Bexagliflozin Efficacy and Safety Trial

Type 2 Diabetes Mellitus Clinical Trial

— BEST  

Official title:

A Double Blind Placebo Controlled Study to Evaluate the Effects of Bexagliflozin on Hemoglobin A1c in Patients With Type 2 Diabetes and Increased Risk of Cardiovascular Adverse Events

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02558296
• Other study ID #: THR-1442-C-476
• Status: Completed
• Phase: Phase 3
• Start date: October 2015
• Est. completion date: October 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 in lowering hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM) and increased risk of cardiovascular adverse events.

The data from this study will be combined with the data from other bexagliflozin studies in a meta-analysis of CV safety outcomes.

Description:

Approximately 130 investigative sites globally are planned to participate in this study.

An estimated 1650 subjects with inadequately controlled T2DM and an elevated risk of cardiovascular adverse events will be randomized to bexagliflozin tablets, 20 mg, or placebo in a ratio of 2:1 in addition to the background anti-diabetic medications.

The study is an event-driven trial. The treatment period will end when the last randomized subject has completed at least 52 weeks of treatment and a total of at least 134 subjects have experienced a cardiac event.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1700
• Est. completion date: October 23, 2019
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Subjects with a diagnosis of T2DM

• Subjects who have had a stable treatment regimen for T2DM for the past 3 months

• Subjects who present with at least one of the following 3 histories:

Group 1: A history of atherosclerotic vascular disease Group 2: A history of heart failure Group 3: Age = 55 years with diabetes for = 10 years, uncontrolled hypertension, currently smoking, reduced kidney function, or cholesterol problems

Exclusion Criteria:

• Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young

• History of genitourinary tract infections

• Evidence of abnormal liver function

• History of MI, stroke or hospitalization for heart failure in the past 3 months

• Prior kidney transplant or evidence of kidney problems

• Prior or planned pace maker implantation

• Pregnant or nursing

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Bexagliflozin
20 mg, tablet
• Placebo
20 mg tablet to match active comparator

Locations

Country	Name	City	State
Canada	Research Site 5015	Cambridge	Ontario
Canada	Research Site 5008	Gatineau	Quebec
Canada	Research Site 5012	Hamilton	Ontario
Canada	Research Site 5023	London	Ontario
Canada	Research Site 5016	Peterborough	Ontario
Canada	Research Site 5006	Quebec
Canada	Research Site 5007	St-Charles-Borromee	Quebec
Canada	Research Site 5009	St. Georges	Quebec
Canada	Research Site 5005	Sudbury	Ontario
Canada	Research Site 5014	Toronto	Ontario
Canada	Research Site 5022	Toronto	Ontario
Canada	Research Site 5013	Vancouver	British Columbia
Czechia	Research Site 3116	Benesov
Czechia	Research Site 3106	Brandys nad Labem
Czechia	Research Site 3107	Brno
Czechia	Research Site 3118	Brno
Czechia	Research Site 3109	Cesky Krumlov
Czechia	Research Site 3114	Havirov
Czechia	Research Site 3103	Hradec Kralove
Czechia	Research Site 3110	Krnov
Czechia	Research Site 3102	Kromeriz
Czechia	Research Site 3105	Marianske Lazne
Czechia	Research Site 3113	Plzen
Czechia	Research Site 3104	Praha
Czechia	Research Site 3111	Praha
Czechia	Research Site 3112	Praha
Czechia	Research Site 3115	Uherske Hradiste
Denmark	Research Site 6103	Copenhagen
Denmark	Research Site 6104	Copenhagen
Denmark	Research Site 6105	Copenhagen
Korea, Republic of	Research Site 7004	Anyang	Gyeonggi-do
Korea, Republic of	Research Site 7006	Busan
Korea, Republic of	Research Site 7007	Chuncheon	Gangwon-Do
Korea, Republic of	Research Site 7005	Guri	Gyeonggi-do
Korea, Republic of	Research Site 7002	Gwangju
Korea, Republic of	Research Site 7008	Incheon
Korea, Republic of	Research Site 7001	Wonju	Gangwon-Do
Mexico	Research Site 2011	Aguascalientes
Mexico	Research Site 2009	Chihuahua
Mexico	Research Site 2013	Culiacan	Sinaloa
Mexico	Research Site 2015	Guadalajara	Jalisco
Mexico	Research Site 2012	Merida	Yucatan
Mexico	Research Site 2014	Mexico
Mexico	Research Site 2016	Queretaro
Mexico	Research Site 2008	Tampico	Tamaulipas
Mexico	Research Site 2010	Veracruz
Netherlands	Research Site 5110	Amsterdam
Netherlands	Research Site 5113	Harderwijk
Netherlands	Research Site 5101	Hertogenbosch
Netherlands	Research Site 5112	Hoofddorp
Netherlands	Research Site 5102	Hoogeveen
Netherlands	Research Site 5106	Rotterdam
Netherlands	Research Site 5103	Zwijndrecht
Poland	Research Site 7122	Aleksandrow Lodzki
Poland	Research Site 7113	Gdansk
Poland	Research Site 7119	Gdynia
Poland	Research Site 7109	Grodzisk Mazowiecki
Poland	Research Site 7106	Katowice
Poland	Research Site 7115	Katowice
Poland	Research Site 7121	Katowice
Poland	Research Site 7111	Kutno
Poland	Research Site 7104	Lodz
Poland	Research Site 7135	Lodz
Poland	Research Site 7120	Lublin
Poland	Research Site 7108	Olawa
Poland	Research Site 7118	Otwock
Poland	Research Site 7107	Pulawy
Poland	Research Site 7105	Sobotka
Poland	Research Site 7112	Sochaczew
Poland	Research Site 7123	Warsaw
Poland	Research Site 7116	Warszawa
Poland	Research Site 7117	Warszawa
Russian Federation	Research Site 9309	Lomonosov
Russian Federation	Research Site 9303	Moscow
Russian Federation	Research Site 9315	Moscow
Russian Federation	Research Site 9301	Novosibirsk
Russian Federation	Research Site 9314	Novosibirsk
Russian Federation	Research Site 9318	Novosibirsk
Russian Federation	Research Site 9304	Saint Petersburg
Russian Federation	Research Site 9307	Saint Petersburg
Russian Federation	Research Site 9310	Saint Petersburg
Russian Federation	Research Site 9311	Saint Petersburg
Russian Federation	Research Site 9312	Saint Petersburg
Russian Federation	Research Site 9302	Tomsk
Taiwan	Research Site 8001	Kaohsiung
Taiwan	Research Site 8002	New Taipei
Taiwan	Research Site 8006	Taichung
Taiwan	Research Site 8005	Tainan
Taiwan	Research Site 8003	Taipei
Taiwan	Research Site 8004	Taipei
Taiwan	Research Site 8007	Taipei
United States	Research Site 1044	Albuquerque	New Mexico
United States	Research Site 1043	Anderson	Indiana
United States	Research Site 1228	Annapolis	Maryland
United States	Research Site 1072	Augusta	Georgia
United States	Research Site 1225	Austin	Texas
United States	Research Site 1071	Avon	Indiana
United States	Research Site 1073	Azusa	California
United States	Research Site 1221	Baltimore	Maryland
United States	Research Site 1057	Boca Raton	Florida
United States	Research Site 1264	Bronx	New York
United States	Research Site 1059	Brooksville	Florida
United States	Research Site 1258	Champaign	Illinois
United States	Research Site 1085	Chapel Hill	North Carolina
United States	Research Site 1074	Charlotte	North Carolina
United States	Research Site 1076	Concord	California
United States	Research Site 1224	Covington	Kentucky
United States	Research Site 1042	Cumberland	Rhode Island
United States	Research Site 1259	Dallas	Texas
United States	Research Site 1218	Denver	Colorado
United States	Research Site 1086	Des Moines	Iowa
United States	Research Site 1075	Fargo	North Dakota
United States	Research Site 1078	Fresno	California
United States	Research Site 1090	Gilbert	Arizona
United States	Research Site 1092	Golden	Colorado
United States	Research Site 1089	Harbor City	California
United States	Research Site 1079	Hyattsville	Maryland
United States	Research Site 1252	Kalispell	Montana
United States	Research Site 1048	Kingwood	Texas
United States	Research Site 1070	Lampasas	Texas
United States	Research Site 1260	Lancaster	Pennsylvania
United States	Research Site 1080	Las Vegas	Nevada
United States	Research Site 1222	Lewisville	Texas
United States	Research Site 1058	Lincoln	California
United States	Research Site 1266	Lindsay	Oklahoma
United States	Research Site 1041	Little Rock	Arkansas
United States	Research Site 1004	Los Angeles	California
United States	Research Site 1051	Los Angeles	California
United States	Research Site 1223	Midland	Michigan
United States	Research Site 1068	Montclair	California
United States	Research Site 1056	Morehead City	North Carolina
United States	Research Site 1083	Newark	Delaware
United States	Research Site 1081	North Richland Hills	Texas
United States	Research Site 1216	Norwalk	Connecticut
United States	Research Site 1046	Oklahoma City	Oklahoma
United States	Research Site 1055	Oklahoma City	Oklahoma
United States	Research Site 1265	Oklahoma City	Oklahoma
United States	Research Site 1052	Omaha	Nebraska
United States	Research Site 1263	Omaha	Nebraska
United States	Research Site 1077	Orange	California
United States	Research Site 1050	Panama City	Florida
United States	Research Site 1217	Petoskey	Michigan
United States	Research Site 1082	Pocatello	Idaho
United States	Research Site 1099	Port Charlotte	Florida
United States	Research Site 1054	Saint Louis	Missouri
United States	Research Site 1060	Saint Louis	Missouri
United States	Research Site 1230	Salem	Virginia
United States	Research Site 1063	Salt Lake City	Utah
United States	Research Site 1053	San Antonio	Texas
United States	Research Site 1226	San Antonio	Texas
United States	Research Site 1220	Saratoga Springs	New York
United States	Research Site 1219	Somerset	New Jersey
United States	Research Site 1066	Tampa	Florida
United States	Research Site 1049	West Seneca	New York
United States	Research Site 1229	Wilmington	North Carolina
United States	Research Site 1064	Winston-Salem	North Carolina
United States	Research Site 1254	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Theracos

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Denmark,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in HbA1c From Baseline Over Time	To assess the effect of 20 mg bexagliflozin treatment on the change in HbA1c from baseline versus placebo over time up to 168 weeks	Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168
Other	Change in Fasting Plasma Glucose Over Time	To evaluate the effect of bexagliflozin treatment on the change in fasting plasma glucose (FPG) versus placebo over time up to 168 weeks	Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168
Other	Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification	To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period	24 week
Other	Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification	To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study period	Duration of study (168 weeks)
Other	Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent	To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period	24 weeks
Other	Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent	To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study	Duration of study (168 weeks)
Other	Proportion of Participants With Incidence of Hospitalization for Heart Failure	To measure the incidence of hospitalization for heart failure among all subjects and among subjects who have a history of heart failure at baseline	Duration of study (168 weeks)
Primary	Change in HbA1c From Baseline to Week 24	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 increased risk of cardiovascular adverse events.	24 weeks
Secondary	Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin	To evaluate the effect of 20 mg bexagliflozin on the change in HbA1c from baseline to week 24 in randomized subjects who have been prescribed insulin to control their diabetes	24 weeks
Secondary	Change in Body Weight From Baseline to Week 48	To evaluate the effect of 20 mg bexagliflozin on the change in body weight from baseline to week 48 in randomized subjects with a BMI = 25 kg/m2 compared to placebo	48 weeks
Secondary	Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline	To evaluate the effect of 20 mg bexagliflozin on the change in systolic blood pressure (SBP) from baseline to week 24 in subjects with baseline systolic blood pressure = 140 mmHg compared to placebo	24 weeks