A Study of 28431754 (Canagliflozin) on Gastrointestinal Glucose Absorption and Metabolism in Healthy Volunteers

This is a single center study that will be conducted in two Parts (Part 1 and Part 2) to
evaluate the effect of a single-dose of canagliflozin on the absorption of glucose in
healthy volunteers. Part 1 is a pilot (small) study where responses to key pharmocodynamic
(PD) parameters (i.e., specific tests on blood samples to evaluate effects of no treatment
on the body) will be measured to confirm the study design and number of volunteers planned
for Part 2. Part 2 is the main study where volunteers will be randomized (assigned to study
drug or placebo by chance) to receive double-blind (neither the volunteer or study physician
will know the identity of the treatment assigned) treatment with canagliflozin or placebo
(treatment identical in appearance to canagliflozin but contains no active drug) to evaluate
the effect of canagliflozin compared to placebo on gastrointestinal glucose absorption using
a radiolabeled glucose tracer approach (i.e., where a radioactive substance is combined with
glucose allowing the movement of glucose in the body to be traced or detected). A total of
approximately 26 healthy volunteers will be enrolled (up to 6 volunteers in Part 1 and up to
20 volunteers in Part 2). Part 1 and Part 2 of the study will include 2 sequential periods:
Period 1 followed by Period 2 (each Period will last 2 days and will require 1 overnight
stay in the clinical research unit [CRU] with Period 1 and 2 being separated by up to 21
days). Volunteers will participate in Part 1 or Part 2 of the study for a total of
approximately 56 days. Study procedures in Part 1 (Periods 1 and 2) and Part 2 (Periods 1
and 2) will be the same except volunteers in Part 1 will drink 240 ml (8-ounces) of water
and volunteers in Part 2 will be administered study drug 10 minutes prior to the start of
the Mixed Meal Tolerance Test (MMTT), a test that measures the response of blood glucose
levels to a dietary intake. All volunteers (Part 1 and Part 2) will receive an intravenous
(iv) (in the vein) infusion of radiolabeled glucose for 9 hours. About 3 hours after
starting the iv glucose infusion, volunteers will receive a standard meal including 75 g of
a radiolabeled glucose solution. Blood and urine samples will be collected from volunteers
at pre-defined times during the study for PD analysis. Safety will be monitored during the
study by evaluating adverse events and results from clinical laboratory tests, vital signs
measurements, electrocardiograms (ECGs), and physical examinations performed. Volunteers in
Part 1 will receive 240 ml of water 10 minutes before starting of the MMTT in each period
(Periods 1 and 2). Volunteers in Part 2 will receive study drug 10 minutes prior to starting
of the MMTT in treatment sequence 1 (a single 300-mg dose of canagliflozin in Period 1
followed by matching placebo in Period 2) or in treatment Sequence 2 (matching placebo in
Period 1 followed by a single 300-mg dose of canagliflozin in Period 2). Periods 1 and 2
will be separated by 7 to 21 days.