Clinical trial NCT02820298: Study to Evaluate the Effects of a High-Fat Meal on Bexagliflozin in Healthy Subjects
Official title: A Phase 1, Open-label, Randomized, Two-period, Two-treatment, Crossover Study to Evaluate the Effect of A High-Fat Meal on the Pharmacokinetics of Bexagliflozin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Theracos
Sponsor class: INDUSTRY
First posted: 2016-06-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to investigate the effect of a high-fat meal on the levels of bexagliflozin in the blood in healthy subjects.

Detailed description: This was a single center, Phase 1, open-label, 2 × 2 crossover study designed to assess the effects of a high-fat meal on the PK of orally administered bexagliflozin tablets in 18 healthy adults. Subjects were randomized 1:1 to receive bexagliflozin tablets with a high-fat meal on day 1 and without a meal on day 8 after an overnight fast or to receive bexagliflozin tablets without a meal on day 1 after an overnight fast and with a high-fat meal on day 8.

Subjects were admitted to the clinic on the day before dosing in each treatment period, and stayed in the clinic until 48 h post-dose.

The subjects dosed in the fed state received an oral bexagliflozin tablet, 20 mg, 30 min after starting to consume a high-fat meal following an overnight fast. The meal was to be ingested in its entirety over an approximate 25-minute period, such that it was completed at least 5 minutes prior to the scheduled time of bexagliflozin dosing for the fed state treatment. Subjects dosed in the fasting state received an oral bexagliflozin tablet, 20 mg, after an overnight fast.

Blood samples for bexagliflozin plasma concentrations were collected at 0 h (pre-dose), and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose. Urine collection in 12 h batches was performed at pre-dose (-12 to 0 h on day 0 and day 7), and at post-dose (0 to 12 h, 12 to 24 h, 24 to 36 h, and 36 to 48 h) intervals.

Eligibility criteria: Each subject had to meet the following criteria to be eligible for the study:

1. Subjects who were between 18-65 years of age with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2.
2. Male subjects who were surgically sterile or male subjects who were not surgically sterile must have agreed to refrain from donating sperm and used appropriate birth control for a period of 30 days after discharge from the clinic.
3. Female subjects of childbearing potential who were willing to use an adequate method of contraception and to not become pregnant for the duration of the study.
4. Female subjects who were surgically sterile or postmenopausal were eligible if they tested negative on the urine pregnancy test.
5. Subjects who were non-smokers for at least 3 months prior to screening.
6. Subjects with adequate venous access at multiple sites in both arms.
7. Subjects who were willing and able to be confined to the clinical research facility as required by the Protocol.
8. Subjects who had the ability to comprehend and willingness to provide written informed consent in accordance with institutional and regulatory guidelines.

Subjects who met any of the following criteria were excluded from the study:

1. Subjects who were determined by the Investigator or sub-Investigator to be unsuitable for participating in the study based on medical conditions.
2. Female subjects who were nursing or pregnant.
3. Subjects with a clinically significant history of allergy to drugs or latex.
4. Subjects with a history of alcohol or drug dependence in the last 12 months.
5. Subjects who had 400 mL of whole blood collected within four months or 200 mL of whole blood collected within one month of the screening test.
6. Subjects who had blood component collection within 14 days prior to the screening test.
7. Subjects who had used prescription or over-the-counter drugs within 14 days prior to the first dose.
8. Subjects who had used vitamin preparations or supplements (including St. John's Wort and ginseng) within 14 days prior to the first dose.
9. Subjects who had undergone strenuous activity within 72 hours prior to Day 1 in each period.
10. Subjects who were unable (e.g., food intolerance) or unwilling to consume a high-fat breakfast within 25 minutes.
11. Subjects who had been treated with an investigational drug within 30 days or 7 half-lives of the investigational drug, whichever was longer, prior to the first dose of study drug in this trial.
12. Subjects who had previously received EGT0001474 or bexagliflozin, or any other SGLT2 inhibitors within 3 months from screening.
13. Subjects whose screening electrocardiogram (ECG) demonstrated any one of the following: heart rate \>100 bpm, QRS \>120 msec, QTc \>470 msec (corrected by Bazett's formula), PR \>220 msec (a subject with PR \>220 msec would generally be excluded but exceptions may have been allowed at the discretion of the Investigator), or any rhythm that was not sinus rhythm, sinus bradycardia, or sinus arrhythmia.
14. Subjects whose sitting blood pressure was above 140/90 mmHg at screening.
15. Subjects who had a positive result of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, urinary drug or urinary cotinine test.
16. Subjects with known human immunodeficiency virus (HIV) disease.
17. Subjects with abnormal vital signs, laboratory values, symptoms or signs that were deemed clinically significant by the Investigator.
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 prior to the first dose of medication.
20. Detectable urine glucose at screening (trace or greater).
21. Subjects with eGFR \<90 mL/min/1.73 m2 or a history of kidney transplant.
22. Subjects with digestion problems, including gastroesophageal reflux disease, irritable bowel syndrome, gastroparesis, and any other disorder deemed by the Investigator to be clinically significant.

Primary outcomes:
measure: Cmax (Maximum Observed Plasma Concentration)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose
measure: Tmax (Time of Maximum Observed Plasma Concentration)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose
measure: AUC0-t (Area Under the Plasma Concentration-time Curve From Time 0 to t)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose
measure: AUC0-∞ (Area Under the Plasma Concentration-time Curve From Time 0 to ∞)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose
measure: T1/2 (Apparent Terminal Elimination Half-life)
timeFrame: 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: Denver Clinical Research Unit
state: Colorado
Study officials:
affiliation: Davita Clinical Research
name: Robert Williams, M.D.
role: STUDY_DIRECTOR
References: