Boehringer Ingelheim Told to File Separate Phase IV Trial Plan for Empagliflozin

New Delhi: The Subject Expert Committee (SEC) of the Central Drugs Standard Control Organisation (CDSCO) has directed Boehringer Ingelheim India to submit a separate Phase IV clinical trial protocol for Empagliflozin Tablets 10 mg/25mg within one month, for compliance with the condition of import and marketing permission dated 18/01/2024.

This came after the firm presented the summary of the ongoing Phase III Global Clinical Trial Protocol (EASi-KIDNEY) vide Protocol No. 1378-0006 and requested to consider the data generated from Indian patients with Empagliflozin Tablets 10 mg as the compliance of Phase-IV Clinical Trial condition of import and marketing permission dated 18.01.2024 issued for Empagliflozin Tablets 10 mg and 25 mg for CKD indication.

Further, the firm informed that Empagliflozin Tablets 25 mg are not marketed in the approved indication issued vide permission dated 18.01.2024 and stated that the firm would submit the withdrawal request for the same to CDSCO.

Empagliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), the transporters primarily responsible for the reabsorption of glucose in the kidney. It is used clinically as an adjunct to diet and exercise, often in combination with other drug therapies, for the management of type 2 diabetes mellitus.

The vast majority of glucose filtered through the glomerulus is reabsorbed within the proximal tubule, primarily via SGLT2 (sodium-glucose linked co-transporter-2), which is responsible for ~90% of the total glucose reabsorption within the kidneys. Na+/K+-ATPase on the basolateral membrane of proximal tubular cells utilizes ATP to actively pump Na+ ions into the interstitium surrounding the tubule, establishing a Na+ gradient within the tubular cell. SGLT2 on the apical membrane of these cells then utilizes this gradient to facilitate secondary active co-transport of both Na+ and glucose out of the filtrate, thereby reabsorbing glucose back into the blood—inhibiting this co-transport, then, allows for a marked increase in glucosuria and decrease in blood glucose levels. Empagliflozin is a potent inhibitor of renal SGLT2 transporters located in the proximal tubules of the kidneys and works to lower blood glucose levels via an increase in glucosuria.

After detailed deliberation, Committee recommended submitting the separate Phase IV Clinical Trial Protocol for compliance with the condition of import and marketing permission dated 18.01.2024 within 01 month to CDSCO.