Interaction of Bexagliflozin With Metformin, Glimepiride and Sitagliptin

NCT ID: NCT02956044

Last Updated: 2021-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2017-03-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1: Bexagliflozin alone

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

Bexagliflozin tablets, 20 mg

Group 1: Metformin alone

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

1000 mg metformin

Group 1: Bexagliflozin + Metformin

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

Bexagliflozin tablets, 20 mg

Metformin

Intervention Type: DRUG

1000 mg metformin

Group 2: Bexagliflozin alone

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

Bexagliflozin tablets, 20 mg

Group 2: Glimepiride alone

Group Type: ACTIVE_COMPARATOR

Glimepiride

Intervention Type: DRUG

4 mg glimepiride

Group 2: Bexagliflozin + Glimepiride

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

Bexagliflozin tablets, 20 mg

Glimepiride

Intervention Type: DRUG

4 mg glimepiride

Group 3: Bexagliflozin alone

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

Bexagliflozin tablets, 20 mg

Group 3: Sitagliptin alone

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

100 mg sitagliptin

Group 3: Bexagliflozin + Sitagliptin

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

Bexagliflozin tablets, 20 mg

Sitagliptin

Intervention Type: DRUG

100 mg sitagliptin

Interventions

Bexagliflozin

Bexagliflozin tablets, 20 mg

Intervention Type: DRUG

Metformin

1000 mg metformin

Intervention Type: DRUG

Glimepiride

4 mg glimepiride

Intervention Type: DRUG

Sitagliptin

100 mg sitagliptin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2

2. Subjects who are non-smokers for at least 3 months prior to screening

3. Subjects who are willing and able to be confined to the clinical research facility as required by the protocol

Exclusion Criteria

1. Subjects with a clinically significant history of allergy to drugs or latex.

2. Subjects with a history of alcohol or drug dependence in the past 12 months.

3. Subjects who have donated a significant amount of blood in the past 2 months

4. Female subjects who are pregnant or breastfeeding

5. Subjects who are not willing to use an adequate form of birth control during the study and for 30 days after discharge from clinic

6. Subjects who have taken an investigational drug in the past 30 days or 7 half-lives of the investigational drug, whichever is longer

7. Subjects who had previously received anti-diabetic medication, including metformin, sitagliptin, glimepiride or drugs of the same class (i.e. biguanides, DPP-4 inhibitors or sulfonylureas), or SGLT2 inhibitors, in the past 3 months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Theracos

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mason Freeman, M.D.

Role: STUDY_CHAIR

Massachusetts General Hospital

Locations

Clinical Research Site

Evansville, Indiana, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

THR-1442-C-453

Identifier Type: -

Identifier Source: org_study_id