Objective: This study evaluated the effects of HCTZ
on the pharmacokinetic and pharmacodynamic properties
and tolerability of canagliflozin in healthy
participants.
Methods: This Phase I, single-center, open-label,
fixed-sequence, 2-period study was conducted in healthy
participants. During period 1, participants received
canagliflozin 300 mg once daily for 7 days, followed
by a 14-day washout period. During period 2, participants
received HCTZ 25 mg once daily for 28 days,
followed by canagliflozin 300 mg þ HCTZ 25 mg once
daily for 7 days. Blood samples were taken before and
several times after administration on day 7 of period 1
and on days 28 and 35 of period 2 for canagliflozin and
HCTZ pharmacokinetic analyses using LC-MS/MS.
Blood and urine samples were collected for up to
24 hours after canagliflozin administration on day 1 of
period 1 and day 35 of period 2 for pharmacodynamic
glucose assessment. Tolerability was also evaluated.