At the end of a washout period of 2 weeks, 1464 patients (800 in study A and 664 in study B) were randomly assigned to receive gliclazide MR or the current formulation. The two phase III studies (study A and study B) were comparative trials of gliclazide MR with the currently marketed formulation of gliclazide in different countries. The results of the population PK analysis will be fully published elsewhere. PK and PD data were collected during these phase II/III trials and a population PKPD analysis was performed. The clinical development programme included a phase II parallel dose ranging study, a phase II dose-escalation study and two phase III confirmatory therapeutic equivalence studies. This formulation has modified release characteristics in order to allow a once-daily dosing and to better match release of active principle to the known circadian variations in glycaemia seen in Type 2 diabetes. The clinical development of a modified release formulation of gliclazide (gliclazide MR) provided the opportunity to study the relationship between the pharmacokinetics (PK) of gliclazide and its long-term pharmacodynamic (PD) effect.
This stimulation of insulin secretion leads to a gradual improvement of glycaemic control. Gliclazide improves defective insulin secretion by interacting with specific receptors on pancreatic β-cells. Its effectiveness and safety are well known. Gliclazide is a second-generation sulphonylurea that is used in the treatment of Type 2 diabetes.