Study design and rationale of a dose-ranging trial of LX4211, a dual inhibitor of
SGLT1 and SGLT2, in type 2 diabetes inadequately controlled on metformin
monotherapy.
Author(s): Lapuerta P(1), Rosenstock J, Zambrowicz B, Powell DR, Ogbaa I, Freiman J, Cefalu
WT, Banks P, Frazier K, Kelly M, Sands A.
Affiliation(s): Author information:
(1)Department of Clinical Development, Lexicon Pharmaceuticals, Inc., 350 Carter
Road, Princeton, NJ 08540, USA. plapuerta@lxrx.com
Publication date & source: 2013, Clin Cardiol. , 36(7):367-71
Sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) are the major cellular
transporters responsible for gastrointestinal (GI) glucose absorption and renal
glucose reabsorption, respectively. LX4211, a dual inhibitor of SGLT1 and SGLT2,
reduces glucose absorption from the GI tract and enhances urinary glucose
excretion. Although several SGLT2-selective inhibitors have been tested in large
phase 2 studies, dual inhibition of SGLT1 and SGLT2 is novel at this stage of
drug development, and it has implications for clinical-trial design. In this
article, we describe the design and rationale of a phase 2, multicenter,
randomized, double-blind, placebo-controlled, parallel group study to evaluate
the safety and efficacy of LX4211 in subjects with type 2 diabetes mellitus who
have inadequate glycemic control on metformin monotherapy. The primary endpoint
is the change in glycated hemoglobin A1c from baseline to week 12. Secondary
endpoints include the proportion of subjects achieving a glycated hemoglobin A1c
value of <7%, change from baseline in fasting plasma glucose and postprandial
glucose (as part of an oral glucose tolerance test), body weight, and blood
pressure. Safety is evaluated with particular focus on hypoglycemia, GI symptoms,
and incidence of genitourinary tract infections.
|