Type 2 Diabetes Mellitus
Conditions
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).
Interventions
DRUGLIK066
LIK066 15 mg, 50 mg and 150 mg
DRUGPlacebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg 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. | 5 |
| Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/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. | 3 |
| Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg 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. | 3 |
| Sequence 4: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg 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. | 3 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 (4 Days) | Protocol Violation | 1 | 0 | 0 | 0 |
| Treatment Period 1 (4 Days) | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Sequence 1: LIK066 15 mg/Placebo/LIK066 50 mg/LIK066 150 mg | Sequence 2: LIK066 50 mg/LIK066 15 mg/LIK066 150 mg/Placebo | Sequence 3: LIK066 150 mg/LIK066 50 mg/Placebo/LIK066 15 mg | Sequence 4: Placebo/LIK066 150 mg/LIK066 15 mg/LIK066 50 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.4 Years STANDARD_DEVIATION 9.29 | 54.0 Years STANDARD_DEVIATION 10.54 | 62.3 Years STANDARD_DEVIATION 3.06 | 56.0 Years STANDARD_DEVIATION 8.19 | 56.0 Years STANDARD_DEVIATION 8.26 |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 8 / 14 | 7 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Day 1 and Day 4 (pre-meal, every half hour till 5 hour on Day 1 and Day 4)
Population: The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LIK066 15 mg | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 1 | 101.97 (umol/kg FFM/min)*hr | Standard Deviation 29.348 |
| LIK066 15 mg | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 4 | 109.99 (umol/kg FFM/min)*hr | Standard Deviation 27.144 |
| LIK066 50 mg | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 4 | 117.81 (umol/kg FFM/min)*hr | Standard Deviation 30.881 |
| LIK066 50 mg | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 1 | 93.89 (umol/kg FFM/min)*hr | Standard Deviation 25.852 |
| LIK066 150 mg | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 1 | 63.84 (umol/kg FFM/min)*hr | Standard Deviation 22.589 |
| LIK066 150 mg | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 4 | 112.45 (umol/kg FFM/min)*hr | Standard Deviation 31.129 |
| Placebo | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 1 | 97.76 (umol/kg FFM/min)*hr | Standard Deviation 30.615 |
| Placebo | Area Under the Postprandial Curve (AUC) for Rate of Appearance (Ra) of Exogenous Glucose | Day 4 | 103.97 (umol/kg FFM/min)*hr | Standard Deviation 23.335 |