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

Phase 1

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: LIK066
Drug: Placebo

Registration Number: NCT01915849

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg	Placebo	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.
Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg	LIK066	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.
Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg	Placebo	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.
Sequence 3: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg	Placebo	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.
Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo	Placebo	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.
Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg	LIK066	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.
Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo	LIK066	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.
Sequence 3: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg	LIK066	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.

Primary Outcome Measures

Name	Time	Method
Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose	Day 1 and Day 4 (pre-meal, every half hour till 5 hour on Day 1 and Day 4)	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.

Secondary Outcome Measures