and water into the lumen of the gut, facilitating bowel movement. 

Side Effects

The most common adverse reaction associated with the use of Trulance was diarrhea. 

Trulance comes with a Black Box Warning of the risk of serious dehydration in pediatrics: 

• Trulance is contraindicated in patients less than 6 years of age; in young juvenile mice, plecanatide caused death due to dehydration.
• Avoid use of Trulance in patients 6 years to less than 18 years of age. The safety and effectiveness of Trulance have not been established in patients less than 18 years of age.

Dosing/Administration

Trulance is supplied as tablets for oral administration. The recommended dose is 3 mg taken orally once daily, with or without food. For adults with swallowing difficulties, Trulance tablets can be crushed and administered orally either in applesauce or with water or administered with water via a nasogastric or gastric feeding tube. Mixing Trulance crushed tablets in other soft foods or in other liquids has not been tested.

Clinical Trial Results

The FDA approval of Trulance was based on two 12-week, double-blind, placebo-controlled, randomized, multicenter clinical studies in adult patients (study 1 and study 2). In the intention-to-treat (ITT) population, a total of 905 patients (study 1) and 870 patients (study 2) were randomized 1-to-1 to either placebo or Trulance 3 mg, once daily. Over 12 weeks, patients treated with Trulance achieved a significantly greater efficacy responder rate — the primary endpoint defined by the FDA for regulatory approval in CIC — in both studies compared to placebo (study 1: 21 percent versus 10 percent; study 2: 21 percent versus 13 percent, p<0.005 for both studies). Efficacy responders were defined as patients who had at least three complete spontaneous bowel movements (CSBMs) in a given week and an increase of at least one CSBM over baseline in the same week for at least nine weeks out of the 12-week period, including at least three of the last four weeks. In addition, in both studies patients who received Trulance also had improvements as compared to placebo in stool frequency (as measured by the number of spontaneous bowel movements per week), stool consistency (as measured by the Bristol Stool Form Scale) and straining with bowel movements over 12 weeks.