Submit BE Raw Data, Interaction Study on Dapagliflozin-Rosuvastatin FDC: Expert Panel Tells Pure and Cure
New Delhi: In line with the proposal presented by Pure and Cure Healthcare for the Dapagliflozin plus Rosuvastatin film-coated tablet, the Subject Expert Committee (SEC), functional under the Central Drugs Standard Control Organization (CDSCO), has opined that the raw data of the bioequivalence (BE) study report for the pharmacokinetics of each subject should be submitted.
In addition, the expert panel suggested that the firm should submit a drug-drug interactions study, as individual drugs have different drug profiles in respect of their mechanisms.
This came as the drug maker Pure and Cure Healthcare presented the proposal along with the bioequivalence (BE) study report and revised Phase III clinical trial protocol before the committee.
Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and it was the first SGLT2 inhibitor to be approved for managing diabetes mellitus type 2. When combined with diet and exercise in adults, dapagliflozin helps to improve glycemic control by inhibiting glucose reabsorption in the proximal tubule of the nephron and causing glycosuria.
Dapagliflozin inhibits the sodium-glucose cotransporter 2 (SGLT2), which is primarily located in the proximal tubule of the nephron. SGLT2 facilitates 90% of glucose reabsorption in the kidneys and so its inhibition allows for glucose to be excreted in the urine. This excretion allows for better glycemic control and potentially weight loss in patients with type 2 diabetes mellitus.
Rosuvastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Rosuvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low-density lipoprotein (LDL) receptors, which increases hepatic uptake of LDL. Rosuvastatin also inhibits hepatic synthesis of very low-density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL.
At the recent SEC meeting for endocrinology and metabolism, the expert panel reviewed the proposal along with the bioequivalence (BE) study report and revised Phase III clinical trial protocol for Dapagliflozin Propanediol Monohydrate eq. to Dapagliflozin 10 mg/10 mg plus Rosuvastatin Calcium IP eq. to Rosuvastatin 10 mg/20 mg film-coated tablet.
After detailed deliberation, the committee opined that:
1. Raw data of the BE study report for the pharmacokinetics of each subject should be submitted.
2. The firm should submit a drug-drug interactions study, as individual drugs have different drug profiles in respect of their mechanisms.
