Interaction of Bexagliflozin With Metformin, Glimepiride and Sitagliptin

NCT02956044 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: THR-1442-C-453
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• Cmax (Maximum Observed Plasma Concentration)

  Whole venous blood samples of 5 mL were be collected from a peripheral vein in 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 for Group 1 and 2. Pharmacokinetic (PK) blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Cmax was obtained directly from experimental observations.

  Up to 72 hours

• Tmax (Time of Maximum Observed Plasma Concentration)

  Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Tmax was obtained directly from experimental observations.

  Up to 72 hours

• T1/2 (Apparent Terminal Elimination Half-life)

  Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. T1/2 was obtained directly from experimental observations.

  Up to 72 hours

• AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)

  Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. AUC0-inf was estimated for each subject.

  Up to 72 hours

Secondary Outcomes (1)

• Urinary Glucose Excretion up to 0-72 hr

  up to 0-72 hr

Study Arms (9)

Group 1: Bexagliflozin alone

ACTIVE COMPARATOR

Drug: Bexagliflozin

Group 1: Metformin alone

ACTIVE COMPARATOR

Drug: Metformin

Group 1: Bexagliflozin + Metformin

ACTIVE COMPARATOR

Drug: Bexagliflozin; Drug: Metformin

Group 2: Bexagliflozin alone

ACTIVE COMPARATOR

Drug: Bexagliflozin

Group 2: Glimepiride alone

ACTIVE COMPARATOR

Drug: Glimepiride

Group 2: Bexagliflozin + Glimepiride

ACTIVE COMPARATOR

Drug: Bexagliflozin; Drug: Glimepiride

Group 3: Bexagliflozin alone

ACTIVE COMPARATOR

Drug: Bexagliflozin

Group 3: Sitagliptin alone

ACTIVE COMPARATOR

Drug: Sitagliptin

Group 3: Bexagliflozin + Sitagliptin

ACTIVE COMPARATOR

Drug: Bexagliflozin; Drug: Sitagliptin

Interventions

Bexagliflozin DRUG

Bexagliflozin tablets, 20 mg

Group 1: Bexagliflozin + Metformin; Group 1: Bexagliflozin alone; Group 2: Bexagliflozin + Glimepiride; Group 2: Bexagliflozin alone; Group 3: Bexagliflozin + Sitagliptin; Group 3: Bexagliflozin alone

Metformin DRUG

1000 mg metformin

Group 1: Bexagliflozin + Metformin; Group 1: Metformin alone

Glimepiride DRUG

4 mg glimepiride

Group 2: Bexagliflozin + Glimepiride; Group 2: Glimepiride alone

Sitagliptin DRUG

100 mg sitagliptin

Group 3: Bexagliflozin + Sitagliptin; Group 3: Sitagliptin alone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2
• Subjects who are non-smokers for at least 3 months prior to screening
• Subjects who are willing and able to be confined to the clinical research facility as required by the protocol

You may not qualify if:

• Subjects with a clinically significant history of allergy to drugs or latex.
• Subjects with a history of alcohol or drug dependence in the past 12 months.
• Subjects who have donated a significant amount of blood in the past 2 months
• Female subjects who are pregnant or breastfeeding
• Subjects who are not willing to use an adequate form of birth control during the study and for 30 days after discharge from clinic
• Subjects who have taken an investigational drug in the past 30 days or 7 half-lives of the investigational drug, whichever is longer
• 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

Sponsors & Collaborators

• Theracos: lead

Study Sites (1)

Clinical Research Site

Evansville, Indiana, 47710, United States

Location

MeSH Terms

Interventions

bexagliflozin; Metformin; glimepiride; Sitagliptin Phosphate

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Program Director
• Organization: Translational Medicine Group

yhalvorsen@ccib.mgh.harvard.edu

617-726-4236

Study Officials

• Mason Freeman, M.D.

  Massachusetts General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 4, 2016
• Study Start: November 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: July 22, 2021
• Results First Posted: July 22, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)