Dose-finding Study of LIK066 Compared With Placebo or Sitagliptin to Evaluate Change in HbA1c in Patients With Diabetes

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy, tolerability and short-term safety of LIK066 to support dose selection for phase 3.

Official Title
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A Multi-center, Randomized, Double-blind, Parallel-group Dose-finding Study to Evaluate Change in HbA1c After 12 Weeks Monotherapy With 7 Doses of LIK066 Compared With Placebo or Sitagliptin in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: LIK066
* Drug: Sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LIK066 2.5 mg<br>Patients receive 2.5 mg of LIK066 once daily for 12 weeks | Drug: LIK066<br>* Experimental treatment doses<br>|
| Experimental: LIK066 5 mg<br>Patients receive 5 mg of LIK066 once daily for 12 weeks | Drug: LIK066<br>* Experimental treatment doses<br>|
| Experimental: LIK066 10 mg<br>Patients receive 10 mg of LIK066 once daily for 12 weeks | Drug: LIK066<br>* Experimental treatment doses<br>|
| Experimental: LIK066 25 mg<br>Patients receive 25 mg of LIK066 once daily for 12 weeks | Drug: LIK066<br>* Experimental treatment doses<br>|
| Experimental: LIK066 50 mg<br>Patients receive 50 mg of LIK066 once daily for 12 weeks | Drug: LIK066<br>* Experimental treatment doses<br>|
| Experimental: LIK066 100 mg<br>Patients receive 100 mg of LIK066 once daily for 12 weeks | Drug: LIK066<br>* Experimental treatment doses<br>|
| Experimental: LIK066 150 mg<br>Patients receive 150 mg of LIK066 once daily for 12 weeks | Drug: LIK066<br>* Experimental treatment doses<br>|
| Active Comparator: Sitagliptin 100 mg<br>Patients receive 100 mg sitagliptin once daily for 12 weeks | Drug: Sitagliptin<br>* Active comparator treatment dose<br>|
| Placebo Comparator: Placebo<br>Patients receive placebo for 12 weeks | Drug: Placebo<br>* Placebo comparator dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in glycated hemoglobin (HbA1c) after 12 weeks | Change from baseline in HbA1c after 12 weeks of treatment in each of the LIK066 doses and placebo | baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Fasting Plasma Glucose | The effect of LIK066 on fasting plasma glucose after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in urinary glucose to creatinine ratio | The effect of LIK066 on urinary glucose to creatinine ratio after 12 weeks of treatment will be evaluated | baseline, 12 weeks | 
| Change from baseline in Body weight | The effect of LIK066 on change in body weight after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in Blood pressure | The effect of LIK066 on change in systolic and diastolic blood pressure after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in postprandial glucose during a meal test | The effect of LIK066 on change in postprandial glucose during a meal test after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in beta cell function during a meal test | The effect of LIK066 on change in beta cell function during a meal test after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in insulin secretion relative to glucose during a meal test | The effect of LIK066on change in insulin secretion relative to glucose during a meal test after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in oral glucose insulin sensitivity during a meal test | The effect of LIK066 on change in oral glucose insulin sensitivity during a meal test after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in glucagon-like peptide response during a meal test | The effect of LIK066 on change in glucagon-like peptide during a meal test after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Change from baseline in Peptide YY response during a meal test | The effect of LIK066 on change in peptide YY response during a meal test after 12 weeks of treatment will be evaluated. | baseline, 12 weeks | 
| Number of patients with adverse events to assess safety and tolerability of LIK066 | 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. | 12 weeks | 
| Change from baseline in renal threshold for glucose excretion | The effect of LIK066 on renal threshold for glucose excretion will be calculated from glucose values in an overnight urine collection | baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes mellitus, SGLT inhibitors, dose-response