Conduct Phase III CT: CDSCO Panel Tells BDR Pharmaceuticals on Linaclotide Capsules

New Delhi: Granting a waiver of the bioequivalence (BE) study, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the drug maker BDR Pharmaceuticals to conduct a Phase III clinical trial of the new drug Linaclotide Capsules 290 mcg.

This came after BDR Pharmaceuticals International presented the proposal for a grant of permission to manufacture and market the new drug Linaclotide Capsules 290 mg with justification for bioequivalence and a phase III clinical trial waiver.

Linaclotide is a guanylate cyclase-C agonist used to treat different types of constipation, such as irritable bowel syndrome-related constipation, idiopathic constipation, and functional constipation.

Linaclotide is a potent, highly selective agonist of guanylate cyclase-C (GC-C), a soluble and single-membrane-spanning enzyme on the luminal surface of intestinal epithelial cells. GC-C regulates chloride secretion. Linaclotide has a dual mode of action.

Firstly, linaclotide and its active metabolite bind to transmembrane GC-C, which results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevated intracellular cGMP activates the cGMP-dependent protein kinase II (PKG-II), which phosphorylates and activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel expressed on the apical surface of intestinal epithelial cells. CFTR activation promotes the secretion of chloride and bicarbonate ions and inhibits sodium absorption, resulting in increased intestinal fluid and accelerated GI transit.

Secondly, linaclotide exerts anti-nociceptive effects by reducing visceral hypersensitivity. Increased levels of extracellular cGMP in the submucosa inhibit colonic nociceptors, relieving intestinal pain.

At the recent SEC meeting for gastroenterology and hepatology held on June 20, 2024, the expert panel reviewed the proposal for the grant of permission to manufacture and market the new drug Linaclotide Capsules 290 mg with justification for bioequivalence and a phase III clinical trial waiver.

Following a thorough review, the committee found, "Already one of the applicants had been granted permission to conduct a phase III clinical trial with a BE waiver with the proposed new drug Linaclotide Capsules via SEC (Gastroenterology and Hepatology) dated 13.04.2022."

In line with the above, the committee considered only a bioequivalence (BE) study waiver. However, the committee did not recommend the phase III clinical trial waiver and recommended that the firm conduct a phase III clinical trial.

Accordingly, the expert panel suggested that the firm submit a phase III clinical protocol for further consideration.

Also Read: SII high efficacy malaria vaccine launched in Africa