Trial Outcomes & Findings for Safety and Efficacy of Bexagliflozin Compared to Sitagliptin as Add-on Therapy to Metformin in Type 2 Diabetes Subjects (NCT NCT03115112)

Last Updated: 2021-06-22

Results Overview

The primary efficacy objective is to demonstrate that bexagliflozin is non-inferior to sitagliptin by evaluating the treatment effect on hemoglobin A1c (HbA1c) reduction at week 24 in subjects whose type 2 diabetes mellitus (T2DM) is inadequately controlled by metformin.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

386 participants

Primary outcome timeframe

Baseline to week 24

Results posted on

2021-06-22

Participant Flow

Participant milestones

Participant milestones
Measure	Bexagliflozin Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study. Bexagliflozin: 20 mg, tablet Placebo for sitagliptin: 100 mg inactive tablet to match active comparator	Sitagliptin Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Sitagliptin: 100 mg, tablet Placebo for bexagliflozin: 20 mg inactive tablet to match active comparator
Overall Study STARTED	192	194
Overall Study Intention-to-treat	191	193
Overall Study COMPLETED	180	189
Overall Study NOT COMPLETED	12	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Bexagliflozin Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study. Bexagliflozin: 20 mg, tablet Placebo for sitagliptin: 100 mg inactive tablet to match active comparator	Sitagliptin Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Sitagliptin: 100 mg, tablet Placebo for bexagliflozin: 20 mg inactive tablet to match active comparator
Overall Study Adverse Event	5	1
Overall Study Withdrawal by Subject	4	2
Overall Study Lost to Follow-up	0	1
Overall Study Death	1	0
Overall Study Pregnancy	1	0
Overall Study Site closure	1	1

Baseline Characteristics

Safety and Efficacy of Bexagliflozin Compared to Sitagliptin as Add-on Therapy to Metformin in Type 2 Diabetes Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bexagliflozin n=191 Participants Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study.	Sitagliptin n=193 Participants Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study.	Total n=384 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 9.69 • n=5 Participants	59.6 years STANDARD_DEVIATION 9.76 • n=7 Participants	59.4 years STANDARD_DEVIATION 9.72 • n=5 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	67 Participants n=7 Participants	138 Participants n=5 Participants
Sex: Female, Male Male	120 Participants n=5 Participants	126 Participants n=7 Participants	246 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	188 Participants n=5 Participants	186 Participants n=7 Participants	374 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	27 Participants n=5 Participants	35 Participants n=7 Participants	62 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	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	158 Participants n=5 Participants	156 Participants n=7 Participants	314 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Hungary	33 participants n=5 Participants	23 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment Czechia	16 participants n=5 Participants	25 participants n=7 Participants	41 participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	21 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment Japan	27 participants n=5 Participants	35 participants n=7 Participants	62 participants n=5 Participants
Region of Enrollment Poland	70 participants n=5 Participants	44 participants n=7 Participants	114 participants n=5 Participants
Region of Enrollment Spain	30 participants n=5 Participants	45 participants n=7 Participants	75 participants n=5 Participants
Height	167.4 cm STANDARD_DEVIATION 10.67 • n=5 Participants	168.3 cm STANDARD_DEVIATION 9.63 • n=7 Participants	167.9 cm STANDARD_DEVIATION 10.16 • n=5 Participants
Body Weight	90.27 kg STANDARD_DEVIATION 20.736 • n=5 Participants	89.44 kg STANDARD_DEVIATION 19.235 • n=7 Participants	89.85 kg STANDARD_DEVIATION 19.974 • n=5 Participants
BMI	32.06 kg/m^2 STANDARD_DEVIATION 6.052 • n=5 Participants	31.39 kg/m^2 STANDARD_DEVIATION 5.294 • n=7 Participants	31.72 kg/m^2 STANDARD_DEVIATION 5.686 • n=5 Participants
HbA1c	7.94 percentage of glycated hemoglobin STANDARD_DEVIATION 0.808 • n=5 Participants	8.03 percentage of glycated hemoglobin STANDARD_DEVIATION 0.921 • n=7 Participants	7.99 percentage of glycated hemoglobin STANDARD_DEVIATION 0.867 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to week 24

Population: Subjects in the intention-to-treat population and with a value at baseline and at week 24 were included.

Outcome measures

Outcome measures
Measure	Bexagliflozin n=180 Participants Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study. Bexagliflozin: 20 mg, tablet Placebo for sitagliptin: 100 mg inactive tablet to match active comparator	Sitagliptin n=190 Participants Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Sitagliptin: 100 mg, tablet Placebo for bexagliflozin: 20 mg inactive tablet to match active comparator
Change in HbA1c From Baseline to Week 24	-0.74 percentage of HbA1c Interval -0.86 to -0.62	-0.82 percentage of HbA1c Interval -0.93 to -0.71

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Subjects in the intention-to-treat population and with values at baseline and at week 24 were included.

To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in fasting plasma glucose (FPG) at week 24

Outcome measures

Outcome measures
Measure	Bexagliflozin n=180 Participants Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study. Bexagliflozin: 20 mg, tablet Placebo for sitagliptin: 100 mg inactive tablet to match active comparator	Sitagliptin n=190 Participants Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Sitagliptin: 100 mg, tablet Placebo for bexagliflozin: 20 mg inactive tablet to match active comparator
Change in FPG From Baseline at Week 24	-1.82 mmol/L Interval -2.09 to -1.55	-1.45 mmol/L Interval -1.7 to -1.19

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Subjects in the intention-to-treat population with a baseline body mass index \>= 25 kg/m2 and had body weight values at baseline and at week 24 were included in the analysis.

To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in body weight in subjects with baseline body mass index (BMI) ≥ 25 kg/m2 at week 24

Outcome measures

Outcome measures
Measure	Bexagliflozin n=158 Participants Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study. Bexagliflozin: 20 mg, tablet Placebo for sitagliptin: 100 mg inactive tablet to match active comparator	Sitagliptin n=171 Participants Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Sitagliptin: 100 mg, tablet Placebo for bexagliflozin: 20 mg inactive tablet to match active comparator
Change in Body Weight in Subjects With Baseline BMI ≥ 25 kg/m2 at Week 24	-3.35 kg Interval -3.85 to -2.84	-0.81 kg Interval -1.29 to -0.32

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Subjects in the intention-to-treat population with values at baseline and at week 24 were included.

To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in systolic blood pressure (SBP) in subjects at week 24

Outcome measures

Outcome measures
Measure	Bexagliflozin n=180 Participants Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study. Bexagliflozin: 20 mg, tablet Placebo for sitagliptin: 100 mg inactive tablet to match active comparator	Sitagliptin n=190 Participants Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Sitagliptin: 100 mg, tablet Placebo for bexagliflozin: 20 mg inactive tablet to match active comparator
Change in SBP in Subjects From Baseline at Week 24	-4.23 mm Hg Interval -6.18 to -2.28	-1.90 mm Hg Interval -3.75 to -0.06

Adverse Events

Bexagliflozin

Serious events: 7 serious events

Other events: 28 other events

Deaths: 1 deaths

Sitagliptin

Serious events: 4 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bexagliflozin n=191 participants at risk Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study.	Sitagliptin n=193 participants at risk Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study.
Cardiac disorders Atrial fibrillation	0.52% 1/191 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.00% 0/193 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Cardiac disorders Cardiac failure	0.00% 0/191 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.52% 1/193 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Cardiac disorders Microvascular coronary artery disease	0.52% 1/191 • Number of events 2 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.00% 0/193 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Infections and infestations Anal abscess	0.52% 1/191 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.00% 0/193 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Infections and infestations Gangrene	0.52% 1/191 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.00% 0/193 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Musculoskeletal and connective tissue disorders Osteoarthritis	1.0% 2/191 • Number of events 2 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.00% 0/193 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Blood and lymphatic system disorders Anemia	0.00% 0/191 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.52% 1/193 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Gastrointestinal disorders Gallstone ileus	0.00% 0/191 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.52% 1/193 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Gastrointestinal disorders Intestinal obstruction	0.00% 0/191 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.52% 1/193 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.52% 1/191 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.00% 0/193 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Nervous system disorders Intracranial aneursym	0.00% 0/191 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.52% 1/193 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/191 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	0.52% 1/193 • Number of events 1 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)

Other adverse events

Other adverse events
Measure	Bexagliflozin n=191 participants at risk Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study.	Sitagliptin n=193 participants at risk Subjects will receive a sitagliptin tablet, 100 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study.
Infections and infestations Nasopharyngitis	7.9% 15/191 • Number of events 15 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	13.0% 25/193 • Number of events 29 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Infections and infestations Influenza	1.6% 3/191 • Number of events 3 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	5.2% 10/193 • Number of events 10 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Infections and infestations Urinary tract infection	3.7% 7/191 • Number of events 9 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	2.1% 4/193 • Number of events 4 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)
Metabolism and nutrition disorders Hypoglycemia	3.1% 6/191 • Number of events 12 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)	5.2% 10/193 • Number of events 14 • Adverse event data were collected from 1 week prior to randomization (V2) until Week 26 (V8/follow up visit)

Additional Information

Albert Collinson

Theracos Sub, LLC

Phone: (508) 630-2129

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER