Dose-finding Study of LIK066 Compared With Placebo or Sitagliptin to Evaluate Change in HbA1c in Patients With Diabetes
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT01824264
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Confirmed diagnosis of T2DM by standard criteria
- Drug-naïve patients, defined as patients not having received any anti-diabetic medication previously,
- 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
- 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)
- HbA1c ≥ 7 to ≤ 10.5% at Visit 1 for drug-naïve/currently untreated patients
- HbA1c ≥ 7 to ≤ 9.5% at Visit 1 for patients treated with OAD monotherapy
- HbA1c ≥ 7 to ≤ 10.5% at Visit 199 for ALL patients
- Age: ≥18 and ≤ 75 years old at Visit 1
- BMI ≥22 to ≤45 kg/m2 at Visit 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
- 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
- History of acute metabolic complications, CV disease, type 1 diabetes mellitus, hepatic disorders, pancreatitis, chronic diarrhea
- 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
- ECG abnormalities including AV block, long QT syndrome or QTc>450 msec for men and >470 msec for women
- History of malignancy
- Women of child-bearing potential not using effective methods of contraception Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LIK066 10 mg LIK066 Patients receive 10 mg of LIK066 once daily for 12 weeks LIK066 25 mg LIK066 Patients receive 25 mg of LIK066 once daily for 12 weeks LIK066 50 mg LIK066 Patients receive 50 mg of LIK066 once daily for 12 weeks LIK066 150 mg LIK066 Patients receive 150 mg of LIK066 once daily for 12 weeks LIK066 2.5 mg LIK066 Patients receive 2.5 mg of LIK066 once daily for 12 weeks LIK066 5 mg LIK066 Patients receive 5 mg of LIK066 once daily for 12 weeks Sitagliptin 100 mg Sitagliptin Patients receive 100 mg sitagliptin once daily for 12 weeks Placebo Placebo Patients receive placebo for 12 weeks LIK066 100 mg LIK066 Patients receive 100 mg of LIK066 once daily for 12 weeks
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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.
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 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 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