NCT02956044

Interaction of Bexagliflozin With Metformin, Glimepiride and Sitagliptin

A Phase 1, Open-label, Randomized, Three-period, Crossover Study to Evaluate Pharmacokinetic Interaction Between Bexagliflozin Tablets and Metformin, Glimepiride, or Sitagliptin in Healthy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: Theracos · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to examine the drug-drug interaction in your body when given the study drug, bexagliflozin, with three commonly used ant-diabetic medications, metformin, glimepiride or sitagliptin. The study will also evaluate how safe the study drug is and how well the study drug is tolerated when taken with metformin, glimepiride or sitagliptin.

Detailed description

A total of 54 healthy subjects were enrolled and assigned to one of three groups of eighteen. Each group participated in one of three open-label, randomized, three treatment period, crossover studies: * Group 1: Bexagliflozin/metformin drug-drug interaction (DDI) * Group 2: Bexagliflozin/glimepiride DDI * Group 3: Bexagliflozin/sitagliptin DDI For each Group, every subject received a single dose of bexagliflozin tablet, 20 mg, alone, a single dose of an oral hypoglycemic agent (OHA) (1000 mg metformin, 2 mg glimepiride, or 100 mg sitagliptin) alone, and the combination of both (bexagliflozin tablet and OHA) alternately in a crossover fashion, with three treatment periods separated by a washout period of at least 7 days. Within each Group, subjects were randomized to one of six treatment sequences in an equal ratio. To prevent hypoglycemia, subjects assigned to Group 2 (bexagliflozin/glimepiride DDI) received approximately 300 mL of a solution containing 50 g of glucose with study medication at the time of dosing, as well as approximately 75 mL of a solution containing 12.5 g of glucose every 15 minutes for 4 hours post-dose. For each treatment period in Group 1 (bexagliflozin/metformin DDI) and Group 2 (bexagliflozin/glimepiride DDI), subjects were admitted to the clinic on the day before dosing and stayed in the clinic until 48 h post-dose. For Group 3 (bexagliflozin/sitagliptin DDI), subjects stayed in the clinic until 72 h post-dose. For all Groups, blood samples for PK analysis were collected in each period prior to dosing (pre-dose) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose. For Group 3, PK blood samples were also collected at 60 and 72 h post-dose. Plasma concentrations of bexagliflozin and OHAs were determined by validated liquid chromatography tandem mass spectrometry (LC MS/MS) assays. Urine samples for PD analysis were collected in 12 h intervals. For all Groups, urine samples were collected pre-dose (-12 to 0 h) and post-dose at 0 to 12 h, 12 to 24 h, 24 to 36 h, and 36 to 48 h. For Group 3, additional samples at 48 to 60 h and 60 to 72 h post-dose were collected.

Conditions

• Type2 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Bexagliflozin	Bexagliflozin tablets, 20 mg
DRUG	Metformin	1000 mg metformin
DRUG	Glimepiride	4 mg glimepiride
DRUG	Sitagliptin	100 mg sitagliptin

Timeline

• Start date: 2016-11-01
• Primary completion: 2017-03-01
• Completion: 2017-03-01
• First posted: 2016-11-04
• Last updated: 2021-07-22
• Results posted: 2021-07-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study