Effect of LIK066 on Glucose Absorption in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of the study was to assess the effect of LIK066 on intestinal glucose absorption immediately after a single dose (immediate effect) and 6 hours following the dose (after multiple daily doses; sustained effect) in patients with type 2 diabetes mellitus (T2DM).

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Crossover Trial to Assess the Effect of Orally Administered LIK066 on Glucose Absorption in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: LIK066
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients, age 18-65 years, must have been diagnosed with T2DM at least 6 months prior to screening with HbA1c 6.5 to 10.0%, inclusive, at screening. Fasting plasma glucose ≤250mg/dL at screening. If treated with metformin, patients must be on a stable dose for 12 weeks prior to randomization and maintain the dose until the end of the study. Exclusion Criteria: Patients with type 1 diabetes mellitus. Patients with history of acute diabetic complications within the 6 months prior to screening. Pregnant or nursing (lactating) women. Women of child-bearing potential unless they are using effective methods of contraception during dosing of study treatment. Patients with signs or symptoms of significant diabetic complications. Patients treated with certain blood pressure or lipid lowering medications unless patients have been on stable doses for the 12 weeks prior to dosing. History of drug or alcohol abuse within the 12 months prior to dosing. Any surgical or medical condition, acute or unstable chronic disease which may, based on the investigator's opinion, jeopardize the patient in case of participation in the study. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg<br>Period 1- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 2- Placebo treatment once daily for 4 days Period 3 - LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 150 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods. | Drug: LIK066<br>* LIK066 15 mg, 50 mg and 150 mg<br>Drug: Placebo<br> <br> |
| Experimental: Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo<br>Period 1- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 4- Placebo treatment once daily for 4 days. 14 days washout periods between treatment periods. | Drug: LIK066<br>* LIK066 15 mg, 50 mg and 150 mg<br>Drug: Placebo<br> <br> |
| Experimental: Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg<br>Period 1- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 2- LIK066 50 mg treatment once daily (q.d.) for 4 days. Period 3- Placebo treatment once daily for 4 days. Period 4- LIK066 15 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods. | Drug: LIK066<br>* LIK066 15 mg, 50 mg and 150 mg<br>Drug: Placebo<br> <br> |
| Experimental: Sequence 3: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg<br>Period 1- Placebo treatment once daily (q.d.) for 4 days. Period 2- LIK066 150 mg treatment once daily (q.d.) for 4 days. Period 3- LIK066 15 mg treatment once daily (q.d.) for 4 days. Period 4- LIK066 50 mg treatment once daily (q.d.) for 4 days. 14 days washout periods between treatment periods. | Drug: LIK066<br>* LIK066 15 mg, 50 mg and 150 mg<br>Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Glucose fluxes during a mixed meal were measured using a dual glucose tracer method and non-steady state Steele equations. The rate of appearance of meal (or exogenous) glucose in the blood (also referred to as intestinal glucose absorption or Ra meal) after a mixed meal following LIK066 administration on Days 1 and 4 was the primary PD assessment in this study.The postprandial AUC was calculated using the linear trapezoidal rule. The sample collected at 7 hours after the start of the infusion was treated as the pre-meal, 0 hour measurement for the AUC0-5 hr calculation. | Day 1 and Day 4 (pre-meal, every half hour till 5 hour on Day 1 and Day 4) |