Evaluation of Food Effect on the Pharmacokinetics of Sustained Release Metformin in Healthy Indian Volunteers
Status:
Completed
Trial end date:
2012-02-21
Target enrollment:
Participant gender:
Summary
Metformin hydrochloride in its immediate release (IR) form has been successfully used for
decades in the treatment of type 2 diabetes; however the IR formulation may be associated
with gastrointestinal side effects (especially nausea, diarrhea) in 20-30% patients, which
can limit the tolerated dose, reduce adherence and result in discontinuation of therapy.
Metformin hydrochloride extended release formulations have been developed to overcome these
problems. In India, extended release formulations of metformin hydrochloride include
metformin SR 1000mg tablet and combination of metformin hydrochloride SR 1000mg/glimepiride
2mg tablet. In the combination tablet, only metformin hydrochloride is in the extended
release form. In view of the fact that extended release metformin hydrochloride is usually
recommended with a meal, that food is known to affect the pharmacokinetic (PK) parameters of
metformin and that there is a potential for dose dumping with extended release formulations
that may lead to side effects similar to IR formulations, a study to estimate the magnitude
of the food effect for these formulations in fed state compared to the fasting state is
warranted. This study will be a randomized, single-center, open-label, single-dose,
three-period, 6 sequence crossover study in 30 healthy adult volunteers to estimate the
bioavailability of metformin from metformin hydrochloride 1000mg SR tablet given in fasting
condition relative to metformin hydrochloride 1000mg SR tablet and a fixed dose combination
of metformin hydrochloride 1000mg SR /glimepiride 2mg tablet, each given in fed condition.
The safety and tolerability profile of metformin SR 1000mg tablet and metformin hydrochloride
SR 1000mg/glimepiride 2mg tablet will also be evaluated in this study. The primary PK
endpoints will be Cmax and AUC (0-∞). The secondary PK endpoints will include AUC (0-t), Tmax
, T lag, Kel and t1/2. Safety endpoints will include vital signs, ECG, physical examination,
clinical laboratory tests and adverse event reporting.