Inadequately controlled Diabetes Mellitus Type 2. MedDRA version: 20.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Onglyza
Product Name: Saxagliptin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SAXAGLIPTIN
CAS Number: 36144
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Written Informed Consent a) Subjects (or designee) must be willing and able to give signed and dated written informed consent. 2. Target Population a) Subjects with T2DM with inadequate glycemic control, defined as a central laboratory HbA1c >= 7.5% and 270mg/dL but 270mg/dL. b) Subjects should be taking the same daily dose of metformin >=1500 mg for at least 8 weeks prior to the enrollment visit and must not take any other antihyperglycemic therapy for more than 14 days (consecutive or not) during 12 weeks prior to screening. c) BMI 20.0 to 45.0 kg/m2 (inclusive) at the enrollment visit. d) Subject Re-enrollment: This study permits the re-enrollment of a subject who has been discontinued from the study as a pre-treatment failure (ie, subject has not been randomized / has not been treated). If re-enrolled, the subject must be re-consented. Inclusion criteria at randomization (Visit 3, based on laboratory results from Visit 2): a) FPG =18 years old at the time of the screening visit. b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. c) Women must not be breastfeeding d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, and dapagliflozin, and glimepiride plus 5 half-lives of study drugs: saxagliptin, dapagliflozin, and glimepiride (30 days) plu 30 days (duration of ovulatory cycle) for a total of 60 days post-treatment completion. e) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, dapagliflozin, and glimepiride plus 5 half-lives of the study drug (30 days) plus 90 days (duration of sperm turnover) for a total of 120 days post-treatment completion. f) Azoospermic males and WOCBP who are continuously n
Exclusion criteria
Exclusion criteria: Target Disease Exceptions a) Clinical diagnosis of type I DM, known diagnosis of mature onset MODY, secondary DM, or diabetes insipidus. b) History of diabetic ketoacidosis 2. Medical History and Concurrent Diseases a) Any of the following cardiovascular/vascular diseases within 3 months of the enrollment: i) MI ii) Cardiac surgery or revascularization (CABG/PTCA) iii) Unstable angina iv) Unstable CHF v) TIA or significant cerebrovascular disease vi) Unstable or previously undiagnosed arrhythmia vii) CHF, defined as NYHA Class III and IV, unstable or acute CHF and/or known left ventricular EF of =1.5 mg/dL in males or >= 1.4 mg/dL in females). iii) Hematuria (confirmed by microscopy at screening) with no explanation as judged by the investigator up to randomization. If bladder cancer is identified, subjects are not eligible. c) Hepatic diseases (HD) : i) Severe hepatic insufficiency and/or significant abnormal liver function AST> 3x ULN and/or ALT > 3x ULN. ii) Serum total bilirubin > 2.0 mg/dL. iii) Severe HD, including chronic active hepatitis. Positive serologic evidence of current infectious liver disease, including subjects who are positive for HBV viral antibody IgM, HBV surface antigen, and HCV antibody. d) Pancreatic disease i) History of, or current, acute or chronic pancreatitis. e) Hematological and oncological disease/conditions: i) History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis. ii) Malignancy within 5 years of the screening (with the exception of treated BCC or treated SCC). iii) History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time. 3. Physical and Laboratory Test Findings a) Hb <=11.0 g/dL (110 g/L) for men; Hb <=10.0 g/dL (100 g/L) for women. b) An abnormal TSH value at enrollment will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded. (Please refer to the study protocol for re-test conditions) c) Any clinically significant abnormality identified on PE, ECG or laboratory tests, which in the judgment of the investigator would compromise the subjects’ safety or successful participation in the study. 4. Allergies and ADR a) Subjects who have contraindications to therapy as outlined in the saxagliptin and dapagliflozin IBs, the local saxagliptin or dapagliflozin or glimepiride or metformin package insert, including current treatment with potent P450 3A4/5 inhibitors (in countries where dose adjustment would be required by the local saxagliptin label). 5. Other Exclusion Criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the mean change from baseline in HbA1c achieved with saxagliptin, in co-administration with dapagliflozin, added to current background therapy with metformin, compared to glimepiride added to current background therapy with metformin at Week 52.; Secondary Objective: - Compare mean the change from baseline in total body weight achieved with saxagliptin, in co-administration with dapagliflozin, added to current background therapy (CBT) with metformin, compared to glimepiride added to CBT with metformin at W52. - Compare the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c < 7.0%, at W52 with saxagliptin, in co-administration with dapagliflozin, added to CBT with metformin, compared to glimepiride added to CBT with metformin. - Compare the mean change from baseline in systolic blood pressure (SBP) achieved with saxagliptin, in co-administration with dapagliflozin, added to CBT with metformin, compared to glimepiride added to CBT with metformin at W52. - Compare the time to treatment intensification achieved with saxagliptin, in co-admin with dapagliflozin, added to CBT with metformin, compared to glimepiride added to current CBT during the 52 week double-blind treatment period. Objectives continued in protocol. ; Primary end point(s): The primary endpoint for analysis is change from baseline to week 52 in HbA1c. A repeated measures analysis (using a MIXED model) will be used to analyze the change from baseline in HbA1c at Week 52 using values prior to rescue/intensification of treatment. The model will contain terms for treatment group, baseline measurement, time (each relevant visit), the interaction of treatment and time, and the interaction of baseline value and time. Descriptive statistics as well as adjusted means and 95% confidence intervals will be calculated for the change fro | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 52 for secondary endpoints for analysis for the short-term treatment period. Week 156 for secondary endpoints for analysis for the long-term treatment period; Secondary end point(s): Secondary endpoints for analysis for the short-term treatment period include: - Mean change from baseline in total body weight at Week 52 - Proportion of subjects achieving a therapeutic glycemic response (HbA1c < 7.0 %) at Week 52. - Mean change from baseline in systolic blood pressure (SBP) at Week 52. - Time to treatment intensification (addition of insulin or other glucose-lowering agents for rescue therapy or discontinuation for lack of glycemic control) during the 52-week double-blind controlled treatment period. Secondary endpoints for analysis for the long-term treatment period include: - Time to treatment intensification (addition of insulin or other glucose-lowering agents for rescue therapy or discontinuation for lack of glycemic control) during the 156-week treatment period. - Proportion of subjects achieving therapeutic glycemic response (HbA1c < 7.0%) at Week 156. | — |
Countries
Czech Republic, Germany, Hungary, Mexico, Poland, Romania, Russian Federation, Sweden, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed