Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes mellitus, SGLT inhibitors, dose-response
Brief summary
The purpose of the study is to evaluate the efficacy, tolerability and short-term safety of LIK066 to support dose selection for phase 3.
Interventions
DRUGLIK066
Experimental treatment doses
DRUGSitagliptin
Active comparator treatment dose
DRUGPlacebo
Placebo comparator dose
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of T2DM by standard criteria 2. Drug-naïve patients, defined as patients not having received any anti-diabetic medication previously, 3. Currently untreated patients , who, after the diagnosis of T2DM, have received anti-diabetic medication for not more than 12 consecutive weeks, and have not received any anti-diabetic treatment within 12 weeks prior to Visit 1 4. Patients being treated with mono-therapy for at least 8 consecutive weeks prior to Visit 1 with the following OADs: metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), SU, glinide, alpha-glucosidase inhibitor (AGI) 5. HbA1c ≥ 7 to ≤ 10.5% at Visit 1 for drug-naïve/currently untreated patients 6. HbA1c ≥ 7 to ≤ 9.5% at Visit 1 for patients treated with OAD monotherapy 7. HbA1c ≥ 7 to ≤ 10.5% at Visit 199 for ALL patients 8. Age: ≥18 and ≤ 75 years old at Visit 1 9. BMI ≥22 to ≤45 kg/m2 at Visit 1
Exclusion criteria
1. FPG ≥270 mg/dl (15 mmol/L) for drug-naïve/currently untreated patients or ≥240 mg/dl (13.3 mmol/L) for patients on OAD monotherapy at Visit 1 2. Insulin treatment \>4 consecutive weeks in the last 6 months, corticosteroid use \>7 days in the last 8 weeks, use of growth hormones in the last 6 months, or use of weight control products \> 4 weeks in the last 6 months 3. History of acute metabolic complications, CV disease, type 1 diabetes mellitus, hepatic disorders, pancreatitis, chronic diarrhea 4. Significant lab abnormalities such as TSH outside of normal range, UACR\>300 mg/g creatinine, eGFR \<60 ml/min/1.73m2, hemoglobin \<12 g/L in men and \<11 g/L in women, hematuria 5. ECG abnormalities including AV block, long QT syndrome or QTc\>450 msec for men and \>470 msec for women 6. History of malignancy 7. Women of child-bearing potential not using effective methods of contraception Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in glycated hemoglobin (HbA1c) after 12 weeks | baseline, 12 weeks | Change from baseline in HbA1c after 12 weeks of treatment in each of the LIK066 doses and placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in beta cell function during a meal test | baseline, 12 weeks | The effect of LIK066 on change in beta cell function during a meal test after 12 weeks of treatment will be evaluated. |
| Change from baseline in insulin secretion relative to glucose during a meal test | baseline, 12 weeks | The effect of LIK066on change in insulin secretion relative to glucose during a meal test after 12 weeks of treatment will be evaluated. |
| Change from baseline in Fasting Plasma Glucose | baseline, 12 weeks | The effect of LIK066 on fasting plasma glucose after 12 weeks of treatment will be evaluated. |
| Change from baseline in urinary glucose to creatinine ratio | baseline, 12 weeks | The effect of LIK066 on urinary glucose to creatinine ratio after 12 weeks of treatment will be evaluated |
| Change from baseline in Body weight | baseline, 12 weeks | The effect of LIK066 on change in body weight after 12 weeks of treatment will be evaluated. |
| Change from baseline in postprandial glucose during a meal test | baseline, 12 weeks | The effect of LIK066 on change in postprandial glucose during a meal test after 12 weeks of treatment will be evaluated. |
| Change from baseline in oral glucose insulin sensitivity during a meal test | baseline, 12 weeks | The effect of LIK066 on change in oral glucose insulin sensitivity during a meal test after 12 weeks of treatment will be evaluated. |
| Change from baseline in glucagon-like peptide response during a meal test | baseline, 12 weeks | The effect of LIK066 on change in glucagon-like peptide during a meal test after 12 weeks of treatment will be evaluated. |
| Change from baseline in Peptide YY response during a meal test | baseline, 12 weeks | The effect of LIK066 on change in peptide YY response during a meal test after 12 weeks of treatment will be evaluated. |
| Number of patients with adverse events to assess safety and tolerability of LIK066 | 12 weeks | The safety and tolerability of 7 doses of LIK066 after 12 weeks of treatment will be evaluated with number of patients reported for total adverse events, serious adverse events and death. |
| Change from baseline in renal threshold for glucose excretion | baseline, 12 weeks | The effect of LIK066 on renal threshold for glucose excretion will be calculated from glucose values in an overnight urine collection |
| Change from baseline in Blood pressure | baseline, 12 weeks | The effect of LIK066 on change in systolic and diastolic blood pressure after 12 weeks of treatment will be evaluated. |
Outcome results
None listed