Alpha lipoic acid bioequivalence study redesigned: a candidate for highly variable drugs

Background and Aims: Alpha lipoic acid 600 mg HR film tablet showed high intra-subject variabilities in bioequivalence studies. In this regard, this study aims to determine whether Alpha lipoic acid 600 mg HR film coated tablet is a highly variable drug. Methods: First, a randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, two-way crossover oral bioequivalence study comparing the test product (Alpha lipoic acid HR film tablet - ILKO Pharmaceuticals, Turkey) with the reference product (Thioctacid®- Meda Pharma, Germany) was conducted in normal, healthy, adult human subjects under fasting conditions (Study 1). Secondly, a randomized, open-label, balanced, two-treatment, four-period, two-sequence, single-dose, fully replicate crossover oral bioequivalence study was conducted in normal, healthy, adult human subjects under fasting conditions (Study 2). Results: Study 1 failed. It had a 90% confidence interval for LnCmax (ng/mL) value between 79.69% – 138.98% with a high intra-subject coefficient of variability (ISCV=57.5%). In study 2 a 90% confidence interval for LnCmax (ng/mL) was found between 88.40% – 129.81% while the ISCV value for LnCmax was 64.5%. Conclusion: The findings suggest that bioequivalence study for Alpha lipoic acid HR film tablet should be redesigned since this is a highly variable drug. Therefore, conventional bioequivalence acceptable limits (80.0%-125.0%) should be adjusted to 69.84% – 143.19% for alpha lipoic acid.