Clinical trial NCT03259789: Safety and Efficacy of Bexagliflozin Compared to Placebo as Add-on Therapy to Metformin in Type 2 Diabetes Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type2 Diabetes Mellitus
Lead sponsor: Theracos
Sponsor class: INDUSTRY
First posted: 2017-08-24
Enrollment: 351
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in HbA1c at Week 24 for Double-blind Group
timeFrame: Baseline to week 24
measure: Change From Baseline in HbA1c at Week 24 for High Glycemic Group
timeFrame: Baseline to week 24
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for Double-blind Group
timeFrame: Baseline, up to 24 weeks
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for High Glycemic Group
timeFrame: Baseline, up to 24 weeks
measure: Change From Baseline in Systolic Blood Pressure (SBP) at Week 24
timeFrame: Baseline to week 24
measure: Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group
timeFrame: Baseline, up to 24 weeks
measure: Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group
timeFrame: Baseline, up to 24 weeks
measure: Change in Body Mass From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2 for Double-blind Group
timeFrame: Baseline to week 24
measure: Change in Body Mass From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2 for High Glycemic Group
timeFrame: Baseline to week 24
measure: Change From Baseline in HbA1c Over Time in Double-blind Treatment Group
timeFrame: Baseline, up to 24 weeks
measure: Change in HbA1c Over Time Among Subjects Who Have Baseline HbA1c of > 10.5% and ≤ 12.0%
timeFrame: Baseline, up to 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Site 1232
state: Alabama
city: Birmingham
country: United States
facility: Clinical Research Site 1378
state: Alabama
city: Foley
country: United States
facility: Clinical Research Site 1269
state: Alabama
city: Little Rock
country: United States
facility: Clinical Research Site 1363
state: Arkansas
city: Anaheim
country: United States
facility: Clinical Research Site 1381
state: California
city: North Hollywood
country: United States
facility: Clinical Research Site 1375
state: California
city: Norwalk
country: United States
facility: Clinical Research Site 1365
state: California
city: Norwalk
country: United States
facility: Clinical Research Site 1382
state: Connecticut
city: Hollywood
country: United States
facility: Clinical Research Site 1372
state: Florida
city: Palm Springs
country: United States
facility: Clinical Research Site 1362
state: Florida
city: Pembroke Pines
country: United States
facility: Clinical Research Site 1373
state: Florida
city: Nampa
country: United States
facility: Clinical Research Site 1376
state: Idaho
city: Chicago
country: United States
facility: Clinical Research Site 1366
state: Illinois
city: New Orleans
country: United States
facility: Clinical Research Site 1294
state: Louisiana
city: Saint Louis
country: United States
facility: Clinical Research Site 1374
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Site 1370
state: Nevada
city: Berlin
country: United States
facility: Clinical Research Site 1009
state: New Jersey
city: Trenton
country: United States
facility: Clinical Research Site 1037
state: New Jersey
city: Albuquerque
country: United States
facility: Clinical Research Site 1286
state: New Mexico
city: Bronx
country: United States
facility: Clinical Research Site 1275
state: New York
city: New York
country: United States
facility: Clinical Research Site 1368
state: New York
city: Portland
country: United States
facility: Clinical Research Site 1019
state: Oregon
city: Gonzales
country: United States
facility: Clinical Research Site 1379
state: Texas
city: Houston
country: United States
facility: Clinical Research Site 1369
state: Texas
city: San Antonio
country: United States
facility: Clinical Research Site 1371
state: Texas
city: San Antonio
country: United States
facility: Clinical Research Site 1360
state: Texas
city: Nagoya
country: Japan
facility: Clinical Research Site 6048
state: Aichi
city: Sapporo
country: Japan
facility: Clinical Research Site 6050
state: Hokkaido
city: Koga
country: Japan
facility: Clinical Research Site 6041
state: Ibaraki
city: Atsugi
country: Japan
facility: Clinical Research Site 6029
state: Kanagawa
city: Kamakura
country: Japan
facility: Clinical Research Site 6051
state: Kanagawa
city: Yokohama
country: Japan
facility: Clinical Research Site 6020
state: Kanagawa
city: Tokyo
country: Japan
facility: Clinical Research Site 6055
state: Meguro
city: Higashiosaka
country: Japan
facility: Clinical Research Site 6046
state: Osaka
city: Kashiwara
country: Japan
facility: Clinical Research Site 6033
state: Osaka
city: Toyonaka
country: Japan
facility: Clinical Research Site 6013
state: Osaka
city: Kawaguchi
country: Japan
facility: Clinical Research Site 6052
state: Saitama
city: Shimotsuke
country: Japan
facility: Clinical Research Site 6053
state: Tochigi
city: Fukuoka
country: Japan
facility: Clinical Research Site 6040
city: Kyoto
country: Japan
facility: Clinical Research Site 6043
city: Osaka
country: Japan
facility: Clinical Research Site 6015
city: Tokyo
country: Japan
facility: Clinical Research Site 6045
city: Tokyo
country: Japan
facility: Clinical Research Site 6047
Study officials:
affiliation: Theracos
name: J, Paul Lock, M.D.
role: STUDY_DIRECTOR
References: