The purpose of this study is to examine the drug-drug interaction when given the study drug, bexagliflozin, with one of the most commonly prescribed glucagon-like peptide 1 receptor agonist (GLP-1 RA) exenatide. The study will also evaluate how safe the study drug is and how well the study drug is tolerated when administered with exenatide injection.
This was a phase 1, single center, open-label, 2 × 2 crossover study designed to assess the effects of exenatide injection on the PK and PD of orally administered bexagliflozin tablets. Healthy subjects were randomly assigned to one of two groups with 10 subjects per group. Each group received both the treatments, alternately, in a crossover fashion with the two treatment periods separated by a 7-day washout period. In Treatment Period 1, subjects were admitted to the clinic on day 0, the day before dosing, and stayed in the clinic until 48 h post-dose. After an overnight fast of at least 10 h, subjects in Group 1 received a single oral dose of bexagliflozin tablets, 20 mg, alone 30 min before breakfast, and subjects in Group 2 received a subcutaneous (SC) injection of exenatide at 10 µg twice a day (bid) with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast, followed by the second dose of exenatide alone 1 hr prior to the evening meal. In Treatment Period 2, subjects were admitted to the clinic on day 7, the day before dosing, and stayed in the clinic until 48 hr post-dose. After an overnight fast of at least 10 h, subjects in Group 1 received a SC injection exenatide at 10 µg bid with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast and followed by the second dose of exenatide alone 1 hr prior to the evening meal. Subjects in Group 2 received a single oral dose of bexagliflozin tablets, 20 mg, alone 30 minutes before breakfast. Blood samples for bexagliflozin plasma concentration were collected during each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 hr post-dose. Pre-dose urine samples were collected from -12 to 0 hr for baseline measurement of PD parameters. Post-dose urine samples were collected in four batches: 0 to 12 hr, 12 to 24 hr, 24 to 36 hr, and 36 to 48 hr. Clinical laboratory tests and safety monitoring were conducted during both treatment periods for each group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Bexagliflozin tablets, 20 mg
Byetta® (Exenatide), 10 ug, bid, subcutaneous injection
Clinical Research Site
Evansville, Indiana, United States
Cmax (Maximum Observed Plasma Concentration)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. Cmax was obtained directly from experimental observations.
Time frame: Up to 48 hrs
Tmax (Time of Maximum Observed Plasma Concentration)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. Tmax was obtained directly from experimental observations.
Time frame: Up to 48 hrs
T1/2 (Apparent Terminal Elimination Half-life)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. T1/2 was calculated as the natural log of 2 divided by the terminal phase rate constant.
Time frame: Up to 48 hrs
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. AUC0-inf was calculated using the linear trapezoidal rule, using actual elapsed time values. If the actual time of sample collection was not available, the nominal time was used for the purpose of parameter estimation.
Time frame: Up to 48 hrs
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Urinary Glucose Excretion (UGE)
Post-dose urine was collected without preservative in four batches: 0 to 12 h, 12 to 24 h, 24 to 36 h, and 36 to 48 h collections. After collection, the total volume of each batch and collection time was recorded. UGE, including UGE(t1-t2) and total 0-24 h and 0-48 h UGE were calculated. UGE(t1-t2) was derived from urine volume (Vt1-t2) multiplied by glucose concentration divided by 100.
Time frame: 0-48 hours