A double blind placebo controlled study to evaluate the effect of bexagliflozin tablets on hemoglobin A1c in patients with type 2 diabetes mellitus and moderate renal impairment

• Register: EUCTR
• Last refreshed on: 5 February 2018
• Main ID: EUCTR2016-002580-34-ES
• Date of registration: 11/08/2016
• Prospective Registration: Yes
• Primary sponsor: Theracos Sub, LLC
• Public title: A double blind placebo controlled study to evaluate the effect of bexagliflozin tablets on hemoglobin A1c in patients with type 2 diabetes mellitus and moderate renal impairment
• Scientific title: A double blind placebo controlled study to evaluate the effect of bexagliflozin tablets on hemoglobin A1c in patients with type 2 diabetes mellitus and moderate renal impairment
• Date of first enrolment: 06/09/2016
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002580-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Croatia, France, Japan, Spain, United States

Contacts

• Name: Clinical Trial Project Management
• Affiliation: Translational Medicine Group

• Name: Clinical Trial Project Management
• Affiliation: Translational Medicine Group

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men or non-pregnant women = 20 years of age. Women of childbearing potential must agree to use contraception during the entire study to avoid any possible pregnancy.
Females who are surgically sterile (hysterectomy, oophorectomy) or postmenopausal (absence of menses greater than 12 months and age > 45 years) are eligible if they test negative on the urine pregnancy test.
2. Subjects with a diagnosis of T2DM with an HbA1c between 7.0 and 10.5% (inclusive) at the time of screening.
3. Subjects who are treatment naïve or are treated with a stable regimen of anti-diabetic medications. At the time of screening, the doses and frequency of all anti-diabetic medications must have been stable for 8 weeks.
4. Subjects who have an estimated glomerular filtration rate (eGFR) = 30 and
< 60 mL/min/1.73 m2 at 2 time points: screening (V1), and 1 additional time point between 1 and 12 monhs of screening (may be obtained from available medical records).
The eGFR will be calculated by the MDRD equation.
5. Subjects who have a body mass index (BMI) = 45 kg/m2 (inclusive)
6. Subjects who taking stable doses of medications for hypertension or hyperlipidemia for at least 30 days prior to randomization
7. Subjects who have stable eGFR between the historic value and day of screening (no more than 20% change in eGFR).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
1. Diagnosis of type 1 diabetes mellitus or maturity–onset diabetes of the young (MODY)
2. Hemoglobinopathy that affects HbA1c measurement
3. Frequent symptomatic hypoglycemia (greater than one episode per week on average)
4. Genitourinary tract infection within 6 weeks of screening or history of = 3 genitourinary infections requiring treatment within the last 6 months
5. Cancer, active or in remission for < 3 years (Non-melanoma skin cancer or basal cell carcinoma or carcinoma in situ of the cervix will not be grounds for exclusion)
6. History of alcohol or illicit drug abuse in the past 2 years
7. Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase > 1.5 x upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN
8. History of MI, stroke or hospitalization for heart failure, or hospitalization for unstable angina in the prior 3 months
9. Evidence of NYHA class IV heart failure at screening or randomization
10. Currently or within 3 months of taking an SGLT2 inhibitor from screening (Appendix 5)
11. Any condition, disease, disorder, or clinically relevant laboratory abnormality that, in the opinion of the PI, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment
12. Women who are pregnant or breastfeeding
13. Patients who are receiving renal replacement therapy (peritoneal or hemodialysis) or who have undergone renal transplantation
14. Corrected serum calcium < 8 mg/dL (Appendix 4) at screening (V1) or randomization (V3)
15. Uncontrolled hypertension (systolic blood pressure > 170 or diastolic blood pressure> 110)
16. Currently participating in another interventional trial or receiving treatment with an investigational drug within 30 days or 7 half-lives of screening, whichever is longer
17. Previous treatment with bexagliflozin or EGT0001474
18. Missing 1 or more doses of the study drug during the run-in period
19. Fasting blood glucose value during the run-in period = 250 mg/dL (13.9 mmol/L) associated with severe clinical signs or symptoms of hyperglycemia
20. Any episode of symptomatic hypoglycemia during the run-in period in which symptoms are severe
21. Subjects who are unable to read and write in their native language
22. Subjects who are unable to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetes Mellitus Type 2 with renal imparement
MedDRA version: 19.0 Level: LLT Classification code 10045250 Term: Type II diabetes mellitus with renal manifestations System Organ Class: 100000004857

Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Intervention(s)

Product Name: Bexagliflozina
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: BEXAGLIFLOZINA
CAS Number: 1118567-05-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To assess the effect of bexagliflozin on the change in body weight at week 24 in subjects
with baseline BMI = 25 kg/m2
• To assess the effect of bexagliflozin on the change in systolic blood pressure (SBP) at week 24 in subjects with baseline SBP = 130 mmHg
• Change in HbA1c in subjects with eGFR 45 to 59 mL/min/1.73 m2 at week 24
• Change in HbA1c in subjects with eGFR 30 to 44 mL/min/1.73 m2 at week 24

Timepoint(s) of evaluation of this end point: Change of HbA1c from baseline over 24 weeks of treatment

Main Objective: The primary objective of this study is to determine the efficacy of bexagliflozin on lowering HbA1c in patients with type 2 diabetes mellitus and moderate renal impairment.

Primary end point(s): Change of HbA1c from baseline to week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: To assess the treatment effect on the change of body weight in subjects with baseline BMI =25 kg/m2 at week 24, an analysis of covariance model (ANCOVA) will be implemented using all available data at week 24.
The change in systolic blood pressure (SBP) in subjects with baseline SBP = 130 mmHg in the bexagliflozin group compared with placebo at week 24 will be analyzed using the similar
method with baseline SBP measure as a covariate. The same analysis method applies for the testing of changes in HbA1c at week 24 for subjects with baseline eGFR 45- 59 mL/min/1.73m2, and for subjects with baseline eGFR 30-44 mL/min/1.73m2

Secondary end point(s): • Change in body weight in subjects with baseline body mass index (BMI) =25 kg/m
• Changes in systolic blood pressure (SBP) over time in subjects with baseline SBP =130 mmHg
• Change in HbA1c over time in subjects with eGFR 45 to 59 mL/min/1.73 m2
• Change in HbA1c over time in subjects with eGFR 30 to 44 mL/min/1.73 m2

Secondary ID(s)

UPI number 498543

THR-1442-C-448

NCT02836873

Source(s) of Monetary Support

Theracos Sub, LLC