Bexagliflozin Drug/Drug Interaction Study With Exenatide Injection

NCT03167411 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: THR-1442-C-458
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Up to 48 hrs

Secondary Outcomes (1)

• Urinary Glucose Excretion (UGE)

  0-48 hours

Study Arms (2)

Bexagliflozin alone

EXPERIMENTAL

Drug: Bexagliflozin

Bexagliflozin with exenatide injection

ACTIVE COMPARATOR

Drug: Bexagliflozin; Drug: Exenatide Injection

Interventions

Bexagliflozin DRUG

Bexagliflozin tablets, 20 mg

Bexagliflozin alone; Bexagliflozin with exenatide injection

Exenatide Injection DRUG

Byetta® (Exenatide), 10 ug, bid, subcutaneous injection

Also known as: Byetta®

Bexagliflozin with exenatide injection

Eligibility Criteria

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

You may qualify if:

• Male and female subjects who were between the ages of 18 and 65 years, inclusive, in good health based on medical history, physical examination, electrocardiogram and routine laboratory tests.
• Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive.
• Subjects who were non-smokers for at least 3 months prior to screening.
• Subjects with adequate venous access at multiple sites in both arms.
• Subjects who were willing and able to be confined to the clinical research facility as required by the protocol.
• Subjects who had the ability to comprehend and who were willing to provide written informed consent in accordance with institutional and regulatory guidelines.

You may not qualify if:

• Subjects who were determined by the investigator or sub-investigator to be unsuitable for participation in the study based on medical conditions or factors that would have influenced adherence to study activities.
• Subjects with a clinically significant history of allergy to drugs or latex.
• Subjects with a history of hypoglycemia.
• Subjects with a history of alcohol or drug dependence in the last 12 months.
• Subjects who donated 400 mL of whole blood within 56 days, 200 mL of whole blood within one month, or donated blood components within 14 days of screening.
• Subjects who used prescription or over-the-counter (OTC) drugs within 14 days prior to the first dose.
• Subjects who used vitamin preparations or supplements (including St. John's Wort and ginseng) within 14 days prior to the first dose .
• Subjects who were not willing to refrain from smoking, alcohol, grapefruit, grapefruit juice or related products, caffeine consumption (including chocolate), and strenuous exercise within 72 h prior to Day 1 and through the end of the PK study.
• Male subjects who did not agree to refrain from donating sperm and use appropriate birth control methods including condoms with spermicide, female partner's use of diaphragm with spermicide, or stable oral, implanted, or injected contraceptive hormones, or with an intrauterine device, or female partner is surgically sterile (i.e. have undergone partial or full hysterectomy, or bilateral oophorectomy) or postmenopausal (absence of menses greater than 12 months and age \>45 years), for a period of 30 days after discharge from the clinic.
• Female subjects of childbearing potential who were not willing to use an adequate method of contraception including bilateral tubal ligation, intrauterine device, diaphragm with spermicide and male partner's use of male condom with spermicide, and to not become pregnant for the duration of the study. Female subjects who were surgically sterile (partial or full hysterectomy, or bilateral oophorectomy) or postmenopausal (absence of menses greater than 12 months and age \>45 years) were eligible if they tested negative on the pregnancy test.
• Subjects who had been treated with an investigational drug within 30 days or 7 half-lives of the investigational drug, whichever is longer, prior to the first dose of study drug in this trial.
• Subjects who had previously received exenatide, or any other GLP-1 RAs within three months from the screening or subjects who had had any GLP-1 RA and suffered an adverse reaction due to the medication.
• Subjects who had previously received bexagliflozin, or any other SGLT2 inhibitors within 3 months from the screening.
• Subjects whose screening ECG demonstrates any one of the following: heart rate \>100 bpm, QRS \>120 msec, QTc \>470 msec (corrected by Fridericia's formula), PR \>220 msec (a subject with PR \>220 msec was generally to be excluded but exceptions may have been allowed at the discretion of the investigator), or any clinically significant arrhythmia.
• Subjects whose sitting blood pressure was above 140/90 mmHg at screening. If the sitting blood pressure at screening was above 140/90 mmHg, one repeat measurement was allowed and the subject may have been randomized if the blood pressure was 140/90 +/-5 mm Hg at the discretion of the Investigator.

Sponsors & Collaborators

• Theracos: lead

Study Sites (1)

Clinical Research Site

Evansville, Indiana, 47710, United States

Location

MeSH Terms

Interventions

bexagliflozin; Exenatide

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Albert Collinson
• Organization: Theracos Sub, LLC

acollinson@theracos.com

(508) 630-2129

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: May 24, 2017
• First Posted: May 30, 2017
• Study Start: May 24, 2017
• Primary Completion: June 29, 2017
• Study Completion: June 29, 2017
• Last Updated: May 28, 2021
• Results First Posted: May 28, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)