Trial Outcomes & Findings for Bexagliflozin Drug/Drug Interaction Study With Exenatide Injection (NCT NCT03167411)

NCT ID: NCT03167411

Last Updated: 2021-05-28

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

Up to 48 hrs

Results posted on

2021-05-28

Participant Flow

20 healthy subjects were randomly assigned to one of the two groups (1 or 2) and will receive both treatments alternately, in a crossover fashion (two-period, two-treatment crossover design), with the two treatment groups separated by a 7-day washout period.

Participant milestones

Participant milestones
Measure	Bexagliflozin, Then Bexagliflozin With Exenatide After an overnight fast, subjects received a single oral dose of bexagliflozin tablets, 20 mg alone 30 min before breakfast. After a washout period of 7 days, the subjects then received a subcutaneous injection of exenatide 10 µg at 30 min prior to a single oral dose of bexagliflozin, and 1 hr before breakfast and followed by the second dose of exenatide alone 1 hr prior to the evening meal.	Bexagliflozin With Exenatide, Then Bexagliflozin Alone Subjects received a subcutaneous injection of exenatide at 10 µg twice a day (bid) with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast, followed by the second dose of exenatide alone 1 hr prior to the evening meal. After a washout period of 7 days, the subjects then received a single oral dose of bexagliflozin tablets, 20 mg alone 30 min before breakfast.
Overall Study STARTED	10	10
Overall Study COMPLETED	10	9
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Bexagliflozin, Then Bexagliflozin With Exenatide After an overnight fast, subjects received a single oral dose of bexagliflozin tablets, 20 mg alone 30 min before breakfast. After a washout period of 7 days, the subjects then received a subcutaneous injection of exenatide 10 µg at 30 min prior to a single oral dose of bexagliflozin, and 1 hr before breakfast and followed by the second dose of exenatide alone 1 hr prior to the evening meal.	Bexagliflozin With Exenatide, Then Bexagliflozin Alone Subjects received a subcutaneous injection of exenatide at 10 µg twice a day (bid) with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast, followed by the second dose of exenatide alone 1 hr prior to the evening meal. After a washout period of 7 days, the subjects then received a single oral dose of bexagliflozin tablets, 20 mg alone 30 min before breakfast.
Overall Study Adverse Event	0	1

Baseline Characteristics

Bexagliflozin Drug/Drug Interaction Study With Exenatide Injection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bexagliflozin, Then Bexagliflozin With Exenatide n=10 Participants After an overnight fast, subjects received a single oral dose of bexagliflozin tablets, 20 mg alone 30 min before breakfast. After a washout period of 7 days, the subjects then received a subcutaneous injection of exenatide 10 µg at 30 min prior to a single oral dose of bexagliflozin, and 1 hr before breakfast and followed by the second dose of exenatide alone 1 hr prior to the evening meal.	Bexagliflozin With Exenatide, Then Bexagliflozin n=10 Participants Subjects received a subcutaneous injection of exenatide at 10 µg twice a day (bid) with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast, followed by the second dose of exenatide alone 1 hr prior to the evening meal. After a washout period of 7 days, the subjects then received a single oral dose of bexagliflozin tablets, 20 mg alone 30 min before breakfast.	Total n=20 Participants Total of all reporting groups
Age, Continuous	35.0 years STANDARD_DEVIATION 9.03 • n=5 Participants	43.1 years STANDARD_DEVIATION 14.79 • n=7 Participants	39.1 years STANDARD_DEVIATION 12.63 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	77.6 kg STANDARD_DEVIATION 10.48 • n=5 Participants	80.7 kg STANDARD_DEVIATION 17.29 • n=7 Participants	79.1 kg STANDARD_DEVIATION 14.01 • n=5 Participants
Height	173.1 cm STANDARD_DEVIATION 9.66 • n=5 Participants	170.8 cm STANDARD_DEVIATION 10.94 • n=7 Participants	172.0 cm STANDARD_DEVIATION 10.11 • n=5 Participants
BMI	25.9 kg/m^2 STANDARD_DEVIATION 3.45 • n=5 Participants	27.3 kg/m^2 STANDARD_DEVIATION 3.14 • n=7 Participants	26.6 kg/m^2 STANDARD_DEVIATION 3.29 • n=5 Participants
Systolic Blood Pressure	109.1 mm Hg STANDARD_DEVIATION 11.98 • n=5 Participants	106.3 mm Hg STANDARD_DEVIATION 8.11 • n=7 Participants	107.7 mm Hg STANDARD_DEVIATION 10.06 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 48 hrs

Population: Number of subjects in the PK population with data

Outcome measures

Outcome measures
Measure	Bexagliflozin n=19 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose	Bexagliflozin With Exenatide n=17 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose Exenatide: Byetta® (Exenatide), 10 µg, subcutaneous injection, twice a day (bid), two doses
Cmax (Maximum Observed Plasma Concentration)	95.9 ng/mL Geometric Coefficient of Variation 33.6	121.6 ng/mL Geometric Coefficient of Variation 33.1

PRIMARY outcome

Timeframe: Up to 48 hrs

Population: Number of subjects in the PK population with data

Outcome measures

Outcome measures
Measure	Bexagliflozin n=19 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose	Bexagliflozin With Exenatide n=17 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose Exenatide: Byetta® (Exenatide), 10 µg, subcutaneous injection, twice a day (bid), two doses
Tmax (Time of Maximum Observed Plasma Concentration)	2.00 hours Interval 1.0 to 5.0	5.00 hours Interval 2.0 to 10.0

PRIMARY outcome

Timeframe: Up to 48 hrs

Population: Number of subjects in the PK population with data

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.

Outcome measures

Outcome measures
Measure	Bexagliflozin n=16 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose	Bexagliflozin With Exenatide n=16 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose Exenatide: Byetta® (Exenatide), 10 µg, subcutaneous injection, twice a day (bid), two doses
T1/2 (Apparent Terminal Elimination Half-life)	12.1 hours Geometric Coefficient of Variation 45.3	8.8 hours Geometric Coefficient of Variation 31.5

PRIMARY outcome

Timeframe: Up to 48 hrs

Population: Number of subjects in the PK population with data

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.

Outcome measures

Outcome measures
Measure	Bexagliflozin n=16 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose	Bexagliflozin With Exenatide n=16 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose Exenatide: Byetta® (Exenatide), 10 µg, subcutaneous injection, twice a day (bid), two doses
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)	776.0 hr*ng/mL Geometric Coefficient of Variation 27.5	1085.3 hr*ng/mL Geometric Coefficient of Variation 29.5

SECONDARY outcome

Timeframe: 0-48 hours

Population: Number of subjects in the PD population with data in the specific category

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.

Outcome measures

Outcome measures
Measure	Bexagliflozin n=19 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose	Bexagliflozin With Exenatide n=17 Participants Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose Exenatide: Byetta® (Exenatide), 10 µg, subcutaneous injection, twice a day (bid), two doses
Urinary Glucose Excretion (UGE) 0 - 24 hours	65.21 g Standard Deviation 15.035	55.65 g Standard Deviation 12.123
Urinary Glucose Excretion (UGE) Pre-dose (-12 to 0 hours)	0.07 g Standard Deviation 0.140	0.05 g Standard Deviation 0.100
Urinary Glucose Excretion (UGE) 0 - 12 hours	38.32 g Standard Deviation 8.705	26.38 g Standard Deviation 8.347
Urinary Glucose Excretion (UGE) 12 - 24 hours	26.89 g Standard Deviation 7.833	28.95 g Standard Deviation 6.812
Urinary Glucose Excretion (UGE) 24 - 36 hours	21.93 g Standard Deviation 6.934	22.16 g Standard Deviation 6.845
Urinary Glucose Excretion (UGE) 36 - 48 hours	9.56 g Standard Deviation 6.283	9.21 g Standard Deviation 6.499
Urinary Glucose Excretion (UGE) 0 - 48 hours	96.70 g Standard Deviation 25.080	88.11 g Standard Deviation 20.525

Adverse Events

Bexagliflozin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Bexagliflozin With Exenatide

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Bexagliflozin n=20 participants at risk Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose	Bexagliflozin With Exenatide n=20 participants at risk Bexagliflozin: Bexagliflozin tablets, 20 mg, oral, one dose Exenatide: Byetta® (Exenatide), 10 µg, subcutaneous injection, twice a day (bid), two doses
Gastrointestinal disorders Abdominal pain	0.00% 0/20 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.
Gastrointestinal disorders Vomiting	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.	20.0% 4/20 • Number of events 4 • Adverse event data was collected from Day 0 to Day 10.
Gastrointestinal disorders Nausea	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.	35.0% 7/20 • Number of events 7 • Adverse event data was collected from Day 0 to Day 10.
General disorders Asthenia	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.	0.00% 0/20 • Adverse event data was collected from Day 0 to Day 10.
General disorders Fatigue	0.00% 0/20 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.
Injury, poisoning and procedural complications Laceration	0.00% 0/20 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.
Nervous system disorders Dizziness	0.00% 0/20 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.
Nervous system disorders Paresthesia	0.00% 0/20 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.
Nervous system disorders Headache	10.0% 2/20 • Number of events 2 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.
Renal and urinary disorders Pollakiuria	10.0% 2/20 • Number of events 2 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.
Vascular disorders Hot flush	0.00% 0/20 • Adverse event data was collected from Day 0 to Day 10.	5.0% 1/20 • Number of events 1 • Adverse event data was collected from Day 0 to Day 10.

Additional Information

Albert Collinson

Theracos Sub, LLC

Phone: (508) 630-2129

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place