FDA Approves Prucalopride for Chronic Idiopathic Constipation

The US Food and Drug Administration (FDA) has approved Shire’s prucalopride (Motegrity) for the treatment of chronic idiopathic constipation (CIC). Prucalopride is a selective serotonin-4 (5-HT 4 ) receptor agonist that is administered as a once-daily, oral treatment. By enhancing colonic peristalsis to increase bowel motility, it offers a different class of treatment for CIC.

Six double-blind, placebo-controlled, randomized, multicenter clinical studies lasting 12 weeks (studies 1-5) or 24 weeks (study 6) evaluated the efficacy of once-daily treatment with prucalopride. Most of the 2,484 patients were female (76%) and Caucasian (76%) and had an average age of 47 (+/- 16 years).

Across 5 of 6 trials, the primary endpoint was achieved significantly by more patients administered prucalopride (an average of ≥3 complete spontaneous bowel movements [CSBMs] per week over 12 weeks, considered normalization of BM frequency) compared to those in the placebo group (19%-38% prucalopride ≥2 mg vs. 10%-20% placebo).

As early as week 1, rapid responses were observed in the patients administered prucalopride, and improvements maintained throughout 12 weeks of treatment.

The FDA has requested that 5 post-marketing studies be conducted in order to assess the pharmacokinetics, efficacy, and safety of prucalopride in pediatric patients with CIC (6 months old to less than 18 years of age) and pregnant and lactating women with CIC treated with prucalopride.

Dyspnea, rash, pruritus, urticaria, and facial edema are treatment reactions that have been observed. Prucalopride is contraindicated in patients with a history of hypersensitivity to prucalopride and “in patients with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn’s disease, ulcerative colitis, and toxic megacolon/megarectum.”

Headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue include the most common adverse reactions (≥2%). While discontinuation of prucalopride due to adverse events was low (5% prucalopride 2 mg once daily; 3% placebo), reported adverse events included diarrhea or headache, which typically resolved within a few days.