Trial Outcomes & Findings for Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment (NCT NCT02836873)

Last Updated: 2021-06-30

Results Overview

The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with moderate renal impairment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

312 participants

Primary outcome timeframe

24 weeks

Results posted on

2021-06-30

Participant Flow

Participant milestones

Participant milestones
Measure	Bexagliflozin 20 mg Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Overall Study STARTED	157	155
Overall Study COMPLETED	152	144
Overall Study NOT COMPLETED	5	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Bexagliflozin 20 mg Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Overall Study Protocol Violation	0	1
Overall Study Adverse Event	1	4
Overall Study Withdrawal by Subject	2	2
Overall Study Lost to Follow-up	1	3
Overall Study Physician Decision	0	1
Overall Study Other	1	0

Baseline Characteristics

Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bexagliflozin 20 mg n=157 Participants Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=155 Participants Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.	Total n=312 Participants Total of all reporting groups
Age, Continuous	69.3 years STANDARD_DEVIATION 8.36 • n=5 Participants	69.9 years STANDARD_DEVIATION 8.29 • n=7 Participants	69.6 years STANDARD_DEVIATION 8.32 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	51 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	104 Participants n=7 Participants	196 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	17 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	149 Participants n=5 Participants	138 Participants n=7 Participants	287 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	61 Participants n=5 Participants	59 Participants n=7 Participants	120 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	83 Participants n=5 Participants	88 Participants n=7 Participants	171 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	53 participants n=5 Participants	50 participants n=7 Participants	103 participants n=5 Participants
Region of Enrollment Japan	58 participants n=5 Participants	58 participants n=7 Participants	116 participants n=5 Participants
Region of Enrollment France	12 participants n=5 Participants	16 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Spain	34 participants n=5 Participants	31 participants n=7 Participants	65 participants n=5 Participants
Height	164.8 cm STANDARD_DEVIATION 9.94 • n=5 Participants	164.7 cm STANDARD_DEVIATION 10.58 • n=7 Participants	164.8 cm STANDARD_DEVIATION 10.25 • n=5 Participants
Body Weight	82.90 kg STANDARD_DEVIATION 20.509 • n=5 Participants	82.59 kg STANDARD_DEVIATION 21.196 • n=7 Participants	82.75 kg STANDARD_DEVIATION 20.820 • n=5 Participants
BMI	30.29 kg/m^2 STANDARD_DEVIATION 5.988 • n=5 Participants	30.10 kg/m^2 STANDARD_DEVIATION 5.774 • n=7 Participants	30.20 kg/m^2 STANDARD_DEVIATION 5.874 • n=5 Participants
SBP Categories < 130 mm Hg	50 Participants n=5 Participants	42 Participants n=7 Participants	92 Participants n=5 Participants
SBP Categories > 130 mm Hg	107 Participants n=5 Participants	113 Participants n=7 Participants	220 Participants n=5 Participants
eGFR in Sub-group Stage 3a CKD: eGFR High Group	51.76 mL/min/1.73 m^2 STANDARD_DEVIATION 5.307 • n=5 Participants	51.27 mL/min/1.73 m^2 STANDARD_DEVIATION 4.404 • n=7 Participants	51.52 mL/min/1.73 m^2 STANDARD_DEVIATION 4.884 • n=5 Participants
eGFR in Sub-group Stage 3b CKD: eGFR Low Group	37.79 mL/min/1.73 m^2 STANDARD_DEVIATION 4.572 • n=5 Participants	37.87 mL/min/1.73 m^2 STANDARD_DEVIATION 4.629 • n=7 Participants	37.83 mL/min/1.73 m^2 STANDARD_DEVIATION 4.586 • n=5 Participants
Subjects in eGFR Sub-group at Baseline Stage 3a CKD: eGFR High Group	86 Participants n=5 Participants	80 Participants n=7 Participants	166 Participants n=5 Participants
Subjects in eGFR Sub-group at Baseline Stage 3b CKD: eGFR Low Group	71 Participants n=5 Participants	75 Participants n=7 Participants	146 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Outcome measures

Outcome measures
Measure	Bexagliflozin 20 mg n=157 Participants Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=155 Participants Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Change From Baseline in HbA1c at 24 Weeks	-0.59 percentage of glycated hemoglobin Standard Error 0.065	-0.31 percentage of glycated hemoglobin Standard Error 0.066

SECONDARY outcome

Timeframe: 24 weeks

Population: Only number of subjects with a value at baseline and at the specific visit is included.

A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in BMI from baseline to week 24 in subjects with a BMI ≥ 25 kg/m2.

Outcome measures

Outcome measures
Measure	Bexagliflozin 20 mg n=122 Participants Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=117 Participants Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Change in Body Weight From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2	-2.31 kg Standard Error 0.265	-0.55 kg Standard Error 0.269

SECONDARY outcome

Timeframe: 24 weeks

Population: Only number of subjects with a value at baseline and at Week 24 is included.

A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change from baseline in SBP to in subjects with baseline SBP ≥ 130 mm Hg at Week 24.

Outcome measures

Outcome measures
Measure	Bexagliflozin 20 mg n=104 Participants Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=108 Participants Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Change From Baseline in Systolic Blood Pressure (SBP) in Subjects With Baseline SBP ≥ 130 mm Hg at Week 24	-10.14 mm Hg Standard Error 1.477	-7.51 mm Hg Standard Error 1.460

SECONDARY outcome

Timeframe: 24 weeks

Population: Subjects who had the eGFR between 45 and 59 mL/min/1.73 m2 are included in this analysis.

A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3a CKD (eGFR 45 to 59 mL/min/1.73 m2) at week 24.

Outcome measures

Outcome measures
Measure	Bexagliflozin 20 mg n=86 Participants Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=80 Participants Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Change From Baseline in HbA1c in Subjects With Stage 3a CKD (eGFR 45 to 59 mL/Min/1.73 m2) at Week 24	-0.63 percentage of glycated hemoglobin Standard Error 0.086	-0.44 percentage of glycated hemoglobin Standard Error 0.089

SECONDARY outcome

Timeframe: 24 weeks

Population: Subjects with eGFR between 30 and 44 mL/min/1.73 m2 were included in this anlaysis.

A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3b CKD (eGFR 30 to 44 mL/min/1.73 m2) at week 24.

Outcome measures

Outcome measures
Measure	Bexagliflozin 20 mg n=71 Participants Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=75 Participants Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Change From Baseline in HbA1c in Subjects With Stage 3b CKD (eGFR 30 to 44 mL/Min/1.73 m2) at Week 24	-0.57 percentage of glycated hemoglobin Standard Error 0.100	-0.20 percentage of glycated hemoglobin Standard Error 0.097

Adverse Events

Bexagliflozin 20 mg

Serious events: 11 serious events

Other events: 56 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Bexagliflozin 20 mg n=157 participants at risk Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=155 participants at risk Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Renal and urinary disorders Polyuria	7.6% 12/157 • Number of events 15 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	4.5% 7/155 • Number of events 7 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Renal and urinary disorders Acute kidney injury	5.1% 8/157 • Number of events 9 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	3.9% 6/155 • Number of events 6 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Infections and infestations Nasopharyngitis	7.0% 11/157 • Number of events 13 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	8.4% 13/155 • Number of events 21 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Infections and infestations Urinary tract infection	6.4% 10/157 • Number of events 12 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	3.2% 5/155 • Number of events 5 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Infections and infestations Bronchitis	5.1% 8/157 • Number of events 8 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	1.3% 2/155 • Number of events 2 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 9/157 • Number of events 11 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	3.2% 5/155 • Number of events 5 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Gastrointestinal disorders Nausea	5.1% 8/157 • Number of events 9 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	7.1% 11/155 • Number of events 12 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Metabolism and nutrition disorders Hypoglycaemia	25.5% 40/157 • Number of events 258 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	25.8% 40/155 • Number of events 261 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).

Additional Information

Albert Collinson

Theracos Sub, LLC

Phone: (508) 630-2129

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI has no right to publish the trial results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Bexagliflozin 20 mg n=157 participants at risk Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Placebo n=155 participants at risk Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Ear and labyrinth disorders Deafness unilateral	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Hepatobiliary disorders Cholecystitis acute	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Metabolism and nutrition disorders Hypoglycemia	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Vascular disorders Orthostatic hypotension	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Cardiac disorders Bundle branch block left	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Cardiac disorders Cardiogenic shock	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Cardiac disorders Coronary artery disease	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Cardiac disorders Myocardial infarction	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Gastrointestinal disorders Gastritis erosive	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Gastrointestinal disorders Intestinal ischemia	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Gastrointestinal disorders Esophagitis	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Gastrointestinal disorders Pancreatitis acute	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma colon	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Infections and infestations Gastroenteritis	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Infections and infestations Lower respiratory tract infection	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Infections and infestations Sepsis	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Musculoskeletal and connective tissue disorders Arthralgia	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Musculoskeletal and connective tissue disorders Neuropathic anthropathy	0.00% 0/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.65% 1/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Nervous system disorders Carotid artery disease	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Nervous system disorders Cerebral infarction	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Respiratory, thoracic and mediastinal disorders Dyspnea exertional	0.64% 1/157 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).	0.00% 0/155 • Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).