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Trial · Interventional

CompletedPhase 1Results postedRegistry data

Bexagliflozin Drug/Drug Interaction Study With Exenatide Injection

Overview

Status
Completed
Phase
Phase 1
Enrollment
20 participants (actual)
Sponsor
Theracos · Industry
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
24 May 2017
Primary completion
29 Jun 2017
Completion
29 Jun 2017
First posted
30 May 2017
Last update posted
28 May 2021
Conditions
Type2 Diabetes Mellitus

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20172018
  1. Ph 1

    Bexagliflozin Drug/Drug Interaction Study With Exenatide Injection

    NCT03167411

    24 May 2017 to 29 Jun 2017

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • BexagliflozinDrug
  • Exenatide InjectionDrug

Arms2

  • Experimental

    Bexagliflozin alone

  • Active comparator

    Bexagliflozin with exenatide injection

Primary outcomes4

Outcomes the sponsor listed as primary.

  1. Cmax (Maximum Observed Plasma Concentration)

    Time frame · Up to 48 hrs

    Registry description

    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.

  2. Tmax (Time of Maximum Observed Plasma Concentration)

    Time frame · Up to 48 hrs

    Registry description

    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.

  3. T1/2 (Apparent Terminal Elimination Half-life)

    Time frame · Up to 48 hrs

    Registry description

    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.

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

    Time frame · Up to 48 hrs

    Registry description

    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.

Secondary outcomes(1)
  1. Urinary Glucose Excretion (UGE)

    Time frame · 0-48 hours

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeGeometric mean· Up to 48 hrs

Cmax (Maximum Observed Plasma Concentration)

GroupValue (ng/mL)Spread
Bexagliflozin95.933.6
Bexagliflozin With Exenatide121.633.1
Primary outcomeMedian· Up to 48 hrs

Tmax (Time of Maximum Observed Plasma Concentration)

GroupValue (hours)
Bexagliflozin2.00
Bexagliflozin With Exenatide5.00
Primary outcomeGeometric mean· Up to 48 hrs

T1/2 (Apparent Terminal Elimination Half-life)

GroupValue (hours)Spread
Bexagliflozin12.145.3
Bexagliflozin With Exenatide8.831.5
Primary outcomeGeometric mean· Up to 48 hrs

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

GroupValue (hr*ng/mL)Spread
Bexagliflozin776.027.5
Bexagliflozin With Exenatide1085.329.5
Secondary and other outcome results(1)
Secondary outcomeMean· 0-48 hours

Urinary Glucose Excretion (UGE)

GroupValue (g)Spread
Bexagliflozin0.070.140
Bexagliflozin With Exenatide0.050.100

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
BexagliflozinBexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose0 / 200 / 204 / 20
Bexagliflozin With ExenatideBexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose Exenatide: Byetta® (Exenatide), 10 µg, subcutaneous injection, twice a day (bid), two doses0 / 200 / 2010 / 20

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 65 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. 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. 2. Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive. 3. Subjects who were non-smokers for at least 3 months prior to screening. 4. Subjects with adequate venous access at multiple sites in both arms. 5. Subjects who were willing and able to be confined to the clinical research facility as required by the protocol. 6. Subjects who had the ability to comprehend and who were willing to provide written informed consent in accordance with institutional and regulatory guidelines. Exclusion Criteria: 1. 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. 2. Subjects with a clinically significant history of allergy to drugs or latex. 3. Subjects with a history of hypoglycemia. 4. Subjects with a history of alcohol or drug dependence in the last 12 months. 5. 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. 6. Subjects who used prescription or over-the-counter (OTC) drugs within 14 days prior to the first dose. 7. Subjects who used vitamin preparations or supplements (including St. John's Wort and ginseng) within 14 days prior to the first dose . 8. 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. 9. 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. 10. 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. 11. 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. 12. 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. 13. Subjects who had previously received bexagliflozin, or any other SGLT2 inhibitors within 3 months from the screening. 14. 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. 15. 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. 16. Subjects who had a positive result of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, urinary drug or urinary cotinine test. 17. Subjects with human immunodeficiency virus (HIV) infection. 18. Subjects who had had a febrile illness within 5 days prior to the first dose of study medication. 19. Subjects vaccinated within 30 days (with the exception of the flu vaccine) prior to the first dose of investigational drug. 20. Subjects with a history of acute or chronic pancreatitis or gall stones. 21. Positive urine glucose at screening. 22. Subjects with estimated glomerular filtration rate (eGFR) \<90 mL/min/1.73 m2 or a history of kidney transplant. 23. Subjects with digestion problems, including gastroesophageal reflux disease, irritable bowel syndrome, gastroparesis, and any other disorder deemed by the investigator to be clinically significant.

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