Clinical Trial on Glimepiride 2mg Single Oral Dose in Healthy Volunteers: Need for Preventive Management of Hypoglycaemia

Abstract

Objective: The objective of our study was to assess the bioequivalence of 2 different glimepiride formulations at a dose of 2 mg. We also describe the adverse events detected, with special emphasis on those directly related to administration of glimepiride, as well as the preventive action taken. Research Design and Methods: We performed a randomized, open-label, crossover, 2-period bioequivalence study in which a single oral dose of each formulation was administered immediately after reakfast to 30 healthy volunteers, with a 7-day washout period between doses. Extra oral carbohydrates and intravenous glucose-saline solution were administered according to blood sugar level to prevent symptomatic hypoglycaemia. An analysis of variance was performed for the different Ln-transformed pharmacokinetic parameters. Results: Twenty-nine subjects were evaluated. A total of 28 AEs were detected, and 9 of them had a possible or close relationship. Of these, five were symptomatic hypoglycaemia (glucose blood level of 40-60 mg/dl). The symptoms were of mild to moderate intensity, since all subjects had received an adequate supply of carbohydrates and extra glucose infusion before the events occurred. All cases resolved completely after adjustment of the glucose infusion. The remaining 19 adverse events were recorded as doubtful or not related to the drug. Conclusions: Optimization of the intravenous glucose administration schedule can prevent severe symptomatic hypoglycaemia, which could jeopardize the health status of subjects involved in a ioequivalence study with glimepiride. Our findings justify the use of such control measures and their applicability in other studies with hypoglycaemic drugs.