Setback to Torrent: CDSCO Panel Rejects Phase III Waiver Plea for Prucalopride Over Safety Data Gaps
New Delhi: Citing that Torrent Pharmaceuticals has not presented adequate safety data on the synergistic effect of added excipients (propylene glycol, Glycerol and sorbitol) with prucalopride in the applied formulation, the Subject Expert Committee (SEC) functioning under the Central Drugs Standard Control Organization (CDSCO) has rejected the proposal for the manufacture and marketing of prucalopride oral solution 0.2 mg/ml for the treatment of idiopathic constipation in adults with a waiver of the Phase III clinical trial.
This came after Torrent Pharmaceuticals presented a proposal for a grant of permission to manufacture and market Prucalopride oral solution 0.2 mg/ml for the treatment of idiopathic constipation in adults with a waiver of the Phase III clinical trial.
In addition, the firm presented a bioequivalence study report along with justification for the synergistic effect of added excipients on CNS in applied formulation.
Prucalopride is a dihydrobenzofurancarboxamide derivative from the benzofurane family that selectively stimulates 5-HT4 receptors and thus, it presents enterokinetic properties.
Prucalopride acts as a selective stimulator of the 5-HT4 receptors while having no interaction with the hERG channel or 5-HT1 receptors, which reduces significantly the cardiovascular risk found in other similar drugs. 5-HT4 receptors can be found throughout the gastrointestinal tract, primarily in smooth muscle cells, enterochromaffin cells, and the myenteric plexus. Its activation produces the release of acetylcholine, which is the major excitatory neurotransmitter in the GI tract.
Hence, prucalopride stimulates motility by interacting specifically with 5-HT4 receptors in the GI tract, which causes a release of acetylcholine and further contraction of the muscle layer of the colon and relaxation of the circular muscle layer, leading to the propulsion of luminal content.
At the recent SEC meeting for gastroenterology and hepatology held on 29th July, 2025, the expert panel reviewed the proposal for a grant of permission to manufacture and market Prucalopride oral solution 0.2 mg/ml for the treatment of idiopathic constipation in adults with a waiver of the Phase III clinical trial.
After detailed deliberation, the committee opined that the firm has not presented adequate safety data on the synergistic effect of added excipients (propylene glycol, Glycerol and sorbitol) with prucalopride in the applied formulation.
Accordingly, the committee did not recommend a waiver of the phase III clinical trial.
