E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063624 |
E.1.2 | Term | Type II diabetes mellitus inadequate control |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary efficacy objective of this trial is to demonstrate that bexagliflozin is non-inferior to sitagliptin by evaluating the treatment effect on HbA1c reduction at week 24 in subjects whose T2DM is inadequately controlled by metformin. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in fasting plasma glucose (FPG) at week 24
•To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in body weight in subjects with baseline body mass index (BMI) ≥ 25 kg/m2 at week 24
•To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in systolic blood pressure (SBP) in subjects at week 24
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female adult subjects ≥ 18 years of age
2.If subjects are female of childbearing potential, subjects must be negative on the urine pregnancy test and agree to abstain from coitus or use contraception during the entire study
3.Subjects with a diagnosis of T2DM with HbA1c levels between 7.0% and 11% (inclusive) at screening
4.Subjects whose T2DM is treated with a stable dose of ≥ 1500 mg/day metformin only along with diet and exercise counseling for at least 8 weeks prior to screening
5.Subjects have a BMI ≤ 45 kg/m2 at screening
6.If applicable, taking stable doses of treatment for dyslipidemia and/or hypertension for 30 days prior to screening
7.Subjects who are willing and able to return for all clinic visits and to complete all study-required procedures, including SMBG measurements
Prior to randomization, all subjects must:
8.Adhere to the investigational product administration requirements as evidenced by missing no more than 1 day of run-in medications. If run-in medication doses are missed for reasons that, in the judgement of the investigator, are appropriate, this requirement may be waived |
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E.4 | Principal exclusion criteria |
1.Diagnosis of type 1 diabetes mellitus or maturity–onset diabetes of the young (MODY)
2.Hemoglobinopathy that affects HbA1c measurement
3.Any contraindication to the safe use of DPP4 therapy or sitagliptin, including known hypersensitivity reaction
4.History of pancreatitis
5.Genitourinary tract infection within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within 6 months from screening
6.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)
7.History of alcohol or illicit drug abuse in the past 2 years
8.Triglycerides > 500 mg/dl at Visit V1
9.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
10.eGFR, as calculated by the modification of diet in renal disease study equation (MDRD), < 60 mL/min/1.73 m2 at screening.
11.Uncontrolled hypertension (SBP > 160 mmHg or diastolic BP > 95 mmHg) at Visit V1
12.Life expectancy < 2 years
13.History of MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening
14.History of treatment with an investigational drug within 30 days or within 7 half-lives of the investigational drug, whichever is longer
15.Previous treatment with bexagliflozin or EGT0001474 study drug (run-in or double-blind investigational product)
16.Currently or within 3 months of taking any SGLT2 inhibitor
17.Currently participating in another interventional trial
18.Prior renal transplantation or evidence of nephrotic syndrome (defined as a urine albumin-to-creatinine ratio (UACR) > 1500 mg/g at screening).
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.Female subjects who are pregnant or nursing
21.Two or more consecutive SMBG measures ≥ 250 mg/dL (13.9 mmol/L) prior to randomization accompanied by clinical signs or symptoms of hyperglycemia prior to randomization, including weight loss, blurred vision, increased thirst, increased urination, or fatigue
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from baseline at week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Fasting plasma glucose measurement at baseline and week 24. |
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E.5.2 | Secondary end point(s) |
•Change in FPG from baseline at week 24
•Change in body weight in subjects with baseline BMI ≥ 25 kg/m2 at week 24
•Change in SBP in subjects from baseline at week 24
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
FPG measurement at week 24
Body weight in subjects with baseline BMI ≥ 25 kg/m2 measurement at week 24
SBP measurement at week 24
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
Hungary |
Poland |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |