Elevated Body Mass Index
Conditions
Keywords
dysglycemic, normoglycemic, prediabetes, type 2 diabetes mellitus
Brief summary
A 12-week study to assess LIK066 effect on body weight in diabetics, prediabetics and normoglycemic patients with elevated body mass index (BMI)
Interventions
DRUGLIK066
LIK066 25 mg tablets
DRUGPlacebo
Matching placebo tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Subjects with stable health condition as determined by past medical history, physical examination, electrocardiogram, and laboratory tests at screening. * Patients with dysglycemia are patients with: Fasting plasma glucose \>100mg/dL (5.6 mmol/L), or HbA1c \> 5.7% and \< 10% at screening. * Fasting plasma glucose ≤250mg/dL (13.9 mmol/L) at screening. * If treated with antidiabetic medications (other than prohibited medications), patients must be on a stable dose for 12 weeks prior to randomization and maintain the dose until the end of the study. * Subjects must have a body mass index (BMI) within the range of 35 - 50 kg/m2 at screening, with stable body weight (± 5 kg) within 3 months prior to screening Key
Exclusion criteria
* Pre-existing, clinically significant gastrointestinal, liver, cardiovascular, renal or other chronic medical condition which is considered serious or unstable, other than stable cardiovascular disease, treated hypertension, dyslipidemia or other stable chronic disorders * Clinically significant GI disorder related to malabsorption or that may affect drug or glucose absorption or history of significant gastrointestinal surgery that could affect intestinal glucose absorption * Enrollment in a diet, weight loss or exercise programs with the specific intent of losing weight, within 3 months prior to randomization, or clinical diagnosis of any eating disorder * Pregnant or nursing (lactating) women, and women of child-bearing potential
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percent Change in Body Weight From Baseline to Week 12 | Baseline, Week 12 (Day 85) | Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is Day -1 in Part 1. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by- time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, and the treatment-by-time-by-glycemic status interaction, and Baseline body weight as a covariate. |
| Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | 12 weeks | This endpoint reports patients with at least one AE (any AE), serious AE and death. |
| Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) | Baseline, Week 2 (Day 14) | Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Part 1: Baseline is defined as Day -1. Part 2: Baseline is defined as Day 1 predose. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate. |
| Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | 2 weeks | This endpoint reports patients with at least one AE (any AE), serious AE and death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms | Baseline, Week 2 | Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is defined as Day 1 predose. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate. |
| Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study | Day 84 | Blood samples were collected at predose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h postdose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. |
| Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study | Day 84 | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. |
| Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study | Day 84 | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. |
| Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 1, Day 14 | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Tmax at steady state (Tmax, ss) |
| Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study | Day 84 | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. |
| The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study | Day 84 | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. |
| The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study | Day 84 | Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. |
| Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 1, Day 14 | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Cmax at steady state (Cmax, ss) |
| Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 1, Day 14 | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUClast at steady state (AUClast, ss) |
| Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 1, Day 14 | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUCtau at steady state (AUCtau, ss) |
| The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 1, Day 14 | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports CLss/F at steady state (CLss/F, ss) |
| The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 1, Day 14 | Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Vz/F at steady state (Vz/F, ss) |
Countries
United States
Participant flow
Pre-assignment details
Subjects were stratified by their glycemic status (dysglycemic or normoglycemic) and randomized to LIK066 or placebo within each stratum in each part of the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) LIK066 150 mg qd within 15 minutes before starting lunch | 44 |
| Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch. | 44 |
| Part 2: LIK066 75 mg Twice Daily (Bid) LIK066 75 mg bid before breakfast and dinner | 40 |
| Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals; | 43 |
| Part 2: Placebo Three Times Daily Matching placebo tablets tid before meals. | 10 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Subject/guardian decision | 1 | 0 | 0 | 4 | 0 |
Baseline characteristics
| Characteristic | Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Placebo Once Daily | Part 2: LIK066 75 mg Twice Daily (Bid) | Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Placebo Three Times Daily | Total |
|---|---|---|---|---|---|---|
| Age, Continuous Part 1 (44, 44, NA,NA,NA,88) | 39.0 Years STANDARD_DEVIATION 12.01 | 41.3 Years STANDARD_DEVIATION 11.07 | NA Years | NA Years | NA Years | 40.2 Years STANDARD_DEVIATION 11.54 |
| Age, Continuous Part 2 (NA, NA, 40,43,10,93) | NA Years | NA Years | 42.9 Years STANDARD_DEVIATION 8.96 | 39.9 Years STANDARD_DEVIATION 11.22 | 43.4 Years STANDARD_DEVIATION 12.39 | 41.6 Years STANDARD_DEVIATION 10.44 |
| Sex: Female, Male Female | 19 Participants | 26 Participants | 26 Participants | 26 Participants | 8 Participants | 105 Participants |
| Sex: Female, Male Male | 25 Participants | 18 Participants | 14 Participants | 17 Participants | 2 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 43 / 44 | 39 / 44 | 40 / 40 | 43 / 43 | 10 / 10 |
| serious Total, serious adverse events | 1 / 44 | 0 / 44 | 0 / 40 | 0 / 43 | 0 / 10 |
Outcome results
Primary
Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14)
Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Part 1: Baseline is defined as Day -1. Part 2: Baseline is defined as Day 1 predose. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate.
Time frame: Baseline, Week 2 (Day 14)
Population: Pharmacodynamic set. The analysis was based on all subjects with a baseline body weight and at least one post-Baseline body weight measurement. Only data from common time points in Part 1 and Part 2 were included in the analysis, i.e., Baseline and Day 14.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) | -1.17 Percent change |
| Part 1: Placebo Once Daily | Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) | -1.73 Percent change |
| Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) | -1.71 Percent change |
| Part 1 and 2 : Pooled Placebo | Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) | 0.66 Percent change |
Comparison: This analysis on all subjects. The following criteria were assessed:~1. upper confidence limit of 80% CI for treatment difference was less than 0, and~2. estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%.p-value: <0.00180% CI: [-2.16, -1.51]Mixed Models Analysis
Comparison: This analysis on all subjects. The following criteria were assessed:~1. upper confidence limit of 80% CI for treatment difference was less than 0, and~2. estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%.p-value: <0.00180% CI: [-2.94, -1.84]Mixed Models Analysis
Comparison: This analysis on all subjects. The following criteria were assessed:~1. upper confidence limit of 80% CI for treatment difference was less than 0, and~2. estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%p-value: <0.00180% CI: [-2.93, -1.83]Mixed Models Analysis
Primary
Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death
This endpoint reports patients with at least one AE (any AE), serious AE and death.
Time frame: 12 weeks
Population: The safety analysis set included all subjects that received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | With at least one AE (any AE) | 43 Patients |
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Serious AE | 1 Patients |
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
| Part 1: Placebo Once Daily | Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | With at least one AE (any AE) | 39 Patients |
| Part 1: Placebo Once Daily | Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Serious AE | 0 Patients |
| Part 1: Placebo Once Daily | Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
Primary
Part 1: Percent Change in Body Weight From Baseline to Week 12
Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is Day -1 in Part 1. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by- time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, and the treatment-by-time-by-glycemic status interaction, and Baseline body weight as a covariate.
Time frame: Baseline, Week 12 (Day 85)
Population: The pharmacodynamics (PD) analysis set included all subjects with available PD data and no protocol deviations with relevant impact on PD data. The analysis is based on all subjects with a Baseline body weight and at least one post-Baseline body weight measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Percent Change in Body Weight From Baseline to Week 12 | All subjects (n= 42, 43) | -5.51 percent change |
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Percent Change in Body Weight From Baseline to Week 12 | Dysglycemic subjects (n= 22, 23) | -6.55 percent change |
| Part 1: LIK066 150 mg Once Daily (qd) | Part 1: Percent Change in Body Weight From Baseline to Week 12 | Normoglycemic subjects (n= 20,20) | -4.46 percent change |
| Part 1: Placebo Once Daily | Part 1: Percent Change in Body Weight From Baseline to Week 12 | All subjects (n= 42, 43) | 0.19 percent change |
| Part 1: Placebo Once Daily | Part 1: Percent Change in Body Weight From Baseline to Week 12 | Dysglycemic subjects (n= 22, 23) | 0.29 percent change |
| Part 1: Placebo Once Daily | Part 1: Percent Change in Body Weight From Baseline to Week 12 | Normoglycemic subjects (n= 20,20) | 0.09 percent change |
Comparison: This analysis included all subjects. The following criteria were assessed:~1. upper confidence limit of the 80% CI for treatment difference (LIK066 - placebo) was less than 0, and~2. estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%.p-value: <0.00180% CI: [-6.52, -4.87]Mixed Models Analysis
Comparison: This analysis included dysglycemic subjects. The following criteria were assessed:~1. upper confidence limit of 80% CI for treatment difference was less than 0, and~2. estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%.p-value: <0.00180% CI: [-7.96, -5.73]Mixed Models Analysis
Comparison: This analysis included normoglycemic subjects. The following criteria were assessed:~1. upper confidence limit of 80% CI for treatment difference was less than 0, and~2. estimated mean treatment difference was less than or equal to -5%. The first criterion addressed whether, with high certainty, there was superior weight loss in LIK066 treated group compared to placebo. The second criterion addressed whether observed mean reduction in body weight over placebo was at least 5%.p-value: <0.00180% CI: [-5.76, -3.34]Mixed Models Analysis
Primary
Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death
This endpoint reports patients with at least one AE (any AE), serious AE and death
Time frame: 2 weeks
Population: The safety analysis set included all subjects that received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Serious AE | 0 Patients |
| Part 1: LIK066 150 mg Once Daily (qd) | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | At least one AE (Any AE) | 40 Patients |
| Part 1: LIK066 150 mg Once Daily (qd) | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
| Part 1: Placebo Once Daily | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Serious AE | 0 Patients |
| Part 1: Placebo Once Daily | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | At least one AE (Any AE) | 43 Patients |
| Part 1: Placebo Once Daily | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
| Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | At least one AE (Any AE) | 10 Patients |
| Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
| Part 2: LIK066 50 mg Three Times Daily (Tid) | Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death | Serious AE | 0 Patients |
Secondary
Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation.
Time frame: Day 84
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study | Dysglycemic (n=22) | 11600 hr*ng/mL | Standard Deviation 3260 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study | Normoglycemic (n=18) | 12800 hr*ng/mL | Standard Deviation 4860 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing at Steady State (AUCtau, ss) of LIK066 in Part 1 of the Study | Overall (n=40) | 12100 hr*ng/mL | Standard Deviation 4050 |
Secondary
Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUCtau at steady state (AUCtau, ss)
Time frame: Day 1, Day 14
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 3170 hr*ng/mL | Standard Deviation 573 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 1, Normoglycemic (n= 18, 19) | 3290 hr*ng/mL | Standard Deviation 699 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 1, Overall (n= 37, 39) | 3230 hr*ng/mL | Standard Deviation 632 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 4620 hr*ng/mL | Standard Deviation 1060 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 4310 hr*ng/mL | Standard Deviation 1160 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 4470 hr*ng/mL | Standard Deviation 1100 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 2000 hr*ng/mL | Standard Deviation 586 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 1340 hr*ng/mL | Standard Deviation 295 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 1940 hr*ng/mL | Standard Deviation 600 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 1, Normoglycemic (n= 18, 19) | 1350 hr*ng/mL | Standard Deviation 429 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 1970 hr*ng/mL | Standard Deviation 586 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of Next Dosing (AUCtau) of LIK066 in Part 2 of the Study | Day 1, Overall (n= 37, 39) | 1350 hr*ng/mL | Standard Deviation 362 |
Secondary
Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation.
Time frame: Day 84
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study | Dysglycemic (n=22) | 11600 hr*ng/mL | Standard Deviation 3260 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study | Normoglycemic (n=18) | 12800 hr*ng/mL | Standard Deviation 4860 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration at Steady State (AUClast, ss) of LIK066 in Part 1 of the Study | Overall (n=40) | 12100 hr*ng/mL | Standard Deviation 4050 |
Secondary
Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. The linear trapezoidal rule was used for AUC calculation. Day 14 data reports AUClast at steady state (AUClast, ss)
Time frame: Day 1, Day 14
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 3160 hr*ng/mL | Standard Deviation 571 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 1, Normoglycemic (n= 19, 19) | 3280 hr*ng/mL | Standard Deviation 674 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 1, Overall (n= 38, 39) | 3220 hr*ng/mL | Standard Deviation 619 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 4600 hr*ng/mL | Standard Deviation 1050 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 4300 hr*ng/mL | Standard Deviation 1160 |
| Part 1: LIK066 150 mg Once Daily (qd) | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 4450 hr*ng/mL | Standard Deviation 1100 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 4950 hr*ng/mL | Standard Deviation 1580 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 3910 hr*ng/mL | Standard Deviation 840 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 4740 hr*ng/mL | Standard Deviation 1200 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 1, Normoglycemic (n= 19, 19) | 3870 hr*ng/mL | Standard Deviation 1360 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 4850 hr*ng/mL | Standard Deviation 1390 |
| Part 1: Placebo Once Daily | Area Under the Plasma Concentration-time Profile to the Time of the Last Quantifiable Concentration (AUClast) of LIK066 in Part 2 of the Study | Day 1, Overall (n= 38, 39) | 3890 hr*ng/mL | Standard Deviation 1110 |
Secondary
Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study
Blood samples were collected at predose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h postdose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.
Time frame: Day 84
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study | Dysglycemic (n=22) | 1230 ng/mL | Standard Deviation 328 |
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study | Normoglycemic (n=18) | 1220 ng/mL | Standard Deviation 327 |
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 at Steady State (Cmax ss) in Part 1 of the Study | Overall (n=40) | 1230 ng/mL | Standard Deviation 323 |
Secondary
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Cmax at steady state (Cmax, ss)
Time frame: Day 1, Day 14
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 1100 ng/mL | Standard Deviation 361 |
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 1, Normoglycemic (n= 19, 19) | 767 ng/mL | Standard Deviation 275 |
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 1030 ng/mL | Standard Deviation 266 |
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 728 ng/mL | Standard Deviation 274 |
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 1070 ng/mL | Standard Deviation 315 |
| Part 1: LIK066 150 mg Once Daily (qd) | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 1, Overall (n= 38, 39) | 747 ng/mL | Standard Deviation 272 |
| Part 1: Placebo Once Daily | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 754 ng/mL | Standard Deviation 278 |
| Part 1: Placebo Once Daily | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 513 ng/mL | Standard Deviation 176 |
| Part 1: Placebo Once Daily | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 1, Normoglycemic (n= 19, 19) | 517 ng/mL | Standard Deviation 223 |
| Part 1: Placebo Once Daily | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 716 ng/mL | Standard Deviation 282 |
| Part 1: Placebo Once Daily | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 792 ng/mL | Standard Deviation 276 |
| Part 1: Placebo Once Daily | Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study | Day 1, Overall (n= 38, 39) | 515 ng/mL | Standard Deviation 198 |
Secondary
Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms
Triplicate body weight measurements at each visit were averaged and represented body weight at that visit. Baseline was defined to be the body weight at the last visit prior to the first treatment. Baseline is defined as Day 1 predose. Percent change is calculated as \[(post baseline- Baseline) /Baseline\] \* 100. A longitudinal mixed effects model for percent change in body weight was used. The longitudinal mixed effects model included fixed effects of treatment, time, glycemic status (a stratification factor for randomization), the treatment-by-time interaction, the treatment-by-glycemic status interaction, the time-by-glycemic status interaction, the treatment-by-time-by-glycemic status interaction, a random effect for study part and baseline body weight as a covariate.
Time frame: Baseline, Week 2
Population: The pharmacodynamics (PD) analysis set included all subjects with available PD data and no protocol deviations with relevant impact on PD data. The analysis is based on all subjects with a Baseline body weight and at least one post-Baseline body weight measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms | Dysglycemic (n= 20, 19) | -1.99 percent change |
| Part 1: LIK066 150 mg Once Daily (qd) | Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms | Normoglycemic (n=20, 20) | -1.46 percent change |
| Part 1: Placebo Once Daily | Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms | Dysglycemic (n= 20, 19) | -1.73 percent change |
| Part 1: Placebo Once Daily | Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14) in LIK066 Twice Daily and LIK066 Three Times Daily Arms | Normoglycemic (n=20, 20) | -1.70 percent change |
Secondary
The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports CLss/F at steady state (CLss/F, ss)
Time frame: Day 1, Day 14
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 24.3 Liter/hour | Standard Deviation 3.97 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 1, Normoglycemic (n= 18, 19) | 23.8 Liter/hour | Standard Deviation 5.28 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 1, Overall (n= 37, 39) | 24.1 Liter/hour | Standard Deviation 4.59 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 17.1 Liter/hour | Standard Deviation 4.05 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 18.5 Liter/hour | Standard Deviation 4.72 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 17.8 Liter/hour | Standard Deviation 4.4 |
| Part 1: Placebo Once Daily | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 27.2 Liter/hour | Standard Deviation 8.5 |
| Part 1: Placebo Once Daily | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 39.3 Liter/hour | Standard Deviation 9.42 |
| Part 1: Placebo Once Daily | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 27.8 Liter/hour | Standard Deviation 7.35 |
| Part 1: Placebo Once Daily | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 1, Normoglycemic (n= 18, 19) | 40.5 Liter/hour | Standard Deviation 12.8 |
| Part 1: Placebo Once Daily | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 27.5 Liter/hour | Standard Deviation 7.84 |
| Part 1: Placebo Once Daily | The Apparent Systemic Clearance at Steady State (CLss/F) of LIK066 Following Extra Vascular Administration in Part 2 of the Study | Day 1, Overall (n= 37, 39) | 39.9 Liter/hour | Standard Deviation 11.1 |
Secondary
The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.
Time frame: Day 84
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study | Dysglycemic (n=22) | 14.1 Liter/hour | Standard Deviation 4.67 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study | Normoglycemic (n=18) | 13.2 Liter/hour | Standard Deviation 4.42 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Systemic Clearance at Steady State (CLss/F, ss) of LIK066 Following Extra Vascular Administration in Part 1 of the Study | Overall (n=40) | 13.7 Liter/hour | Standard Deviation 4.52 |
Secondary
The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.
Time frame: Day 84
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study | Dysglycemic (n=14) | 110 Liter | Standard Deviation 23.8 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study | Normoglycemic (n=8) | 106 Liter | Standard Deviation 31.2 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration at Steady State (Vz/F, ss) in Part 1 of the Study | Overall (n=22) | 109 Liter | Standard Deviation 26.1 |
Secondary
The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Vz/F at steady state (Vz/F, ss)
Time frame: Day 1, Day 14
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 19) | 132 Liter | Standard Deviation 51.7 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 1, Normoglycemic (n= 18, 17) | 127 Liter | Standard Deviation 42.4 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 1, Overall (n= 37, 36) | 130 Liter | Standard Deviation 46.8 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 16) | 108 Liter | Standard Deviation 52.5 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 112 Liter | Standard Deviation 34.1 |
| Part 1: LIK066 150 mg Once Daily (qd) | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 14, Overall (n= 40, 35) | 110 Liter | Standard Deviation 43.7 |
| Part 1: Placebo Once Daily | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 267 Liter | Standard Deviation 493 |
| Part 1: Placebo Once Daily | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 19) | 274 Liter | Standard Deviation 224 |
| Part 1: Placebo Once Daily | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 16) | 580 Liter | Standard Deviation 1380 |
| Part 1: Placebo Once Daily | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 1, Normoglycemic (n= 18, 17) | 519 Liter | Standard Deviation 1330 |
| Part 1: Placebo Once Daily | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 14, Overall (n= 40, 35) | 410 Liter | Standard Deviation 997 |
| Part 1: Placebo Once Daily | The Apparent Volume of Distribution of LIK066 During the Terminal Elimination Phase Following Extra Vascular Administration (Vz/F) in Part 2 of the Study | Day 1, Overall (n= 37, 36) | 390 Liter | Standard Deviation 919 |
Secondary
Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 24 h post-dose on Day 84. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects.
Time frame: Day 84
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study | Dysglycemic (n=22) | 3.02 hour |
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study | Normoglycemic (n=18) | 4.02 hour |
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study | Overall (n=40) | 3.02 hour |
Secondary
Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study
Blood samples were collected at pre-dose, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 9 h post-dose on Day 1 and 14. Overall glycemic status represents combination of dysglycemic and normoglycemic subjects. Day 14 data reports Tmax at steady state (Tmax, ss)
Time frame: Day 1, Day 14
Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 1.00 hour | Full Range 274 |
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 1, Normoglycemic (n= 19, 19) | 1.00 hour | Full Range 275 |
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 1, Overall (n= 38, 39) | 1.00 hour | Full Range 272 |
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 0.983 hour | Full Range 361 |
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 1.00 hour | Full Range 266 |
| Part 1: LIK066 150 mg Once Daily (qd) | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 0.992 hour | Full Range 315 |
| Part 1: Placebo Once Daily | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 14, Normoglycemic (n= 20, 19) | 0.533 hour | Full Range 276 |
| Part 1: Placebo Once Daily | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 1, Dysglycemic (n= 19, 20) | 1.00 hour | Full Range 176 |
| Part 1: Placebo Once Daily | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 14, Dysglycemic (n= 20, 19) | 1.00 hour | Full Range 282 |
| Part 1: Placebo Once Daily | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 1, Normoglycemic (n= 19, 19) | 0.983 hour | Full Range 223 |
| Part 1: Placebo Once Daily | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 14, Overall (n= 40, 38) | 1.00 hour | Full Range 278 |
| Part 1: Placebo Once Daily | Time to Maximum Plasma Concentration of LIK066 (Tmax) in Part 2 of the Study | Day 1, Overall (n= 38, 39) | 1.00 hour | Full Range 198 |