Prucalopride Tablets for Chronic Idiopathic Constipation Launches, Approved for 180-Day CGT Designation

This article was originally published on Pharmacy Times®. This version has been lightly edited.

The FDA approved a 180-day competitive generic therapy (CGT) designation for prucalopride tablets (Ani Pharmaceuticals), the generic version of the reference listed drug Motegrity (Takeda Pharmaceuticals) that treats adults with chronic idiopathic constipation. The update follows the final FDA approval of its abbreviated new drug application.1,2

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Prucalopride is a selective, high-affinity 5-hydroxytryptamine 4 receptor agonist. Unlike other treatments, prucalopride increases rhythmic movements of the colon muscle to relieve the infrequency of bowel movements in adult patients. Currently, it is unknown if prucalopride is safe to use in children.2

According to a 2016 study published in Digestive Diseases and Sciences3, prucalopride demonstrated both safety and efficacy in both men and women with chronic constipation. The study authors assessed data from 6 large, randomized, double-blind, placebo-controlled phase 3 and 4 clinical trials which evaluated 2 mg once daily prucalopride. For the trials, the primary efficacy end point was the percentage of patients with a mean of 3 or more spontaneous complete bowel movements (SCBMs) per week over the 12 weeks of treatment. Additionally, safety was assessed throughout the 6 trials.3

These trials enrolled a total of 2484 patients, of which most (n = 1887) were women. Patients were randomly assigned to receive either prucalopride (n = 1237) or placebo (n = 1247). A higher proportion of patients who received treatment with prucalopride achieved a mean of 3 or more SCBMs per week (27.8%) compared with those in the placebo group (13.2%; OR 2.68; 95% CI, 2.16-3.33; P < .001). In addition, prucalopride demonstrated a favorable safety and tolerability profile, and both efficacy and safety outcomes were not significantly different between male and female patients.3

In a 2016 systemic review and meta-analysis published in Journal of Neurogastroenterology and Motility4, data from 16 randomized, controlled trials also demonstrated efficacy of prucalopride in patients with chronic constipation. A total of 3943 patients were enrolled and received either 1-, 2-, or 4-mg doses of prucalopride or placebo. Prucalopride was shown to increase the frequency of spontaneous bowel movements (SBMs) per week in all variable doses of 1 mg (SMD, 0.42; 95% CI, 0.18-0.66; P = .006), 2 mg (SMD, 0.34; 95% CI, 0.11-0.56; P = .003]), and 4 mg (SMD, 0.33; 95% CI, 0.22-0.44; P = .00001).4

Potential serious adverse events (AEs) can include depression, unusual changes in mood or behavior, or suicide, with more common AEs being headache, nausea, dizziness, abdominal pain, gas, fatigue, vomiting, diarrhea, abdominal pain, or bloating.2 In the 2016 research, a total of 806 patients (63.3%) in the prucalopride group and 682 patients (53.3%) in the placebo group experienced at least 1 treatment-emergent AE (TEAE), of which most were mild or moderate in severity. No fatal TEAEs occurred. The most common TEAEs (≥ 5%) in the prucalopride group were gastrointestinal disorders (eg, nausea, diarrhea, and abdominal pain) and headache. Few patients reported cardiovascular-related AEs.3 In the review and meta-analysis, observed AEs included headache, abdominal cramps, excessive flatulence, diarrhea, dizziness, and rash, which were more frequent in the prucalopride group.4

References

1. ANI Pharmaceuticals announces the FDA approval and launch of prucalopride tablets with 180-day CGT exclusivity. News release. Ani Pharmaceuticals. January 2, 2025. Accessed January 3, 2025. https://www.globenewswire.com/news-release/2025/01/02/3003434/0/en/ANI-Pharmaceuticals-Announces-the-FDA-Approval-and-Launch-of-Prucalopride-Tablets-with-180-Day-CGT-Exclusivity.html

2. Motegrity® (prucalopride). Accessed January 3, 2025. https://www.motegrity.com/

3. Camilleri M, Piessevaux H, Yiannakou Y, et al. Efficacy and safety of prucalopride in chronic constipation: an integrated analysis of six randomized, controlled clinical trials. Dig Dis Sci. 2016;61(8):2357-2372. doi:10.1007/s10620-016-4147-9

4. Sajid MS, Hebbar M, Baig MK, Li A, Philipose Z. Use of prucalopride for chronic constipation: a systematic review and meta-analysis of published randomized, controlled trials. J Neurogastroenterol Motil. 2016;22(3):412-422. doi:10.5056/jnm16004