Acarbose bioequivalence: Exploration of eligible protocol design

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Bioequivalence

Background:

• Acarbose, a poorly absorbed alpha-glucosidase inhibitor, acts locally in the gut.
• Pharmacodynamic (PD) endpoints are preferred over pharmacokinetic (PK) endpoints for evaluating acarbose bioequivalence (BE).
• Optimal protocols for acarbose BE studies using PD endpoints require further investigation.

Purpose of the Study:

• To identify an optimal protocol for establishing acarbose bioequivalence (BE) in healthy Chinese volunteers using pharmacodynamic (PD) endpoints.
• To explore appropriate dosing time/dose and PD parameters for acarbose BE evaluation.

Main Methods:

• Three pilot studies were conducted in healthy Chinese subjects using crossover designs.
• Study 1 assessed dosing time (concomitant vs. 10-min pre-administration of sucrose and acarbose).
• Study 2 identified optimal acarbose dose (1x50mg, 2x50mg, or 3x50mg).
• Study 3 compared test (T) and reference (R) drugs (2x50mg) to determine BE and intra-individual variation.

Main Results:

• Concomitant administration of sucrose and acarbose was found appropriate.
• The optimal dose for acarbose BE studies was determined to be 2x50mg.
• The rectifying method effectively distinguished between formulations, with geometric mean ratios for Cmax, AUC0-2h, and AUC0-4h at 90.06%, 84.55%, and 84.21% respectively.
• Intra-individual variation was approximately 21%, suggesting a required sample size of 55 for the pivotal study.

Conclusions:

• A randomized, balanced, two-way crossover design is suitable for acarbose BE evaluation.
• Concomitant administration of sucrose and acarbose at a 2x50mg dose, utilizing the rectifying method, is recommended.
• The recommended protocol and sample size of 55 provide a basis for future acarbose BE studies.