Study to Evaluate the Effects of a High-Fat Meal on Bexagliflozin in Healthy Subjects

Phase 1

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Bexagliflozin

Registration Number: NCT02820298

Lead Sponsor: Theracos

Brief Summary: The purpose of this study was to investigate the effect of a high-fat meal on the levels of bexagliflozin in the blood in healthy subjects.

Detailed Description: This was a single center, Phase 1, open-label, 2 × 2 crossover study designed to assess the effects of a high-fat meal on the PK of orally administered bexagliflozin tablets in 18 healthy adults. Subjects were randomized 1:1 to receive bexagliflozin tablets with a high-fat meal on day 1 and without a meal on day 8 after an overnight fast or to receive bexagliflozin tablets without a meal on day 1 after an overnight fast and with a high-fat meal on day 8.

Subjects were admitted to the clinic on the day before dosing in each treatment period, and stayed in the clinic until 48 h post-dose.

The subjects dosed in the fed state received an oral bexagliflozin tablet, 20 mg, 30 min after starting to consume a high-fat meal following an overnight fast. The meal was to be ingested in its entirety over an approximate 25-minute period, such that it was completed at least 5 minutes prior to the scheduled time of bexagliflozin dosing for the fed state treatment. Subjects dosed in the fasting state received an oral bexagliflozin tablet, 20 mg, after an overnight fast.

Blood samples for bexagliflozin plasma concentrations were collected at 0 h (pre-dose), and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose. Urine collection in 12 h batches was performed at pre-dose (-12 to 0 h on day 0 and day 7), and at post-dose (0 to 12 h, 12 to 24 h, 24 to 36 h, and 36 to 48 h) intervals.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group 2 - Bexagliflozin in fasted state, then in fed state	Bexagliflozin	Group 2 subjects will take one dose of 20 mg bexagliflozin without food on day 1 after an overnight fast and will take a second dose of bexagliflozin with food on day 8 after an overnight fast.
Group 1 - Bexagliflozin dosed in fed state, then in fasted state	Bexagliflozin	Group 1 subjects will take one dose of 20 mg of bexagliflozin with food on day 1 after an overnight fast and will take a second dose of bexagliflozin without food on day 8 after an overnight fast.

Primary Outcome Measures

Name	Time	Method
AUC0-t (Area Under the Plasma Concentration-time Curve From Time 0 to t)	1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose	Blood samples (2 mL) for bexagliflozin plasma concentrations were collected at 0 h (pre-dose), and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose (days 1-3 in treatment period 1 and days 8-10 in treatment period 2, respectively)
Tmax (Time of Maximum Observed Plasma Concentration)	1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose	Blood samples (2 mL) for bexagliflozin plasma concentrations were collected at 0 h (pre-dose), and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose (days 1-3 in treatment period 1 and days 8-10 in treatment period 2, respectively)
AUC0-∞ (Area Under the Plasma Concentration-time Curve From Time 0 to ∞)	1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose	Blood samples (2 mL) for bexagliflozin plasma concentrations were collected at 0 h (pre-dose), and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose (days 1-3 in treatment period 1 and days 8-10 in treatment period 2, respectively)
Cmax (Maximum Observed Plasma Concentration)	1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose	Blood samples (2 mL) for bexagliflozin plasma concentrations were collected at 0 h (pre-dose), and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose (days 1-3 in treatment period 1 and days 8-10 in treatment period 2, respectively)
T1/2 (Apparent Terminal Elimination Half-life)	1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose	Whole venous blood samples of 3 mL were collected from a peripheral vein prior to dosing and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin; On Day 1 and Day 5 for Study 1, Day 1 and Day 6 for Study 2, Day 1 and Day 4 for Study 3. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).