None listed
Conditions
Interventions
GROUP 1 Type of group
1) INTRODUCTION PHASE: Duration of 4 weeks. All patients will receive Glibenclamide in 7.5 mg, in capsules, PO QD, the dose will be adjusted according to clinical criteria.
2) SHORT-TERM TREATMENT PHASE: Duration of 24 weeks. This group will be treated with Saxagliptin 2.5 mg tablets PO QD + Glibenclamide 7.5 mg, in capsules, PO QD + Metformin 500 to 2500 mg PO QD or BID (as rescue medicine).
3) LONG-TERM EXTENSION PHASE: Duration of 12 months. The doses will continue unchanged, and the do
1) INTRODUCTION PHASE: Duration of 4 weeks. All patients will receive Glibenclamide in 7.5 mg, in capsules, PO QD, the dose will be adjusted according to clinical criteria.
2) SHORT-TERM TREATMENT PHASE: Duration of 24 weeks. This group will be treated with Saxagliptin Placebo in tablets PO QD + Glibenclamide 10 mg, divided into 2 doses: 2.5 mg and of 7.5 mg, in capsules, PO, being able to adjust up to 15 mg PO QD + Metformin 500 to 2500 mg PO QD or IDB (as a rescue medicine).
3) LONG-TERM
Sponsors
BRISTOL MYERS SQUIBB COMPANY,
Eligibility
Inclusion criteria
Inclusion criteria: 1) Patients must want and be able to sign written informed consent. 2) Patients with type 2 diabetes mellitus that required treatment with a submaximal dose of a sulphonylurea for ≥ 2 months and ≤ 12 months. 3) HbA1C ≥ 7.5% and ≤ 10.0% obtained at the screening visit. 4) HbA1C ≥ 7.0% and MFPG ≥140 mg / dl (7.8 mmo / l) or MFWBG ≥131 mg / dl (7.3 mmol / l) or GPA (central laboratory) ≥ 140 mg / dl ( 7.8 mmol / l) in the randomization. 5) Fasting C-peptide concentration ≥ 1.0 ng / ml. 6) Body mass index ≤ 40 kg / m2. 7) Men and women, ≥18 and ≤77 years of age. Women should not be breastfeeding and should not be pregnant. Women of childbearing age (WOCBP) should use an adequate method of contraception to avoid pregnancy during the study and up to 4 weeks after the study.
Exclusion criteria
Exclusion criteria: 1) WOCBP who are unable or unwilling to use an acceptable method to avoid pregnancy during the entire study period and for up to 4 weeks after the study. 2) WOCBP using a prohibited method of contraception. 3) Women who are pregnant or breastfeeding. 4) Women with a positive pregnancy test at admission or in the introduction phase or before the administration of the study medication. 5) Diabetes that is poorly controlled. 6) History of diabetic ketoacidosis or hyperosmolar non-ketotic coma. 7) Treatment with insulin within one year of the selection. 8) Significant cardiovascular history. 9) Chronic corticosteroid treatment or repeated intermittently. 10) History of unstable or rapidly progressive renal disease. 11) History of alcohol or drug abuse within the previous year. 12) Unstable major psychiatric disorders. 13) Immunocompromised individuals. 14) History of hemoglobinopathies. 15) Donation of blood or plasma to a blood bank within three months of the selection. 16) Administration of any other medication under investigation or participation in a clinical research study within 30 days of the expected admission to the phase of introduction of this study. 17) Any condition that may cause the patient to be unable to complete the study or that may pose a significant risk to the patient. 18) Active liver disease and / or liver function significantly abnormal. 19) History of positive serological evidence of current infectious liver disease. 20) Serum creatinine (Scr) ≥ 2.0 mg / dl (176 umol / l). 21) Creatinine kinase ≥ 3 x ULN. 22) Anemia, of any etiology. 23) Absolute lymphocyte count ≤1000 cells / mm3 24) Platelet count <140,000 cells / ul. 25) Patients who present an abnormal TSH value in the selection will undergo a greater evaluation with free T4. Patients with abnormal free T4 will be excluded. 26) Patients who have contraindications to treatment. 27) History of administration of any treatment for hyperglycemia (apart from sulfonylureas) for more than three consecutive days or seven non-consecutive days during the twelve weeks prior to selection. 28) Use of any other medication against hyperglycemia after entry into the introduction phase. 29) Treatments with potent inhibitors or inducers of cytochrome P450 3A4. 30) Previous treatment with saxagliptin or any DPP-IV inhibitor. 31) Prisoners or patients who are detained for the treatment of a psychiatric or physical illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Serum levels of HbA1C. Measure:Average change in HbA1C from baseline to week 24. Timepoints:Before starting treatment, day 1 and weeks 4, 6, 8, 12, 16, 20 and 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Oral glucose tolerance test (PTOG). Fasting plasma glucose (GPA). Serum levels of HbA1C. Measure:Change from baseline in the area under the curve (ABC) from 0 to 180 minutes in the postprandial glucose response (GPP). change from baseline in fasting plasma glycemia (GPA). Proportion of patients achieving a therapeutic response to blood glucose that is defined as AI <7.0%. Timepoints:Oral glucose tolerance test (PTOG): Before starting treatment and in weeks 24 and 76. Fasting plasma glucose (GPA): Before starting treatment, day 1 and in weeks 2, 4, 6, 8, 12, 16, 20, 24, 30, 37, 50, 63 and 76. Serum levels of HbA1C: Before starting treatment, day 1 and in weeks 4, 6, 8, 12, 16, 20, 24, 30, 37, 50, 63 and 76. ; Outcome name:Levels of glucose, glucagon, C-peptide and insulin after an oral glucose tolerance test (PTOG). Serum levels of HbA1C. The function of the beta cells will be measured by the Homeostasis Evaluation Model (HOMA). Insulin resistance will be measured by the HOMA-IR. Measure:1) Proportion of patients achieving an A1C ≤ 6.5%. 2) The area under the curve (AUC) from 0 to 180 minutes for glucagon, insulin and postprandial C-peptide. 3) Function of beta cells. 4) Insulin resistance. 5) Fasting glucagon, insulin and C-peptide. 6) Change from the baseline in the levels of glucose, glucagon, C-peptide and insulin at 0 minutes, 30 minutes, 60 minutes, 120 minutes and 180 minutes after a PTOG. Timepoints:Before starting the treatment and in weeks 24 and 76. ; Outcome name:1) HbA1C serum levels. 2), 5), 6) Glucose, glucagon, C-peptide and fasting insulin levels and then after an oral glucose tolerance test (PTOG). 3) The function of the beta cells will be measured by the Homeostasis Evaluation Model (HOMA). 4) Insulin resistance will be measured by the HOMA-IR. Measure:Other Efficacy Criteria I: 1) The proportion of patients achieving an A1C ≤ 6.5%. 2) The area under | — |
Countries
Argentina, Brazil, China, Israel, Korea South, Mexico, Peru, Philippines, Puerto Rico, Singapore, South Africa, Taiwan, Thailand, United States
Outcome results
None listed