None listed
Conditions
Interventions
GROUP 1 Type of group
Selection Phase: Duration of 12 weeks. All subjects will be treated with a TZD. Pioglitazone 30 or 45 mg PO QD or Rosiglitazone 4 or 8 mg PO QD.
Preparatory Phase: Duration of 2 weeks. All subjects will keep the drug and the established dose of TZD from the selection phase. In addition they will receive Saxagliptin Placebo PO QD.
Treatment Phase. Duration of 24 weeks. This group will continue with the established TZD + Saxagliptin 2.5 mg PO QD.
Long-term Extension Phase: Duration of 12
Selection Phase: Duration of 12 weeks. All subjects will be treated with a TZD. Pioglitazone 30 or 45 mg PO QD or Rosiglitazone 4 or 8 mg PO QD.
Preparatory Phase: Duration of 2 weeks. All subjects will keep the drug and the established dose of TZD from the selection phase. In addition they will receive Saxagliptin Placebo PO QD.
Treatment Phase. Duration of 24 weeks. This group will continue with the established TZD + Saxagliptin Placebo PO QD.
Long-term Extension Phase: Duration of 12
Sponsors
BRISTOL MYERS SQUIBB COMPANY,
Eligibility
Inclusion criteria
Inclusion criteria: 804/5000 1) Subjects must be willing to give written informed consent and be able to do so. 2) Subjects with type 2 diabetes who have received treatment with a stable monotherapy dose of a TZD (pioglitazone 30mg or 45mg, once a day, or rosiglitazone 4mg, once a day, or 8mg, either once a day or in two doses of 4mg) for at least 12 weeks before selection. 3) A1C ≥ 7.0% and ≤ 10%. 4) Fasting peptide-C concentration ≥ 1.0 ng / ml. 5) Body mass index ≤ 40 kg / m2. 6) Men and women, ≥18 and ≤77 years of age. Women should not be breastfeeding or pregnant. Women of childbearing age (WOCBP) should use adequate contraception to avoid pregnancy during the study and up to 4 weeks after the study.
Exclusion criteria
Exclusion criteria: 1) WOCBP who do not wish or can not use an acceptable method to avoid pregnancy during the entire course of the study and up to 4 weeks after the study. 2) WOCBP using a prohibited method of contraception. 3) Pregnant or lactating women. 4) Women with a positive pregnancy analysis at the time of admission or prior to the administration of the study medication. 5) Symptoms of poorly controlled diabetes. 6) History of diabetic ketoacidosis or hyperosmolar non-ketotic coma. 7) Insulin therapy within the year prior to selection. 8) Important cardiovascular antecedents. 9) Repeated or chronic intermittent corticosteroid treatment. 10) History of instable or rapidly evolving renal disease. 11) History of drug or alcohol 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 in research or participation in a clinical research trial within 30 days prior to randomization. 17) Any table that may incapacitate the subject to complete the study or may pose a significant risk to it. 18) Liver disease and / or significant abnormal liver function. 19 History of positive serological evidence of current infectious liver disease. 20) Serum creatinine (Scr)> 2.0 mg / dL (176 μmol / L). 21) Creatine kinase ≥ 3x ULN. 22) Anemia of any etiology defined as hemoglobin ≤ 12.0 g / dL (120 g / L) in men and hemoglobin ≤ 11.0 g / dL (110 g / L) in women. 23) Absolute lymphocyte count less than 1000 cells / mm3. 24) Platelet count <140,000 cells / uL. 25) Subjects with an abnormal TSH value in the selection will be subjected to an additional evaluation of free T4. Subjects with abnormal free T4 will be excluded. 26) Subjects that present contraindications for therapy. 27) Background of administration of any antihyperglycemic therapy for twelve weeks before selection. 28) Treatment with potent systemic inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4). 29) Previous treatment with saxagliptin or any DPP-IV inhibitor. 30) Prisoners or subjects who are required to be detained for treatment because of a psychiatric or physical illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Levels in peripheral blood of glycosylated hemoglobin (A1C). Measure:Change from the baseline visit at the A1C level. Timepoints:Week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Oral Glucose Tolerance Test (OGTT): +30, +60, +120 and +180 minutes after the beginning of the ingestion of 75 grams of oral glucose solution. FPG and A1C in peripheral blood samples. Measure:Secondary efficacy: 1) The change from the baseline visit in the area under the curve (AUC) from 0 to 180 minutes for the postprandial glucose response (PPG) to an Oral Glucose Tolerance Test (OGTT). 2) The change from baseline in fasting plasma glucose (FPG). 3) The proportion of subjects that reach a therapeutic glycemic response defined as A1C <7.0%. Timepoints:Week 24. ; Outcome name:Laboratory tests: OGTT, A1C, Glucagon, insulin, peptide C. Measure:1) The proportion of subjects that reach a glycemic response defined as A1C <6.5%. 2) Area under the curve (AUC) from 0 to 180 minutes for the response of glucagon, insulin and postprandial C-peptide to an OGTT. 3) Fasting glucagon, insulin and C-peptide. 4) Change from baseline in the levels of glucose, glucagon, C-peptide and insulin at 0, 30, 60, 120 and 180 minutes after an OGTT. 5) Change from the baseline visit in insulin sensitivity and B cell function derived from measurements of insulin, C-peptide and glucose during an oral glucose tolerance test. Timepoints:A1C, glucagon, insulin, peptide C: Before starting the study and in weeks 2, 4, 6, 8, 12, 16, 20, 24, 30, 37, 50, 63 and 76. OGTT: Before the study and in weeks 24 and 76. ; Outcome name:1) Function of the beta cells, according to the measurement of an evaluation of the Homeostasis Model (HOMA). 2) Insulin resistance, as measured by HOMA-IR. For the calculation of HOMA and HOMA-IR the insulin and glucose values in fasting will be required. Measure:1) Function of beta cells. 2) Insulin resistance. Timepoints:Insulin and fasting glucose: Before starting the study and in weeks 2, 4, 6, 8, 12, 16, 20, 24, 30, 37, 50, 63 and 76. ; Outcome name:BMI: Weight and size of the subjects. Glycemic | — |
Countries
Argentina, Canada, India, Mexico, Peru, Philippines, United States
Outcome results
None listed