Uji BA/BE FDC Ertugliflozin/Metformin 7,7/850mg Terhadap Produk Inovator pada Subjek Sehat

Summary

This presentation discusses a bioequivalence study of a fixed-dose combination (FDC) tablet containing metformin and ertogliflozin, comparing it to the innovator's metformin product. The study aims to prove bioequivalence based on pharmacokinetic parameters like AUC and CMAX, and evaluates the safety and tolerability of both regimens. Key methods include HPLC-MS/MS for metformin plasma concentration analysis and assessing food effects. The results suggest that the FDC tablet provides similar pharmacokinetics and therapeutic efficacy to the individual drugs, offering a more convenient and effective treatment option for diabetes type 2 patients.

Takeaways

• 😀 The study aims to prove the bioequivalence of a combination tablet of Metformin (850 mg) and Ertogliflozin (7.5 mg) compared to individual components (Metformin and Ertogliflozin).
• 😀 The study evaluates pharmacokinetic parameters like AUC (Area Under the Curve), Cmax (Maximum Concentration), and Tmax (Time to Maximum Concentration) to ensure bioequivalence.
• 😀 The study involves two conditions: fasting and post-meal administration, with 18 participants in the fasting condition and 14 in the post-meal condition.
• 😀 The study uses a randomized, open-label, two-period, two-sequence, single-dose crossover design, ensuring robust data comparison across conditions.
• 😀 Blood samples are collected at multiple time intervals (0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 72 hours) to assess drug concentration in plasma.
• 😀 The bioanalysis is done using HPLC-MS/MS (High-Performance Liquid Chromatography-Tandem Mass Spectrometry) to measure Metformin concentration with high accuracy.
• 😀 The study design follows the regulatory guidelines of BPOM (Indonesian Food and Drug Authority), ensuring compliance with current bioequivalence standards.
• 😀 Participants in the fasting condition receive the study drug after fasting for at least 10 hours, while those in the post-meal condition consume a high-fat meal before the drug administration.
• 😀 Exclusion criteria include individuals with hypersensitivity to Metformin or Ertogliflozin, renal impairment, or those who have recently used certain drugs, ensuring a controlled study population.
• 😀 The study concludes that the FDC tablet of Metformin and Ertogliflozin provides comparable pharmacokinetics to the individual drugs, confirming its bioequivalence and supporting its use as an alternative treatment option for diabetes.

Q & A

What is the main objective of the bioequivalence study discussed in the transcript?

The main objective is to demonstrate the bioequivalence of the metformin combination tablet (FDC) with the innovator metformin product when co-administered with ertogliflosin, based on parameters like AUC and CMAX, and to evaluate the safety and tolerability of both regimens in healthy subjects.

What are the key equipment and materials used in the study?

The study uses HPLC-MS/MS for concentration analysis, pipettes and micropipettes for blood sample collection, centrifuges for plasma separation, clinical monitoring tools such as EKG and blood pressure monitors, and pharmacokinetic analysis software (ENSA version 224).

Why was food intake considered in the study design?

Food intake was evaluated to assess the effect of food on the pharmacokinetics of the metformin-ertogliflosin FDC, comparing the bioavailability of the drug both in a fasting state and after a high-fat meal, to ensure flexibility in drug administration.

What is the significance of using HPLC-MS/MS in the study?

HPLC-MS/MS is used for its high sensitivity and specificity in measuring the concentration of metformin in plasma, ensuring accurate pharmacokinetic data that is essential for validating the bioequivalence between the FDC and individual components.

What were the inclusion criteria for subjects in the study?

Subjects had to be healthy adults aged 18-55 years, with a BMI between 18.5 and 30 kg/m², weighing more than 50 kg, and having normal hematology, blood chemistry, and urinalysis results. They also had to consent to participate in the study.

What were the exclusion criteria for subjects in the study?

Exclusion criteria included individuals with a history of hypersensitivity to SGLT2 inhibitors or metformin, kidney disorders (eGFR < 80 ml/min/1.73 m²), diabetes mellitus, other metabolic disorders, recent use of certain medications, and heavy smokers (more than 10 cigarettes/day).

How was bioequivalence determined in the study?

Bioequivalence was determined by comparing the geometric mean ratios (GMR) of AUC and CMAX for the FDC and individual formulations, with acceptable limits of 80-125%, according to international bioequivalence guidelines.

What is the role of dissolution testing in this study?

Dissolution testing is used to evaluate the release rate of the drug from the tablet formulation. It ensures that more than 85% of the drug is released within 15 minutes, indicating a rapid and optimal dissolution profile for the FDC.

Why was the urinary analysis not performed in this study?

Urinary analysis was not conducted because metformin is not metabolized by the liver and is primarily excreted unchanged via the kidneys. Plasma concentration data was sufficient to represent bioavailability, making urinary analysis unnecessary.

What does the study conclude about the combination of metformin and ertogliflosin in an FDC formulation?

The study concludes that the metformin 850 mg FDC with ertogliflosin has comparable pharmacokinetics to the individual metformin formulation, both in fasting and postprandial conditions. The FDC also shows no significant food effects on its pharmacokinetics and offers improved patient adherence due to fewer tablets.