Trial Outcomes & Findings for Safety and Efficacy of Bexagliflozin in Subjects With Moderate Hepatic Impairment (NCT NCT03557658)
NCT ID: NCT03557658
Last Updated: 2021-06-03
Results Overview
Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
COMPLETED
PHASE1
16 participants
Up to 48 hours
2021-06-03
Participant Flow
Participant milestones
| Measure |
Normal Hepatic Function
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Number analyzed only include current and former smokers
Baseline characteristics by cohort
| Measure |
Normal Hepatic Function
n=8 Participants
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
n=8 Participants
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.1 years
STANDARD_DEVIATION 4.16 • n=8 Participants
|
59.9 years
STANDARD_DEVIATION 4.58 • n=8 Participants
|
58.5 years
STANDARD_DEVIATION 4.46 • n=16 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
4 Participants
n=16 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
12 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
14 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=16 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
15 Participants
n=16 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=16 Participants
|
|
Child-Pugh Total Score
|
0 scores on a scale
STANDARD_DEVIATION 0 • n=8 Participants
|
8.3 scores on a scale
STANDARD_DEVIATION 0.89 • n=8 Participants
|
4.13 scores on a scale
STANDARD_DEVIATION 4.30 • n=16 Participants
|
|
Smoking Status
Current Smoker
|
2 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
4 Participants
n=16 Participants
|
|
Smoking Status
Former Smoker
|
3 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
6 Participants
n=16 Participants
|
|
Smoking Status
Non-Smoker
|
3 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
6 Participants
n=16 Participants
|
|
Pack Years of Cigarette Smoking
|
5.2 years
STANDARD_DEVIATION 5.27 • n=5 Participants • Number analyzed only include current and former smokers
|
13.2 years
STANDARD_DEVIATION 20.09 • n=5 Participants • Number analyzed only include current and former smokers
|
9.23 years
STANDARD_DEVIATION 14.47 • n=10 Participants • Number analyzed only include current and former smokers
|
PRIMARY outcome
Timeframe: Up to 48 hoursPopulation: The Pharmacokinetic (PK) population included all subjects without major protocol violations who were dispensed the study drug and provided an observation for at least one primary PK endpoint.
Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
n=8 Participants
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
|---|---|---|
|
Cmax (Maximum Observed Plasma Concentration)
Total Bexagliflozin
|
90.8 ng/mL
Geometric Coefficient of Variation 34.0
|
96.5 ng/mL
Geometric Coefficient of Variation 37.3
|
|
Cmax (Maximum Observed Plasma Concentration)
Unbound Bexagliflozin
|
6.0 ng/mL
Geometric Coefficient of Variation 45.5
|
6.6 ng/mL
Geometric Coefficient of Variation 46.6
|
PRIMARY outcome
Timeframe: Up to 48 hoursPopulation: PK population
Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
n=8 Participants
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
|---|---|---|
|
Tmax (Time of Maximum Observed Plasma Concentration)
Total Bexagliflozin
|
3.00 hours
Interval 2.0 to 3.05
|
3.00 hours
Interval 2.0 to 3.0
|
|
Tmax (Time of Maximum Observed Plasma Concentration)
Unbound Bexagliflozin
|
3.00 hours
Interval 2.0 to 3.05
|
3.00 hours
Interval 2.0 to 3.05
|
PRIMARY outcome
Timeframe: Up to 48 hoursPopulation: The adjusted r2 value for the regression for Subject 4551383007 (normal hepatic function group) was less than 0.7. The T1/2 was not estimated.
Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
n=8 Participants
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
|---|---|---|
|
T1/2 (Apparent Terminal Elimination Half-life)
Total Bexagliflozin
|
9.4 hours
Geometric Coefficient of Variation 40.2
|
9.5 hours
Geometric Coefficient of Variation 51.0
|
|
T1/2 (Apparent Terminal Elimination Half-life)
Unbound Bexagliflozin
|
11.3 hours
Geometric Coefficient of Variation 44.1
|
10.6 hours
Geometric Coefficient of Variation 37.7
|
PRIMARY outcome
Timeframe: Up to 48 hoursPopulation: The adjusted r2 value for the regression for Subject 4551383007 (normal hepatic function group) was less than 0.7. The AUC0-inf was not estimated.
Whole venous blood samples of 6mL were collected from a peripheral vein prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
n=8 Participants
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
|---|---|---|
|
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Total Bexagliflozin
|
695.8 ng*h/mL
Geometric Coefficient of Variation 25.3
|
893.0 ng*h/mL
Geometric Coefficient of Variation 32.2
|
|
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Unbound Bexagliflozin
|
47.9 ng*h/mL
Geometric Coefficient of Variation 31.0
|
63.3 ng*h/mL
Geometric Coefficient of Variation 38.9
|
PRIMARY outcome
Timeframe: 0-48 hoursPopulation: The Pharmacodynamic (PD) Population included all subjects without major protocol violations who were dispensed the study drug and produced at least the first 12 h post-dose urine. The PD Population was used to summarize the PD parameters. One subject in the Normal Hepatic Function group did not have the urinary glucose concentration measurement on the 36 to 48-hour urine collection.
Pre-dose urine samples were collected from -12 to 0 h for baseline measurement of pharmacodynamic parameters. Post-dose urine samples were collected without preservative in four batches: 0 to 12 h, 12 to 24 h, 24 to 36h, and 36 to 48 h after dosing. Urine aliquots were prepared from well mixed collections for the assessment of pharmacodynamics.
Outcome measures
| Measure |
Normal Hepatic Function
n=8 Participants
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
n=8 Participants
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
|---|---|---|
|
Urinary Glucose Excretion 0-48 Hours
Pre-dose (-12 - 0 hours)
|
0.04 g
Standard Deviation 0.045
|
0.91 g
Standard Deviation 2.464
|
|
Urinary Glucose Excretion 0-48 Hours
0 - 12 hours post-dose
|
37.76 g
Standard Deviation 7.253
|
29.57 g
Standard Deviation 8.492
|
|
Urinary Glucose Excretion 0-48 Hours
12 - 24 hours post-dose
|
21.99 g
Standard Deviation 5.780
|
19.25 g
Standard Deviation 6.311
|
|
Urinary Glucose Excretion 0-48 Hours
24 - 36 hours post-dose
|
26.76 g
Standard Deviation 14.588
|
20.96 g
Standard Deviation 11.340
|
|
Urinary Glucose Excretion 0-48 Hours
36 - 48 hours post-dose
|
5.87 g
Standard Deviation 4.785
|
5.11 g
Standard Deviation 5.165
|
|
Urinary Glucose Excretion 0-48 Hours
0 - 24 hours post-dose
|
59.75 g
Standard Deviation 12.497
|
48.82 g
Standard Deviation 12.405
|
|
Urinary Glucose Excretion 0-48 Hours
0 - 48 hours post-dose
|
91.92 g
Standard Deviation 28.142
|
74.89 g
Standard Deviation 25.410
|
Adverse Events
Normal Hepatic Function
Moderate Hepatic Impairment
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Normal Hepatic Function
n=8 participants at risk
Healthy subjects with normal hepatic function. Each subject will receive a single oral dose of bexagliflozin, 20 mg.
|
Moderate Hepatic Impairment
n=8 participants at risk
Subjects with hepatic impairment conforming to the Child-Pugh class B (total score 7-9). Each subject will receive a single oral dose of bexagliflozin tablet, 20 mg
|
|---|---|---|
|
General disorders
Feeling abnormal
|
12.5%
1/8 • Number of events 1 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
0.00%
0/8 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
|
General disorders
Fatigue
|
0.00%
0/8 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
12.5%
1/8 • Number of events 1 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
|
General disorders
Vessel puncture site haemorrhage
|
0.00%
0/8 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
12.5%
1/8 • Number of events 1 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
|
Infections and infestations
Pneumonia
|
0.00%
0/8 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
12.5%
1/8 • Number of events 1 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.5%
1/8 • Number of events 1 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
0.00%
0/8 • The adverse event data were collected from Day 0 up to Day 16 after drug administration
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Investigator does not have the right to publish trial results.
- Publication restrictions are in place
Restriction type: OTHER