Obesity, Overweight
Conditions
Keywords
Obesity, Overweight
Brief summary
This was a dose-finding study that evaluated the change in weight after 24 weeks treatment with 8 different doses of LIK066 compared to placebo in obese or overweight adults, followed by 24 weeks treatment with 2 doses of LIK066 and placebo.
Interventions
DRUGLIK066
LIK066 will be supplied in different doses as tablets to be taken orally.
DRUGPlacebo
Placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. informed consent 2. (BMI\>=30) or (BMI\>=27 with history of CV disease, hypertension, dyslipidemia, pre-diabetes or type 2 diabetes mellitus, sleep-apnea syndrome) 3. willing to comply with life-style intervention and treatment during the full duration of the study (approximately 54 weeks)
Exclusion criteria
* Hypersensitivity to any of the study medications * Pregnancy or lactating women * History of malignancies * Use of pharmacologically active weight loss products * Bariatric surgery * Ketoacidosis, lactic acidosis, hyperosmolar coma in the 6 months before the screening visit. * HbA1c \>10% at the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at 24 Weeks | Baseline, Week 24 (Epoch 3) | Dose-response relationship of two dose regimens of LIK066 as measured by the percent change from baseline in body weight relative to placebo after 24 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Baseline, Week 24 | Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline for dysglycemic, normoglycemic, Type 2 Diabetes Mellitus (T2DM) |
| Percentage Change From Baseline on Waist Circumference | Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4) | Waist circumference will be measured to the nearest 0.1cm in a standing position, at the end of a normal expiration, using a tape at the level of the iliac crest. |
| Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4) | FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake). |
| Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | Baseline, Week 24 (Epoch 3), Week 24 to week 48 (Epoch 4) | HbA1c will be measured from a blood sample obtained at indicated visits and will be analyzed at a central laboratory. |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline, Week 24 (Epoch 3) Week 24 to Week 48 (Epoch 4) | At each study visit (baseline, week 24, Week 48), after the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP and DBP will be measured |
| Change From Baseline in 24-hour Urinary Glucose Excretion | Baseline, week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4) | Urinary glucose excretion will be measured from 24-hour urinary collection at indicated visits and will be analyzed at a central laboratory. |
| Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4) | Between Week 24 and Week 48 (Epoch 4) | Between -treatment analysis of percentage change from Week 24 in body weight (kg) at Week 48 (Epoch 4) |
| Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline, Week 24 | Evaluation of 24-hour urinary calcium excretion after 24 week of treatment. |
| Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Baseline, Week 24, Week 48 | Evaluation of 24-hour urinary calcium after 48 weeks of treatment |
| Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | Baseline, Week 24 | Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline |
| Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 24, Week 48 | Evaluation of 24-hour urinary phosphorus excretion after 48 weeks of treatment |
| Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Baseline, Week 24, Week 24 to Week 48 (Epoch 4) | Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48 |
| Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | Baseline to Week 24, Week 24 to Week 48 (Epoch 4) | Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48 |
| Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Baseline to Week 24, Week 24 to Week 48 (Epoch 4) | Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48 |
| Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | Summary at Week 24 from qd or bid regimens | Observe maximum plasma concentration following administration of LIK066 (Cmax) |
| Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | Summary at Week 24 for qd or bid regimens | Time to reach the maximum concentration after administration of LIK066 (Tmax) |
| Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | Summary at Week 24 from qd or bid regimens (0-6h) | Area under the plasma concentration-time curve from time zero time 't' where t is a defined time point after administration (AUC0-t) |
| Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | Summary at Week 24 from qd or bid regimens | Last non-zero concentration area under the curve (AUClast) |
| Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24, Week 48 | Evaluation of 24-hour urinary phosphorus excretion after 24 weeks of treatment |
Countries
Austria, Canada, Czechia, Hungary, Slovakia, United Kingdom, United States
Participant flow
Recruitment details
Overall, 674 patients were screened. Of the 460 patients who were randomized to the study, the majority (85.7%) completed Epoch 3. Of the 394 patients who completed Epoch 3 and entered Epoch 4, the majority (93.1%) completed the Epoch 4 study period.
Pre-assignment details
Overall, 674 patients were screened. Of the 460 patients who were randomized to the study, the majority (85.7%) completed Epoch 3. Of the 394 patients who completed Epoch 3 and entered Epoch 4, the majority (93.1%) completed the Epoch 4 study period.
Participants by arm
| Arm | Count |
|---|---|
| LIK066 2.5mg qd (Epoch 3) LIK066 2.5mg qd (once daily) dosing frequency for 24 weeks | 38 |
| LIK066 10mg qd (Epoch 3) LIK066 10mg qd (once daily) dosing frequency for 24 weeks | 38 |
| LIK066 50mg qd (Epoch 3) LIK066 50mg qd (once daily) dosing frequency for 24 weeks | 38 |
| LIK066 150mg qd (Epoch 3) LIK066 150mg qd (once daily) dosing frequency for 24 weeks | 77 |
| LIK066 2.5mg Bid (Epoch 3) LIK066 2.5mg bid (twice daily) dosing frequency for 24 weeks | 38 |
| LIK066 5mg Bid (Epoch 3) LIK066 5mg bid (twice daily) dosing frequency for 24 weeks | 39 |
| LIK066 25mg Bid (Epoch 3) LIK066 25mg bid (twice daily) dosing frequency for 24 weeks | 38 |
| LIK066 50mg Bid (Epoch 3) LIK066 50mg bid (twice daily) dosing frequency for 24 weeks | 76 |
| Placebo (Epoch 3) Matching placebo tablets for 24 weeks | 78 |
| Total | 460 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Epoch 3 (24 Weeks of Treatment) | Adverse Event | 0 | 0 | 4 | 8 | 1 | 0 | 3 | 11 | 2 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Non-compliance with study treatment | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Epoch 3 (24 Weeks of Treatment) | Withdrawal by Subject | 2 | 4 | 3 | 4 | 1 | 1 | 1 | 4 | 2 | 0 | 0 | 0 | 0 |
| Epoch 4 (Last 24 Weeks of the Study) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 7 | 0 | 2 |
| Epoch 4 (Last 24 Weeks of the Study) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Epoch 4 (Last 24 Weeks of the Study) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 0 |
| Epoch 4 (Last 24 Weeks of the Study) | non-compliance with study treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Epoch 4 (Last 24 Weeks of the Study) | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Epoch 4 (Last 24 Weeks of the Study) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 2 | 1 |
Baseline characteristics
| Characteristic | LIK066 2.5mg qd (Epoch 3) | Total | Placebo (Epoch 3) | LIK066 50mg Bid (Epoch 3) | LIK066 25mg Bid (Epoch 3) | LIK066 5mg Bid (Epoch 3) | LIK066 2.5mg Bid (Epoch 3) | LIK066 150mg qd (Epoch 3) | LIK066 50mg qd (Epoch 3) | LIK066 10mg qd (Epoch 3) |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.3 Years STANDARD_DEVIATION 12.2 | 51.7 Years STANDARD_DEVIATION 12.31 | 51.1 Years STANDARD_DEVIATION 13.27 | 52.9 Years STANDARD_DEVIATION 11.87 | 49.7 Years STANDARD_DEVIATION 11.93 | 49.8 Years STANDARD_DEVIATION 11.5 | 53.4 Years STANDARD_DEVIATION 12.28 | 51.1 Years STANDARD_DEVIATION 12.94 | 52.9 Years STANDARD_DEVIATION 13.6 | 53.2 Years STANDARD_DEVIATION 10.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 6 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 10 Participants | 1 Participants | 5 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 42 Participants | 8 Participants | 6 Participants | 4 Participants | 3 Participants | 2 Participants | 5 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 7 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 30 Participants | 392 Participants | 64 Participants | 63 Participants | 34 Participants | 32 Participants | 36 Participants | 67 Participants | 33 Participants | 33 Participants |
| Sex: Female, Male Female | 23 Participants | 283 Participants | 45 Participants | 49 Participants | 26 Participants | 24 Participants | 20 Participants | 44 Participants | 25 Participants | 27 Participants |
| Sex: Female, Male Male | 15 Participants | 177 Participants | 33 Participants | 27 Participants | 12 Participants | 15 Participants | 18 Participants | 33 Participants | 13 Participants | 11 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 1 / 38 | 0 / 38 | 0 / 77 | 1 / 38 | 0 / 39 | 0 / 38 | 0 / 76 | 0 / 40 | 0 / 38 |
| other Total, other adverse events | 33 / 38 | 24 / 38 | 24 / 38 | 55 / 77 | 31 / 38 | 32 / 39 | 26 / 38 | 47 / 76 | 32 / 40 | 32 / 38 |
| serious Total, serious adverse events | 3 / 38 | 3 / 38 | 1 / 38 | 3 / 77 | 5 / 38 | 2 / 39 | 2 / 38 | 1 / 76 | 1 / 40 | 4 / 38 |
Outcome results
Primary
Percent Change From Baseline in Body Weight at 24 Weeks
Dose-response relationship of two dose regimens of LIK066 as measured by the percent change from baseline in body weight relative to placebo after 24 weeks of treatment
Time frame: Baseline, Week 24 (Epoch 3)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -1.24 Percent change |
| LIK066 10mg qd (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -2.04 Percent change |
| LIK066 50mg qd (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -3.52 Percent change |
| LIK066 150mg qd (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -4.37 Percent change |
| LIK066 2.5mg Bid (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -1.67 Percent change |
| LIK066 5mg Bid (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -2.51 Percent change |
| LIK066 25mg Bid (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -4.06 Percent change |
| LIK066 50mg Bid (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -4.47 Percent change |
| Placebo (Epoch 3) | Percent Change From Baseline in Body Weight at 24 Weeks | -0.63 Percent change |
p-value: <0.000195% CI: [-3.17, -0.29]ANCOVA
p-value: <0.000195% CI: [-3.36, -0.5]ANCOVA
p-value: <0.000195% CI: [-4.86, -1.75]ANCOVA
p-value: <0.000195% CI: [-5.39, -3.44]ANCOVA
p-value: <0.000195% CI: [-2.53, -0.25]ANCOVA
p-value: <0.000195% CI: [-4.11, -1.36]ANCOVA
p-value: <0.000195% CI: [-5.54, -2.68]ANCOVA
p-value: <0.000195% CI: [-5.54, -3.43]ANCOVA
Secondary
Change From Baseline in 24-hour Urinary Glucose Excretion
Urinary glucose excretion will be measured from 24-hour urinary collection at indicated visits and will be analyzed at a central laboratory.
Time frame: Baseline, week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 208.6 mmol/24hr |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 134.6 mmol/24hr |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 377.0 mmol/24hr |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 306.1 mmol/24hr |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 183.0 mmol/24hr |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 193.8 mmol/24hr |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 241.3 mmol/24hr |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | 308.9 mmol/24hr |
| Placebo (Epoch 3) | Change From Baseline in 24-hour Urinary Glucose Excretion | -17.8 mmol/24hr |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in 24-hour Urinary Glucose Excretion | 26.8 mmol/24hr |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in 24-hour Urinary Glucose Excretion | 122.5 mmol/24hr |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in 24-hour Urinary Glucose Excretion | 248.0 mmol/24hr |
| Placebo/Placebo (Epoch 4) | Change From Baseline in 24-hour Urinary Glucose Excretion | -148.9 mmol/24hr |
Secondary
Change From Baseline in Fasting Lipid Profile (Lipoproteins)
Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48
Time frame: Baseline, Week 24, Week 24 to Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 8.9 g/L |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 2.9 g/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 8.13 g/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 7.7 g/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 10.7 g/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 3.3 g/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 8.9 g/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 12.4 g/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | -0.4 g/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 5.3 g/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 4.5 g/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 8.1 g/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 6.7 g/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 2.3 g/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 11.0 g/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 3.9 g/L |
| Placebo (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 6.7 g/L |
| Placebo (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | 5.8 g/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | -1.7 g/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 3.0 g/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | -2.4 g/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 3.4 g/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | 5.6 g/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | -2.3 g/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein B | -2.0 g/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Lipoproteins) | Apoliprotein A1 | -0.7 g/L |
Secondary
Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol)
Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48
Time frame: Baseline to Week 24, Week 24 to Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 0.8 mmol/L |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 6.0 mmol/L |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 8.7 mmol/L |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | -3.8 mmol/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 7.3 mmol/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 4.9 mmol/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 17.5 mmol/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 1.3 mmol/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 5.2 mmol/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 8.2 mmol/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 4.8 mmol/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | -11.5 mmol/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 8.0 mmol/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 21.8 mmol/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 14.6 mmol/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | -3.0 mmol/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 2.3 mmol/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 4.1 mmol/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 1.5 mmol/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 2.9 mmol/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 2.4 mmol/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 1.7 mmol/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 5.1 mmol/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 8.7 mmol/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 7.7 mmol/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 5.5 mmol/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 6.4 mmol/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 1.5 mmol/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 8.8 mmol/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 8.0 mmol/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 10.9 mmol/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | -7.4 mmol/L |
| Placebo (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | 12.5 mmol/L |
| Placebo (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 4.0 mmol/L |
| Placebo (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 0.7 mmol/L |
| Placebo (Epoch 3) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 4.7 mmol/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 0.8 mmol/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 3.9 mmol/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | -0.6 mmol/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 6.7 mmol/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 3.7 mmol/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 12.4 mmol/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | -1.2 mmol/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 0.3 mmol/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 9.2 mmol/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | -0.9 mmol/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | 0.8 mmol/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | -1.4 mmol/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Total Cholesterol (TC) | -1.7 mmol/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | LDL Cholesterol | -3.5 mmol/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | HDL Cholesterol | 0.7 mmol/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Fasting Lipid Profile (Triglycerides/Cholesterol) | Triglycerides (TG) | 4.8 mmol/L |
Comparison: Triglycerides (TG)p-value: 0.25495% CI: [-21.37, 5.65]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.71695% CI: [-17.44, 11.99]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.03895% CI: [-30.3, -0.86]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.21395% CI: [-18.15, 4.06]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.80695% CI: [-15.38, 11.96]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.73995% CI: [-15.8, 11.21]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.83795% CI: [-12.36, 15.26]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.04995% CI: [-22.71, -0.07]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.76495% CI: [-7.22, 9.82]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.57195% CI: [-6.43, 11.63]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.98795% CI: [-9.3, 9.46]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.00695% CI: [2.85, 16.87]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.46395% CI: [-12.03, 5.48]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.92595% CI: [-8.18, 9.01]ANOVA
Comparison: Total Cholesterol (TC)p-value: 0.71195% CI: [-7.19, 10.53]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.26595% CI: [-3.1, 11.26]ANCOVA
Comparison: HDL Cholesterolp-value: 0.99595% CI: [-7.31, 7.36]ANCOVA
Comparison: HDL Cholesterolp-value: 0.28895% CI: [-3.52, 11.81]ANCOVA
Comparison: HDL Cholesterolp-value: 0.26995% CI: [-3.5, 12.5]ANCOVA
Comparison: HDL Cholesterolp-value: 0.01895% CI: [1.23, 13.27]ANCOVA
Comparison: HDL Cholesterolp-value: 0.56595% CI: [-5.32, 9.73]ANCOVA
Comparison: HDL Cholesterolp-value: 0.64995% CI: [-5.67, 9.09]ANCOVA
Comparison: HDL Cholesterolp-value: 0.84795% CI: [-6.87, 8.36]ANCOVA
Comparison: HDL Cholesterolp-value: 0.0295% CI: [1.14, 13.43]ANCOVA
Comparison: LDL Cholesterolp-value: 0.57995% CI: [-17.09, 9.57]ANCOVA
Comparison: LDL Cholesterolp-value: 0.48795% CI: [-9.08, 19.02]ANCOVA
Comparison: LDL Cholesterolp-value: 0.56195% CI: [-18.96, 10.3]ANCOVA
Comparison: LDL Cholesterolp-value: 0.09795% CI: [-1.68, 20.25]ANCOVA
Comparison: LDL Cholesterolp-value: 0.22795% CI: [-22.1, 5.26]ANCOVA
Comparison: LDL Cholesterolp-value: 0.5895% CI: [-17.22, 9.64]ANCOVA
Comparison: LDL Cholesterolp-value: 0.49495% CI: [-18.67, 9.03]ANCOVA
Comparison: LDL Cholesterolp-value: 0.78295% CI: [-12.81, 9.65]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.81695% CI: [-13.82, 17.54]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.34195% CI: [-8.13, 23.42]ANCOVA
Comparison: Triglycerides (TG)p-value: 0.56695% CI: [-25.39, 13.91]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.40595% CI: [-3.38, 8.36]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.51195% CI: [-3.92, 7.87]ANCOVA
Comparison: Total Cholesterol (TC)p-value: 0.50695% CI: [-4.83, 9.79]ANCOVA
Comparison: HDL Cholesterolp-value: 0.39295% CI: [-4.2, 10.7]ANCOVA
Comparison: HDL Cholesterolp-value: 0.42695% CI: [-4.45, 10.53]ANOVA
Comparison: HDL Cholesterolp-value: 0.07195% CI: [-0.72, 17.8]ANCOVA
Comparison: LDL Cholesterolp-value: 0.49895% CI: [-5.56, 11.42]ANCOVA
Comparison: LDL Cholesterolp-value: 0.58695% CI: [-6.17, 10.9]ANCOVA
Comparison: LDL Cholesterolp-value: 0.69695% CI: [-8.47, 12.67]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM)
FPG will be measured from a blood sample obtained after an overnight fast (at least 8h after last evening food intake).
Time frame: Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | 1.9 mmol/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.1 mmol/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -1.2 mmol/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.8 mmol/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.5 mmol/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -1.1 mmol/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.9 mmol/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -1.0 mmol/L |
| Placebo (Epoch 3) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | 0.9 mmol/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.1 mmol/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.3 mmol/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.1 mmol/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Fasting Plasma Glucose (FPG) in Type 2 Diabetes Mellitus Patients (T2DM) | 0.6 mmol/L |
p-value: 0.24795% CI: [-2.62, 0.68]ANCOVA
p-value: 0.22595% CI: [-0.62, 2.61]ANCOVA
p-value: 0.01995% CI: [-3.75, -0.34]ANCOVA
p-value: 0.01595% CI: [-2.96, -0.33]ANCOVA
p-value: 0.10695% CI: [-2.97, 0.29]ANCOVA
p-value: 0.0295% CI: [-3.54, -0.31]ANCOVA
p-value: 0.03595% CI: [-3.44, -0.12]ANCOVA
p-value: 0.00495% CI: [-3.22, -0.61]ANCOVA
Secondary
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM)
HbA1c will be measured from a blood sample obtained at indicated visits and will be analyzed at a central laboratory.
Time frame: Baseline, Week 24 (Epoch 3), Week 24 to week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | 0.1 mmol/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.5 mmol/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.9 mmol/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.7 mmol/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.3 mmol/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.5 mmol/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.6 mmol/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.6 mmol/L |
| Placebo (Epoch 3) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.3 mmol/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | 0.2 mmol/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | 0.0 mmol/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | -0.1 mmol/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Glycated Hemoglobin A1c (HbA1c) in Type 2 Diabetes Mellitus Patients (T2DM) | 0.3 mmol/L |
p-value: 0.08295% CI: [-0.05, 0.79]ANCOVA
p-value: 0.31995% CI: [-0.63, 0.21]ANCOVA
p-value: 0.00895% CI: [-1.05, -0.16]ANCOVA
p-value: 0.01595% CI: [-0.76, -0.08]ANCOVA
p-value: 0.70795% CI: [-0.5, 0.34]ANCOVA
p-value: 0.2895% CI: [-0.65, 0.19]ANCOVA
p-value: 0.08695% CI: [-0.8, 0.05]ANCOVA
p-value: 0.0395% CI: [-0.72, -0.04]ANCOVA
Secondary
Change From Baseline in High Sensitive C-reactive Protein (hsCRP)
Between-treatment analysis of change after 24 weeks of treatment and between Week 24 and Week 48
Time frame: Baseline to Week 24, Week 24 to Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.99 mg/L |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 1.06 mg/L |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 1.31 mg/L |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.98 mg/L |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 1.02 mg/L |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.93 mg/L |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 1.00 mg/L |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.98 mg/L |
| Placebo (Epoch 3) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.92 mg/L |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.95 mg/L |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.93 mg/L |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 0.96 mg/L |
| Placebo/Placebo (Epoch 4) | Change From Baseline in High Sensitive C-reactive Protein (hsCRP) | 1.07 mg/L |
p-value: 0.63295% CI: [0.81, 1.42]ANCOVA
p-value: 0.35295% CI: [0.86, 1.55]ANCOVA
p-value: 0.02795% CI: [1.04, 1.92]ANCOVA
p-value: 0.58795% CI: [0.85, 1.35]ANCOVA
p-value: 0.50895% CI: [0.82, 1.47]ANCOVA
p-value: 0.94595% CI: [0.76, 1.34]ANCOVA
p-value: 0.60295% CI: [0.81, 1.45]ANCOVA
p-value: 0.61295% CI: [0.84, 1.35]ANCOVA
p-value: 0.38295% CI: [0.68, 1.16]ANCOVA
p-value: 0.3195% CI: [0.67, 1.14]ANCOVA
p-value: 0.52595% CI: [0.65, 1.25]ANCOVA
Secondary
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP)
At each study visit (baseline, week 24, Week 48), after the subject has been sitting for 5 minutes with the back supported and both feet placed on the floor, SBP and DBP will be measured
Time frame: Baseline, Week 24 (Epoch 3) Week 24 to Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -1.2 mmHg |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -0.2 mmHg |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -1.5 mmHg |
| LIK066 10mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | 0.1 mmHg |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -4.9 mmHg |
| LIK066 50mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -2.3 mmHg |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -1.2 mmHg |
| LIK066 150mg qd (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -1.3 mmHg |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | 0.8 mmHg |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -0.7 mmHg |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -1.4 mmHg |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | 0.8 mmHg |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -2.6 mmHg |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | 0.3 mmHg |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -1.8 mmHg |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -1.7 mmHg |
| Placebo (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | 1.6 mmHg |
| Placebo (Epoch 3) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | 0.5 mmHg |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -0.6 mmHg |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -0.9 mmHg |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -1.2 mmHg |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -1.6 mmHg |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | -5.6 mmHg |
| Placebo/LIK066 25mg qd (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | -2.0 mmHg |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | diastolic blood pressure (DBP) | 0.6 mmHg |
| Placebo/Placebo (Epoch 4) | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) | systolic blood pressure (SBP) | 0.8 mmHg |
Comparison: SBPp-value: 0.15695% CI: [-6.64, 1.07]ANCOVA
Comparison: SBPp-value: 0.12795% CI: [-7.11, 0.89]ANCOVA
Comparison: SBPp-value: 0.00295% CI: [-10.52, -2.42]ANCOVA
Comparison: SBPp-value: 0.08995% CI: [-5.86, 0.42]ANCOVA
Comparison: SBPp-value: 0.24595% CI: [-6.12, 1.57]ANCOVA
Comparison: SBPp-value: 0.67895% CI: [-4.65, 3.02]ANCOVA
Comparison: SBPp-value: 0.0495% CI: [-8.07, -0.19]ANCOVA
Comparison: SBPp-value: 0.03895% CI: [-6.61, -0.19]ANCOVA
Comparison: DBPp-value: 0.60195% CI: [-3.38, 1.96]ANCOVA
Comparison: DBPp-value: 0.7695% CI: [-3.2, 2.34]ANCOVA
Comparison: DBPp-value: 0.05195% CI: [-5.6, 0.01]ANCOVA
Comparison: DBPp-value: 0.10595% CI: [-3.98, 0.38]ANCOVA
Comparison: DBPp-value: 0.8295% CI: [-2.36, 2.98]ANCOVA
Comparison: DBPp-value: 0.15795% CI: [-4.58, 0.74]ANCOVA
Comparison: DBPp-value: 0.85995% CI: [-2.99, 2.49]ANCOVA
Comparison: DBPp-value: 0.05495% CI: [-4.41, 0.04]ANCOVA
Secondary
Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion
Evaluation of 24-hour urinary calcium excretion after 24 week of treatment.
Time frame: Baseline, Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 49.6 mmol/24hr | Standard Deviation 25.08 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 48.8 mmol/24hr | Standard Deviation 26.59 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 54.2 mmol/24hr | Standard Deviation 29.34 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | 5.4 mmol/24hr | Standard Deviation 22.74 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | 3.9 mmol/24hr | Standard Deviation 19.56 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 33.1 mmol/24hr | Standard Deviation 29.65 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 38.1 mmol/24hr | Standard Deviation 32.2 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 42.0 mmol/24hr | Standard Deviation 29.99 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 39.8 mmol/24hr | Standard Deviation 22.48 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | -0.6 mmol/24hr | Standard Deviation 12.07 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 39.2 mmol/24hr | Standard Deviation 20.24 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 40.2 mmol/24hr | Standard Deviation 21.55 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 34.6 mmol/24hr | Standard Deviation 17.56 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 40.1 mmol/24hr | Standard Deviation 18.2 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 62.8 mmol/24hr | Standard Deviation 34.26 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | 22.8 mmol/24hr | Standard Deviation 28.42 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 51.2 mmol/24hr | Standard Deviation 35.32 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 52.4 mmol/24hr | Standard Deviation 32.78 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 44.7 mmol/24hr | Standard Deviation 26.83 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | -1.2 mmol/24hr | Standard Deviation 7.77 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | 8.7 mmol/24hr | Standard Deviation 18.21 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 43.6 mmol/24hr | Standard Deviation 16.91 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 54.6 mmol/24hr | Standard Deviation 23.77 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 45.9 mmol/24hr | Standard Deviation 15.41 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 37.9 mmol/24hr | Standard Deviation 32.33 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 38.0 mmol/24hr | Standard Deviation 22.13 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | -0.1 mmol/24hr | Standard Deviation 14.39 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 38.0 mmol/24hr | Standard Deviation 22.13 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 48.1 mmol/24hr | Standard Deviation 21.93 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | 4.9 mmol/24hr | Standard Deviation 26.2 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 53.0 mmol/24hr | Standard Deviation 26.95 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 47.9 mmol/24hr | Standard Deviation 23.64 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Baseline | 43.0 mmol/24hr | Standard Deviation 22.63 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 3) | 7.5 mmol/24hr | Standard Deviation 32.91 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 2) | 52.2 mmol/24hr | Standard Deviation 30.75 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Calcium Excretion | Week 24 (Timepoint 1) | 44.7 mmol/24hr | Standard Deviation 23 |
Secondary
Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion
Evaluation of 24-hour urinary phosphorus excretion after 24 weeks of treatment
Time frame: Week 24, Week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 282.1 mmol/24hr | Standard Deviation 128.1 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 284.0 mmol/24hr | Standard Deviation 140.1 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 297.7 mmol/24hr | Standard Deviation 117.4 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | 13.0 mmol/24hr | Standard Deviation 132 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | 55.6 mmol/24hr | Standard Deviation 89.81 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 240.5 mmol/24hr | Standard Deviation 74.64 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 239.7 mmol/24hr | Standard Deviation 80.4 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 295.3 mmol/24hr | Standard Deviation 95.6 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 260.9 mmol/24hr | Standard Deviation 111.1 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | 38.3 mmol/24hr | Standard Deviation 70 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 299.2 mmol/24hr | Standard Deviation 145.5 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 254.5 mmol/24hr | Standard Deviation 105.7 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 291.5 mmol/24hr | Standard Deviation 175.1 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 275.0 mmol/24hr | Standard Deviation 101.3 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 264.7 mmol/24hr | Standard Deviation 74.84 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | -10.2 mmol/24hr | Standard Deviation 103.6 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 317.8 mmol/24hr | Standard Deviation 205.1 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 319.9 mmol/24hr | Standard Deviation 32.78 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 284.0 mmol/24hr | Standard Deviation 117.6 |
| LIK066 2.5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | -2.1 mmol/24hr | Standard Deviation 159.6 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | 95.1 mmol/24hr | Standard Deviation 67.36 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 241.8 mmol/24hr | Standard Deviation 82.75 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 341.6 mmol/24hr | Standard Deviation 109.2 |
| LIK066 5mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 246.5 mmol/24hr | Standard Deviation 84.19 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 260.5 mmol/24hr | Standard Deviation 124.8 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 299.3 mmol/24hr | Standard Deviation 79.06 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | -38.7 mmol/24hr | Standard Deviation 107.8 |
| LIK066 25mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 277.0 mmol/24hr | Standard Deviation 99.67 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 302.5 mmol/24hr | Standard Deviation 121.3 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | -13.2 mmol/24hr | Standard Deviation 153.8 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 289.3 mmol/24hr | Standard Deviation 83.62 |
| LIK066 50mg Bid (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 293.7 mmol/24hr | Standard Deviation 120.7 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Baseline | 297.0 mmol/24hr | Standard Deviation 145.1 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 3) | 44.9 mmol/24hr | Standard Deviation 177.6 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 2) | 352.8 mmol/24hr | Standard Deviation 159.3 |
| Placebo (Epoch 3) | Change From Baseline to Week 24 (Epoch 3) in the 24-hour Urinary Phosphorus Excretion | Week 24 (Timepoint 1) | 307.9 mmol/24hr | Standard Deviation 145.9 |
Secondary
Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion
Evaluation of 24-hour urinary calcium after 48 weeks of treatment
Time frame: Baseline, Week 24, Week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Baseline | 4.8 mmol/24hr | Standard Deviation 3.02 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 1) | 5.1 mmol/24hr | Standard Deviation 307 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 2) | 4.6 mmol/24hr | Standard Deviation 2.33 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 3) | -0.5 mmol/24hr | Standard Deviation 3.41 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 1) | 5.2 mmol/24hr | Standard Deviation 2.95 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 2) | 5.6 mmol/24hr | Standard Deviation 4.55 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 3) | 0.4 mmol/24hr | Standard Deviation 2.81 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Baseline | 5.0 mmol/24hr | Standard Deviation 2.84 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 2) | 5.4 mmol/24hr | Standard Deviation 3.65 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 1) | 4.5 mmol/24hr | Standard Deviation 0.95 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 3) | 0.9 mmol/24hr | Standard Deviation 4.1 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Baseline | 4.6 mmol/24hr | Standard Deviation 0.91 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 3) | -1.8 mmol/24hr | Standard Deviation 3.26 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 1) | 6.6 mmol/24hr | Standard Deviation 4.55 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Baseline | 5.6 mmol/24hr | Standard Deviation 4.07 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Calcium Excretion | Week 48(Timepoint 2) | 4.8 mmol/24hr | Standard Deviation 2.1 |
Secondary
Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion
Evaluation of 24-hour urinary phosphorus excretion after 48 weeks of treatment
Time frame: Week 24, Week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Baseline | 27.6 mmol/24hr | Standard Deviation 11.46 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 1) | 27.5 mmol/24hr | Standard Deviation 11.73 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 2) | 24.7 mmol/24hr | Standard Deviation 12.74 |
| LIK066 2.5mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48(Timepoint 3) | -2.8 mmol/24hr | Standard Deviation 11.44 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 1) | 30.2 mmol/24hr | Standard Deviation 11.85 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 2) | 31.1 mmol/24hr | Standard Deviation 16.21 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48(Timepoint 3) | 0.9 mmol/24hr | Standard Deviation 14.52 |
| LIK066 10mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Baseline | 30.5 mmol/24hr | Standard Deviation 11.63 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 2) | 31.0 mmol/24hr | Standard Deviation 14.67 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 1) | 28.6 mmol/24hr | Standard Deviation 14.11 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48(Timepoint 3) | 2.4 mmol/24hr | Standard Deviation 17.33 |
| LIK066 50mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Baseline | 28.6 mmol/24hr | Standard Deviation 14.11 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48(Timepoint 3) | -15.5 mmol/24hr | Standard Deviation 18.92 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 1) | 44.4 mmol/24hr | Standard Deviation 17.6 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Baseline | 40.2 mmol/24hr | Standard Deviation 15.96 |
| LIK066 150mg qd (Epoch 3) | Change From Baseline Week 24 to Week 48 (Epoch 4) in the 24-hour Urinary Phosphorus Excretion | Week 48 (Timepoint 2) | 29.0 mmol/24hr | Standard Deviation 15.42 |
Secondary
Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study
Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline
Time frame: Baseline, Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 26.3 Percentage |
| LIK066 2.5mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 5.3 Percentage |
| LIK066 10mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 5.3 Percentage |
| LIK066 10mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 15.8 Percentage |
| LIK066 50mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 5.3 Percentage |
| LIK066 50mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 34.2 Percentage |
| LIK066 150mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 42.9 Percentage |
| LIK066 150mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 6.5 Percentage |
| LIK066 2.5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 15.8 Percentage |
| LIK066 2.5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 5.3 Percentage |
| LIK066 5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 2.6 Percentage |
| LIK066 5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 20.5 Percentage |
| LIK066 25mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 37.8 Percentage |
| LIK066 25mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 10.8 Percentage |
| LIK066 50mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 45.3 Percentage |
| LIK066 50mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 9.3 Percentage |
| Placebo (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=5% | 12.8 Percentage |
| Placebo (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Overall Study | >=10% | 3.8 Percentage |
Comparison: \>=5%p-value: 0.09995% CI: [0.85, 6.67]ANCOVA
Comparison: \>=5%p-value: 0.77995% CI: [0.36, 3.84]ANCOVA
Comparison: \>=5%p-value: 0.01195% CI: [1.35, 10.11]ANCOVA
Comparison: \>=5%p-value: <0.00195% CI: [2.41, 12.88]ANCOVA
Comparison: \>=5%p-value: 0.81295% CI: [0.36, 3.74]ANCOVA
Comparison: \>=5%p-value: 0.22995% CI: [0.66, 5.69]ANCOVA
Comparison: \>=5%p-value: 0.00495% CI: [1.61, 11.46]ANCOVA
Comparison: \>=5%p-value: <0.00195% CI: [2.72, 14.93]ANCOVA
Comparison: \>=10%p-value: 0.94395% CI: [0.1, 12.41]ANCOVA
Comparison: \>=10%p-value: 0.46595% CI: [0.28, 15.77]ANCOVA
Comparison: \>=10%p-value: 0.69695% CI: [0.15, 17.15]ANCOVA
Comparison: \>=10%p-value: 0.38995% CI: [0.38, 12.1]ANCOVA
Comparison: \>=10%p-value: 0.97695% CI: [0.09, 11.87]ANCOVA
Comparison: \>=10%p-value: 0.98695% CI: [0.09, 11.7]ANCOVA
Comparison: \>=10%p-value: 0.18195% CI: [0.56, 22.18]ANCOVA
Comparison: \>=10%p-value: 0.195% CI: [0.77, 20.54]ANCOVA
Secondary
Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups
Responder rates according to percentage decrease in body weight either ≥ 5 % or ≥ 10 % from baseline for dysglycemic, normoglycemic, Type 2 Diabetes Mellitus (T2DM)
Time frame: Baseline, Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 31.3 Percentage |
| LIK066 2.5mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 7.7 Percentage |
| LIK066 2.5mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 44.4 Percentage |
| LIK066 10mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 15.4 Percentage |
| LIK066 10mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 11.1 Percentage |
| LIK066 10mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 25.0 Percentage |
| LIK066 50mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 44.4 Percentage |
| LIK066 50mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 40.0 Percentage |
| LIK066 50mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 28.6 Percentage |
| LIK066 150mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 37.0 Percentage |
| LIK066 150mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 48.4 Percentage |
| LIK066 150mg qd (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 47.4 Percentage |
| LIK066 2.5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 11.1 Percentage |
| LIK066 2.5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 6.7 Percentage |
| LIK066 2.5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 28.6 Percentage |
| LIK066 5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 11.1 Percentage |
| LIK066 5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 37.5 Percentage |
| LIK066 5mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 14.3 Percentage |
| LIK066 25mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 30.8 Percentage |
| LIK066 25mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 40.0 Percentage |
| LIK066 25mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 55.6 Percentage |
| LIK066 50mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 52.9 Percentage |
| LIK066 50mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 44.4 Percentage |
| LIK066 50mg Bid (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 41.9 Percentage |
| Placebo (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Normoglycemic (>=5%) | 20.0 Percentage |
| Placebo (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Type 2 Diabetes Mellitus (T2DM) (>=5%) | 14.8 Percentage |
| Placebo (Epoch 3) | Number of Subjects With Response Rate According to Percent Decrease in Body Weight for Subgroups | Dysglycemic (>=5%) | 9.7 Percentage |
Comparison: \>=5% (Dysglycemic)p-value: 0.04895% CI: [1.02, 38.76]ANCOVA
Comparison: \>=5% (Dsyglycemic)p-value: 0.17195% CI: [0.55, 28.03]ANCOVA
Comparison: \>=5% (Dysglycemic)p-value: 0.04195% CI: [1.09, 47.27]ANCOVA
Comparison: \>=5% (Dysglycemic)p-value: 0.00395% CI: [2.32, 60.93]ANCOVA
Comparison: \>=5% (Dysglycemic)p-value: 0.97695% CI: [0.08, 11.72]ANCOVA
Comparison: \>=5% (Dysglycemic)p-value: 0.02295% CI: [1.37, 56.44]ANCOVA
Comparison: \>=5% (Dysglycemic)p-value: 0.03295% CI: [1.2, 46.99]ANCOVA
Comparison: \>=5% (Dysglycemic)p-value: 0.00595% CI: [2.11, 60.46]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.22795% CI: [0.48, 21.28]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.76395% CI: [0.06, 7.85]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.09595% CI: [0.76, 28.7]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.03395% CI: [1.14, 24.83]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.78895% CI: [0.06, 8.1]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.75195% CI: [0.06, 7.62]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.02795% CI: [1.27, 51.09]ANCOVA
Comparison: \>=5% (Normoglycemic)p-value: 0.02395% CI: [1.3, 34]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.52895% CI: [0.05, 4.78]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.95895% CI: [0.17, 6.68]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.54695% CI: [0.3, 9.49]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.09895% CI: [0.81, 11.75]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.56395% CI: [0.31, 8.7]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.6195% CI: [0.06, 5.38]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.52895% CI: [0.32, 9.16]ANCOVA
Comparison: \>=5% (T2DM)p-value: 0.02395% CI: [1.23, 16.9]ANCOVA
Secondary
Percentage Change From Baseline on Waist Circumference
Waist circumference will be measured to the nearest 0.1cm in a standing position, at the end of a normal expiration, using a tape at the level of the iliac crest.
Time frame: Baseline, Week 24 (Epoch 3), Week 24 to Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -2.1 Percentage Change |
| LIK066 10mg qd (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -2.7 Percentage Change |
| LIK066 50mg qd (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -3.7 Percentage Change |
| LIK066 150mg qd (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -5.6 Percentage Change |
| LIK066 2.5mg Bid (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -2.7 Percentage Change |
| LIK066 5mg Bid (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -4.3 Percentage Change |
| LIK066 25mg Bid (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -4.8 Percentage Change |
| LIK066 50mg Bid (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -4.6 Percentage Change |
| Placebo (Epoch 3) | Percentage Change From Baseline on Waist Circumference | -1.3 Percentage Change |
| LIK066 qd/LIK066 25mg qd (Epoch 4) | Percentage Change From Baseline on Waist Circumference | -0.4 Percentage Change |
| LIK066 Bid/LIK066 35mg qd (Epoch 4) | Percentage Change From Baseline on Waist Circumference | -0.7 Percentage Change |
| Placebo/LIK066 25mg qd (Epoch 4) | Percentage Change From Baseline on Waist Circumference | -2.1 Percentage Change |
| Placebo/Placebo (Epoch 4) | Percentage Change From Baseline on Waist Circumference | 0.4 Percentage Change |
p-value: 0.4795% CI: [-2.96, 1.37]ANCOVA
p-value: 0.19995% CI: [-3.64, 0.76]ANCOVA
p-value: <0.00195% CI: [-3.64, 0.76]ANCOVA
p-value: 0.20695% CI: [-3.56, 0.77]ANCOVA
p-value: 0.00695% CI: [-5.18, -0.88]ANCOVA
p-value: 0.00295% CI: [-5.7, -1.3]ANCOVA
p-value: <0.00195% CI: [-5.1, -1.51]ANCOVA
p-value: 0.39195% CI: [-2.82, 1.1]ANCOVA
p-value: 0.25995% CI: [-3.1, 0.84]ANCOVA
p-value: 0.04895% CI: [-4.91, -0.02]ANCOVA
Secondary
Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4)
Between -treatment analysis of percentage change from Week 24 in body weight (kg) at Week 48 (Epoch 4)
Time frame: Between Week 24 and Week 48 (Epoch 4)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4) | -0.2 Percentage |
| LIK066 10mg qd (Epoch 3) | Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4) | -0.2 Percentage |
| LIK066 50mg qd (Epoch 3) | Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4) | -2.4 Percentage |
| LIK066 150mg qd (Epoch 3) | Percentage Change in Weight in the Overall Population and by Subgroups (Epoch 4) | 0.4 Percentage |
p-value: 0.35595% CI: [-1.84, 0.66]ANCOVA
p-value: 0.37395% CI: [-1.83, 0.69]ANCOVA
p-value: <0.00195% CI: [-4.36, -1.24]ANCOVA
Secondary
Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t)
Area under the plasma concentration-time curve from time zero time 't' where t is a defined time point after administration (AUC0-t)
Time frame: Summary at Week 24 from qd or bid regimens (0-6h)
Population: Full Analysis Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 196 hr*ng/mL | Standard Deviation 186 |
| LIK066 10mg qd (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 275 hr*ng/mL | Standard Deviation 0 |
| LIK066 50mg qd (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 2280 hr*ng/mL | Standard Deviation 522 |
| LIK066 150mg qd (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 5700 hr*ng/mL | Standard Deviation 1490 |
| LIK066 2.5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 105 hr*ng/mL | Standard Deviation 17.1 |
| LIK066 5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 273 hr*ng/mL | Standard Deviation 69.3 |
| LIK066 25mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 1520 hr*ng/mL | Standard Deviation 277 |
| LIK066 50mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' (AUC0-t) | 2190 hr*ng/mL | Standard Deviation 841 |
Secondary
Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast)
Last non-zero concentration area under the curve (AUClast)
Time frame: Summary at Week 24 from qd or bid regimens
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 196 hr*ng/mL | Standard Deviation 186 |
| LIK066 10mg qd (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 275 hr*ng/mL | Standard Deviation 0 |
| LIK066 50mg qd (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 2290 hr*ng/mL | Standard Deviation 526 |
| LIK066 150mg qd (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 5690 hr*ng/mL | Standard Deviation 1480 |
| LIK066 2.5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 105 hr*ng/mL | Standard Deviation 17.2 |
| LIK066 5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 273 hr*ng/mL | Standard Deviation 70.2 |
| LIK066 25mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 1520 hr*ng/mL | Standard Deviation 271 |
| LIK066 50mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Last Non-zero Concentration Area Under the Curve (AUClast) | 2190 hr*ng/mL | Standard Deviation 843 |
Secondary
Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax)
Observe maximum plasma concentration following administration of LIK066 (Cmax)
Time frame: Summary at Week 24 from qd or bid regimens
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 80.0 ng/mL | Standard Deviation 97.2 |
| LIK066 10mg qd (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 128 ng/mL | Standard Deviation 0 |
| LIK066 50mg qd (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 798 ng/mL | Standard Deviation 397 |
| LIK066 150mg qd (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 1810 ng/mL | Standard Deviation 545 |
| LIK066 2.5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 38.6 ng/mL | Standard Deviation 5.22 |
| LIK066 5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 84.2 ng/mL | Standard Deviation 19 |
| LIK066 25mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 523 ng/mL | Standard Deviation 118 |
| LIK066 50mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Observe Maximum Plasma Concentration (Cmax) | 811 ng/mL | Standard Deviation 367 |
Secondary
Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax)
Time to reach the maximum concentration after administration of LIK066 (Tmax)
Time frame: Summary at Week 24 for qd or bid regimens
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LIK066 2.5mg qd (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 1.00 hour |
| LIK066 10mg qd (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 1.00 hour |
| LIK066 50mg qd (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 1.01 hour |
| LIK066 150mg qd (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 1.02 hour |
| LIK066 2.5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 1.00 hour |
| LIK066 5mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 1.00 hour |
| LIK066 25mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 0.992 hour |
| LIK066 50mg Bid (Epoch 3) | Pharmacokinetics of LIK066: Time to Reach the Maximum Concentration (Tmax) | 1.00 hour |