Clinical trial NCT02715258: Safety and Efficacy of Bexagliflozin as Monotherapy in Patients With Type 2 Diabetes
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Compare the Efficacy and Safety of Bexagliflozin to Placebo in Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Theracos
Sponsor class: INDUSTRY
First posted: 2016-03-22
Enrollment: 210
Sex: ALL
Minimum age (years): 18
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 in lowering hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM).

Detailed description: This was a phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of once daily oral administration of bexagliflozin tablets, 20 mg or placebo tablets, in male and female subjects with T2DM who were treatment-naïve or previously treated with 1 oral hypoglycemic agent (OHA).

Prospective subjects being treated with one OHA were eligible if they had an HbA1c between 6.5% and 10.0% and were willing to complete a 6-week washout. Individuals taking thiazolidinediones were not eligible for the study. All eligible subjects were to start a 2-week placebo run-in period. Subjects who missed no more than 1 dose of the run-in medication, had fasting blood glucose values ≥ 250 mg/dL on no more than two consecutive days, and had an HbA1c level between 7.0% and 10.5% and a fasting glucose level \< 250 mg/dL after the run-in period were eligible for randomization.

Two hundred and ten (210) subjects were planned to be randomly assigned to receive oral bexagliflozin tablets, 20 mg or placebo, in a 2:1 ratio once daily for 24 weeks. Subjects with uncontrolled hyperglycemia based on blood glucose levels could receive additional approved anti-diabetic medications. Treatment group assignment at the start of the treatment period was stratified by baseline HbA1c level and background anti-diabetes treatment status (treatment naïve or not).

Each subject was contacted by telephone at week 2 and was instructed to return to the clinic at weeks 6, 12, 18, and 24 for efficacy assessment and safety monitoring. Subjects returned to the clinic for a follow-up visit at week 26 or 2 weeks after the last dose of investigational product if the subject terminated prior to week 24.

Eligibility criteria: The study population included:

1. Male or female adult subjects ≥ 18 years of age at screening
2. Subjects who were treatment naïve or receiving 1 OHA in combination with diet and exercise
3. Subjects with a diagnosis of T2DM
4. Subjects with HbA1c levels at screening between 7.0% and 10.5% (inclusive) if treatment-naïve or with HbA1c levels between 6.5 and 10.0% (inclusive) if on 1 oral anti diabetic agent
5. Subjects with a BMI ≤ 45 kg/m2
6. Subjects whose doses of medications for hypertension or hyperlipidemia (if applicable) had not changed for at least 30 days prior to screening
7. Subjects who were willing and able to return for all clinic visits and to complete all study required procedures
8. Female subjects of childbearing potential who were willing to use an adequate method of contraception and not become pregnant for the duration of the study.
9. Subjects who maintained glycemic control throughout washout, if applicable.
10. Subjects who had HbA1c levels between 7.0 and 10.5% prior to randomization
11. Subjects who had been compliant in investigational product administration by missing no more than 1 dose of run-in medication

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

1. A diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young
2. Use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor agonist therapy) or thiazolidinedione class drugs at the time of screening
3. Female subjects who were pregnant or breastfeeding
4. Hemoglobinopathy or carrier status for hemoglobin alleles that affected HbA1c measurement
5. Genitourinary tract infection (e.g., UTI, GMI, vaginitis, balanitis) within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within 6 months from screening
6. Estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), \< 60 mL/min/1.73 m2 at screening
7. Uncontrolled hypertension defined as a sitting systolic blood pressure \>160 mm Hg or diastolic blood pressure \> 95 mm Hg at screening
8. A positive result for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV)
9. History of alcohol or illicit drug abuse in the past 2 years
10. Known human immunodeficiency virus (HIV) positive based on medical history
11. Life expectancy \< 2 years
12. New York Heart Association (NYHA) Class IV heart failure within 3 months of screening
13. MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening
14. Treatment with an investigational drug within 30 days or within 7 half-lives of the investigational drug, whichever was longer
15. Previous treatment with bexagliflozin or EGT0001474
16. Use of any SGLT2 inhibitors, either at the time of screening or in the prior 3 months
17. Currently participating in another interventional trial
18. Not able to comply with the study scheduled visits
19. 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
20. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome at screening
21. Two or more consecutive FPG measures ≥ 250 mg/dL (13.9 mmol/L) prior to randomization or severe clinical signs or symptoms of hyperglycemia during the washout or run-in periods, including weight loss, blurred vision, increased thirst, or increased urination, or fatigue
22. At last visit prior to randomization, FPG level ≥ 250 mg/dL
23. Prior renal transplantation or evidence of nephrotic syndrome (defined as a urine albumin-to-creatinine ratio (UACR) \> 2000 mg/g at screening).

Primary outcomes:
measure: Change in HbA1c From Baseline at Week 24
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in Systolic Blood Pressure (SBP) From Baseline at Week 24
timeFrame: 24 weeks
measure: Change in Body Weight From Baseline at Week 24 in Subjects With a BMI ≥ 25 Kg/m2
timeFrame: 24 weeks
Other outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) Over Time
timeFrame: 24 weeks
measure: Change From Baseline of HbA1c From Baseline Over Time
timeFrame: 24 weeks
measure: Proportion of Subjects Who Achieve an HbA1c < 7%
timeFrame: Up to 24 weeks
Locations:
city: Canoga Park
country: United States
facility: Research Site
state: California
city: Chino
country: United States
facility: Research Site
state: California
city: Huntington Park
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: Trenton
country: United States
facility: Research Site
state: New Jersey
city: Calabash
country: United States
facility: Research Site
state: North Carolina
city: Morehead City
country: United States
facility: Research Site
state: North Carolina
city: Munroe Falls
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: North Myrtle Beach
country: United States
facility: Research Site
state: South Carolina
city: DeSoto
country: United States
facility: Research Site
state: Texas
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site 2
state: Ontario
city: Toronto
country: Canada
facility: Research Site 1
state: Ontario
city: Pointe-Claire
country: Canada
facility: Research Site
state: Quebec
Study officials:
affiliation: Theracos
name: J. Paul Lock, MD
role: STUDY_DIRECTOR
References: