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

Type2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Bexagliflozin in Subjects With Type 2 Diabetes Mellitus Who Are Not Adequately Controlled by Metformin Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03259789
• Other study ID #: THR-1442-C-419
• Status: Completed
• Phase: Phase 3
• Start date: November 28, 2017
• Est. completion date: January 23, 2019

Study information

• Verified date: July 2021
• Source: Theracos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the effect of bexagliflozin compared to placebo as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in subjects with type 2 diabetes mellitus (T2DM).

Description:

Approximately 300 subjects with inadequately controlled T2DM on metformin were to be recruited from the United States and Japan. Subjects were randomly assigned to receive bexagliflozin tablets, 20 mg, or bexagliflozin tablets, placebo, in a ratio of 1:1 once daily for 24 weeks. Subjects were to continue taking metformin for the duration of the study. The study also enrolled 50 subjects with extremely poorly controlled T2DM on metformin to receive open-label bexagliflozin tablets, 20 mg, for 24 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 351
• Est. completion date: January 23, 2019
• Est. primary completion date: January 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

The subjects were required to meet the following criteria at the time of enrollment to be eligible for the study:

1. Had been age = 20 years at screening. Women of childbearing potential were required to have tested negative for pregnancy and have agreed to abstinence or contraception for the duration of the study to avoid any possible pregnancy. Females who were surgically sterile (hysterectomy, oophorectomy) or postmenopausal (absence of menses greater than 12 months) were eligible if they had tested negative for pregnancy at screening.

2. a) Had a history of T2DM with an HbA1c level of = 7.5% and = 10.5% at screening, or b) Had a history of T2DM with an HbA1c level of >10.5% and = 12.0% at screening

3. Had been prescribed a stable dose of metformin (=1500 mg per day in the US or = 1000 mg per day in Japan) as their sole anti-diabetic medication

4. Had a body mass index (BMI) = 45 kg m-2

5. Had been able to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines

6. Had no recent changes to their medications for hypertension or hyperlipidemia (if applicable)

7. Had the ability to regularly self-administer medication, as evidenced by consumption of all, or at worst one less than all, doses of run-in medication prior to randomization

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

1. Had a diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young

2. Were pregnant or breastfeeding

3. Had one or more hemoglobin alleles that affect HbA1c measurement

4. Had a history of genitourinary tract infection (e.g., UTI, GMI, vaginitis, balanitis) within 6 weeks of screening or a history of = 3 genitourinary infections requiring treatment within 6 months of screening

5. Had an estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), < 60 mL min-1 per 1.73 m2

6. Had a sitting systolic blood pressure >180 mmHg or a sitting diastolic blood pressure > 110 mmHg at screening

7. Had exposure to hypoglycemic agent(s) other than metformin during the 8 weeks prior to screening

8. Had a history of illicit drug use or alcohol abuse in the past 2 years

9. Had a life expectancy < 2 years

10. Had a diagnosis of New York Heart Association (NYHA) Class IV heart failure within 3 months of screening

11. Had experienced an MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening

12. Had exposure to an investigational drug within 30 days

13. Had a previous exposure to bexagliflozin or EGT0001474

14. Had a history of SGLT2 inhibitor treatment

15. Were participating in another interventional trial

16. Were not able to comply with the study scheduled visits

17. Had any condition, disease, disorder, or clinically relevant abnormality that, in the opinion of the primary investigator, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment

18. Had an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 × ULN or total bilirubin = 1.5 × ULN at screening

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

Drug:
• Bexagliflozin tablets, 20 mg
Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.
• Bexagliflozin tablets, placebo
Each subject will receive placebo (inactive tablet) once daily for the duration of the study.
• Bexagliflozin tablets, 20 mg
Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.

Locations

Country	Name	City	State
Japan	Clinical Research Site 6029	Atsugi	Kanagawa
Japan	Clinical Research Site 6040	Fukuoka
Japan	Clinical Research Site 6046	Higashiosaka	Osaka
Japan	Clinical Research Site 6051	Kamakura	Kanagawa
Japan	Clinical Research Site 6033	Kashiwara	Osaka
Japan	Clinical Research Site 6052	Kawaguchi	Saitama
Japan	Clinical Research Site 6041	Koga	Ibaraki
Japan	Clinical Research Site 6043	Kyoto
Japan	Clinical Research Site 6048	Nagoya	Aichi
Japan	Clinical Research Site 6015	Osaka
Japan	Clinical Research Site 6050	Sapporo	Hokkaido
Japan	Clinical Research Site 6053	Shimotsuke	Tochigi
Japan	Clinical Research Site 6045	Tokyo
Japan	Clinical Research Site 6047	Tokyo
Japan	Clinical Research Site 6055	Tokyo	Meguro
Japan	Clinical Research Site 6013	Toyonaka	Osaka
Japan	Clinical Research Site 6020	Yokohama	Kanagawa
United States	Clinical Research Site 1286	Albuquerque	New Mexico
United States	Clinical Research Site 1381	Anaheim	California
United States	Clinical Research Site 1009	Berlin	New Jersey
United States	Clinical Research Site 1232	Birmingham	Alabama
United States	Clinical Research Site 1378	Birmingham	Alabama
United States	Clinical Research Site 1275	Bronx	New York
United States	Clinical Research Site 1366	Chicago	Illinois
United States	Clinical Research Site 1269	Foley	Alabama
United States	Clinical Research Site 1379	Gonzales	Texas
United States	Clinical Research Site 1372	Hollywood	Florida
United States	Clinical Research Site 1369	Houston	Texas
United States	Clinical Research Site 1370	Las Vegas	Nevada
United States	Clinical Research Site 1363	Little Rock	Arkansas
United States	Clinical Research Site 1376	Nampa	Idaho
United States	Clinical Research Site 1294	New Orleans	Louisiana
United States	Clinical Research Site 1368	New York	New York
United States	Clinical Research Site 1375	North Hollywood	California
United States	Clinical Research Site 1365	Norwalk	California
United States	Clinical Research Site 1382	Norwalk	Connecticut
United States	Clinical Research Site 1362	Palm Springs	Florida
United States	Clinical Research Site 1373	Pembroke Pines	Florida
United States	Clinical Research Site 1019	Portland	Oregon
United States	Clinical Research Site 1374	Saint Louis	Missouri
United States	Clinical Research Site 1360	San Antonio	Texas
United States	Clinical Research Site 1371	San Antonio	Texas
United States	Clinical Research Site 1037	Trenton	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Theracos

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c at Week 24 for Double-blind Group	HbA1c was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.	Baseline to week 24
Primary	Change From Baseline in HbA1c at Week 24 for High Glycemic Group	The change in HbA1c from baseline at Week 24 in High Glycemic Group was calculated by subtracting the mean HbA1c at baseline from the mean HbA1c at Week 24	Baseline to week 24
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for Double-blind Group	FPG was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.	Baseline, up to 24 weeks
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for High Glycemic Group	The change in FPG from baseline at Week 24 for High Glycemic Group was calculated by subtracting the mean FPG at baseline from the mean FPG at Week 24	Baseline, up to 24 weeks
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) at Week 24	Changes from baseline at Week 24 in SBP for the double-blind group and high glycemic group	Baseline to week 24
Secondary	Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group	The proportion of subjects who achieved HbA1c < 7% at 6, 12, 18 and 24 weeks were calculated based on the number of subjects with a value at each time point for each group. The model-adjusted proportion was calculated based on a logistic analysis using Generalized Estimating Equation (GEE) logistic regression that includes country, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate. An unstructured correlation structure will be used, or autoregressive if the model with the unstructured structure does not converge.	Baseline, up to 24 weeks
Secondary	Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group	The proportion of subjects who achieved HbA1c < 7% at 6, 12, 18 and 24 weeks were calculated based on the number of subjects with a value at each time point for each group.	Baseline, up to 24 weeks
Secondary	Change in Body Mass From Baseline to Week 24 in Subjects With a BMI = 25 kg/m2 for Double-blind Group	Changes in body mass from baseline to week 24 was calculated based on LS means for both bexagliflozin and placebo groups.	Baseline to week 24
Secondary	Change in Body Mass From Baseline to Week 24 in Subjects With a BMI = 25 kg/m2 for High Glycemic Group	The change in body mass from baseline at week 24 for High Glycemic group was calculated by subtracting the mean body mass at baseline from the mean body mass at week 24	Baseline to week 24
Secondary	Change From Baseline in HbA1c Over Time in Double-blind Treatment Group	The change from baseline in HbA1c at 6, 12, 18 and 24 weeks was calculated based on the number of subjects with a value at each time point for each group. The model-adjusted change from baseline was calculated based on a mixed-effects repeated measures analysis that includes country, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.	Baseline, up to 24 weeks
Secondary	Change in HbA1c Over Time Among Subjects Who Have Baseline HbA1c of > 10.5% and = 12.0%	The change from baseline in HbA1c at 6, 12, 18 and 24 weeks was calculated based on the number of subjects with a value at each time point in High Glycemic Group.	Baseline, up to 24 weeks