Trial Outcomes & Findings for Effect of LIK066 on Body Weight in Patients With Elevated Body Mass Index (NCT NCT02470403)

NCT ID: NCT02470403

Last Updated: 2021-01-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 181 participants
• Primary outcome timeframe: Baseline, Week 12 (Day 85)
• Results posted on: 2021-01-05

Participant Flow

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.

Participant milestones

Measure	Part 1: LIK066 150 mg Once Daily (qd) LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 75 mg Twice Daily (Bid) LIK066 75 mg bid before breakfast and dinner	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 2: Placebo Three Times Daily Matching placebo tablets tid before meals.
Overall Study STARTED	44	44	40	43	10
Overall Study Dysglycemic	24	24	20	20	5
Overall Study Normoglycemic	20	20	20	23	5
Overall Study COMPLETED	42	43	40	39	10
Overall Study NOT COMPLETED	2	1	0	4	0

Reasons for withdrawal

Measure	Part 1: LIK066 150 mg Once Daily (qd) LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 75 mg Twice Daily (Bid) LIK066 75 mg bid before breakfast and dinner	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 2: Placebo Three Times Daily Matching placebo tablets tid before meals.
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

Effect of LIK066 on Body Weight in Patients With Elevated Body Mass Index

Baseline characteristics by cohort

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=44 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=44 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 75 mg Twice Daily (Bid) n=40 Participants LIK066 75 mg bid before breakfast and dinner	Part 2: LIK066 50 mg Three Times Daily (Tid) n=43 Participants LIK066 50 mg tid before all 3 meals;	Part 2: Placebo Three Times Daily n=10 Participants Matching placebo tablets tid before meals.	Total n=181 Participants Total of all reporting groups
Age, Continuous Part 1 (44, 44, NA,NA,NA,88)	39.0 Years STANDARD_DEVIATION 12.01 • n=5 Participants	41.3 Years STANDARD_DEVIATION 11.07 • n=7 Participants	NA Years STANDARD_DEVIATION NA • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=4 Participants	NA Years STANDARD_DEVIATION NA • n=21 Participants	40.2 Years STANDARD_DEVIATION 11.54 • n=10 Participants
Age, Continuous Part 2 (NA, NA, 40,43,10,93)	NA Years STANDARD_DEVIATION NA • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=7 Participants	42.9 Years STANDARD_DEVIATION 8.96 • n=5 Participants	39.9 Years STANDARD_DEVIATION 11.22 • n=4 Participants	43.4 Years STANDARD_DEVIATION 12.39 • n=21 Participants	41.6 Years STANDARD_DEVIATION 10.44 • n=10 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	26 Participants n=7 Participants	26 Participants n=5 Participants	26 Participants n=4 Participants	8 Participants n=21 Participants	105 Participants n=10 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	18 Participants n=7 Participants	14 Participants n=5 Participants	17 Participants n=4 Participants	2 Participants n=21 Participants	76 Participants n=10 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=44 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=43 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
Part 1: Percent Change in Body Weight From Baseline to Week 12 All subjects (n= 42, 43)	-5.51 percent change Interval -6.09 to -4.93	0.19 percent change Interval -0.39 to 0.78	—	—
Part 1: Percent Change in Body Weight From Baseline to Week 12 Dysglycemic subjects (n= 22, 23)	-6.55 percent change Interval -7.34 to -5.77	0.29 percent change Interval -0.5 to 1.09	—	—
Part 1: Percent Change in Body Weight From Baseline to Week 12 Normoglycemic subjects (n= 20,20)	-4.46 percent change Interval -5.31 to -3.6	0.09 percent change Interval -0.77 to 0.94	—	—

PRIMARY outcome

Timeframe: 12 weeks

Population: The safety analysis set included all subjects that received any study drug.

This endpoint reports patients with at least one AE (any AE), serious AE and death.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=44 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=44 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death With at least one AE (any AE)	43 Patients	39 Patients	—	—
Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death Serious AE	1 Patients	0 Patients	—	—
Part 1: Number of Patients With Any Adverse Events, Serious Adverse Events and Death Death	0 Patients	0 Patients	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=44 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=40 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) n=39 Participants LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo n=53 Participants Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
Part 1 and Part 2: Percent Change in Body Weight From Baseline to Week 2 (Day 14)	-1.17 Percent change Interval -2.21 to -0.12	-1.73 Percent change Interval -2.75 to -0.7	-1.71 Percent change Interval -2.74 to -0.69	0.66 Percent change Interval -0.46 to 1.79

PRIMARY outcome

Timeframe: 2 weeks

Population: The safety analysis set included all subjects that received any study drug.

This endpoint reports patients with at least one AE (any AE), serious AE and death

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=43 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) n=10 Participants LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death At least one AE (Any AE)	40 Patients	43 Patients	10 Patients	—
Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death Serious AE	0 Patients	0 Patients	0 Patients	—
Part 2: Number of Patients With Any Adverse Events, Serious Adverse Events and Death Death	0 Patients	0 Patients	0 Patients	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=43 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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 Interval -2.89 to -1.09	-1.73 percent change Interval -2.62 to -0.84	—	—
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 Interval -2.36 to -0.57	-1.70 percent change Interval -2.6 to -0.8	—	—

SECONDARY outcome

Timeframe: Day 84

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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	—	—	—
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	—	—	—
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 outcome

Timeframe: Day 84

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study Dysglycemic (n=22)	3.02 hour Interval 0.517 to 4.03	—	—	—
Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study Normoglycemic (n=18)	4.02 hour Interval 0.517 to 6.0	—	—	—
Time to Maximum Plasma Concentration of LIK066 at Steady State (Tmax, ss) in Part 1 of the Study Overall (n=40)	3.02 hour Interval 0.517 to 6.0	—	—	—

SECONDARY outcome

Timeframe: Day 84

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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	—	—	—
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	—	—	—
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 outcome

Timeframe: Day 84

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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	—	—	—
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	—	—	—
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 outcome

Timeframe: Day 84

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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	—	—	—
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	—	—	—
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 outcome

Timeframe: Day 84

Population: The PK analysis set included all subjects with available PK data and no protocol deviations with relevant impact on PK data.

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.

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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	—	—	—
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	—	—	—
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 outcome

Timeframe: 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.

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)

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=39 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study Day 1, Dysglycemic (n= 19, 20)	728 ng/mL Standard Deviation 274	513 ng/mL Standard Deviation 176	—	—
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study Day 1, Normoglycemic (n= 19, 19)	767 ng/mL Standard Deviation 275	517 ng/mL Standard Deviation 223	—	—
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study Day 1, Overall (n= 38, 39)	747 ng/mL Standard Deviation 272	515 ng/mL Standard Deviation 198	—	—
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study Day 14, Dysglycemic (n= 20, 19)	1100 ng/mL Standard Deviation 361	716 ng/mL Standard Deviation 282	—	—
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study Day 14, Normoglycemic (n= 20, 19)	1030 ng/mL Standard Deviation 266	792 ng/mL Standard Deviation 276	—	—
Maximum Plasma Concentration of LIK066 (Cmax) in Part 2 of the Study Day 14, Overall (n= 40, 38)	1070 ng/mL Standard Deviation 315	754 ng/mL Standard Deviation 278	—	—

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=39 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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 • Interval 0.483 to 4.53	1.00 hour Full Range 176 • Interval 0.483 to 3.98	—	—
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 • Interval 0.483 to 6.0	0.983 hour Full Range 223 • Interval 0.483 to 2.0	—	—
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 • Interval 0.483 to 6.0	1.00 hour Full Range 198 • Interval 0.483 to 3.98	—	—
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 • Interval 0.483 to 4.5	1.00 hour Full Range 282 • Interval 0.5 to 3.9	—	—
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 • Interval 0.483 to 3.0	0.533 hour Full Range 276 • Interval 0.5 to 3.92	—	—
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 • Interval 0.483 to 4.5	1.00 hour Full Range 278 • Interval 0.5 to 3.92	—	—

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=39 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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	3910 hr*ng/mL Standard Deviation 840	—	—
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	3870 hr*ng/mL Standard Deviation 1360	—	—
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	3890 hr*ng/mL Standard Deviation 1110	—	—
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	4740 hr*ng/mL Standard Deviation 1200	—	—
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	4950 hr*ng/mL Standard Deviation 1580	—	—
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	4850 hr*ng/mL Standard Deviation 1390	—	—

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=39 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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	1340 hr*ng/mL Standard Deviation 295	—	—
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	1350 hr*ng/mL Standard Deviation 429	—	—
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	1350 hr*ng/mL Standard Deviation 362	—	—
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	1940 hr*ng/mL Standard Deviation 600	—	—
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	2000 hr*ng/mL Standard Deviation 586	—	—
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	1970 hr*ng/mL Standard Deviation 586	—	—

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=39 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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 • Interval 0.483 to 4.53	39.3 Liter/hour Standard Deviation 9.42 • Interval 0.483 to 3.98	—	—
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 • Interval 0.483 to 6.0	40.5 Liter/hour Standard Deviation 12.8 • Interval 0.483 to 2.0	—	—
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 • Interval 0.483 to 6.0	39.9 Liter/hour Standard Deviation 11.1 • Interval 0.483 to 3.98	—	—
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 • Interval 0.483 to 4.5	27.8 Liter/hour Standard Deviation 7.35 • Interval 0.5 to 3.9	—	—
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 • Interval 0.483 to 3.0	27.2 Liter/hour Standard Deviation 8.50 • Interval 0.5 to 3.92	—	—
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 4.40 • Interval 0.483 to 4.5	27.5 Liter/hour Standard Deviation 7.84 • Interval 0.5 to 3.92	—	—

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=40 Participants LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=39 Participants Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 50 mg Three Times Daily (Tid) LIK066 50 mg tid before all 3 meals;	Part 1 and 2 : Pooled Placebo Placebo subjects were pooled between the 2 parts and were considered a single treatment arm for the analyses
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 • Interval 0.483 to 3.0	267 Liter Standard Deviation 493 • Interval 0.5 to 3.92	—	—
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 • Interval 0.483 to 4.53	274 Liter Standard Deviation 224 • Interval 0.483 to 3.98	—	—
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 • Interval 0.483 to 6.0	519 Liter Standard Deviation 1330 • Interval 0.483 to 2.0	—	—
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 • Interval 0.483 to 6.0	390 Liter Standard Deviation 919 • Interval 0.483 to 3.98	—	—
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 • Interval 0.483 to 4.5	580 Liter Standard Deviation 1380 • Interval 0.5 to 3.9	—	—
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 • Interval 0.483 to 4.5	410 Liter Standard Deviation 997 • Interval 0.5 to 3.92	—	—

Adverse Events

Part 1: LIK066 150 mg Once Daily (qd)

Serious events: 1 serious events

Other events: 43 other events

Deaths: 0 deaths

Part 1: Placebo Once Daily

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Part 2: LIK066 75 mg Twice Daily (Bid)

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Part 2: LIK066 50 mg Three Times Daily (Tid)

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Part 2: Placebo Three Times Daily

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=44 participants at risk LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=44 participants at risk Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 75 mg Twice Daily (Bid) n=40 participants at risk LIK066 75 mg bid before breakfast and dinner	Part 2: LIK066 50 mg Three Times Daily (Tid) n=43 participants at risk LIK066 50 mg tid before all 3 meals;	Part 2: Placebo Three Times Daily n=10 participants at risk Matching placebo tablets tid before meals.
Infections and infestations Appendicitis perforated	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10

Other adverse events

Measure	Part 1: LIK066 150 mg Once Daily (qd) n=44 participants at risk LIK066 150 mg qd within 15 minutes before starting lunch	Part 1: Placebo Once Daily n=44 participants at risk Matching placebo tablets of LIK066 150 mg within 15 minutes before starting lunch.	Part 2: LIK066 75 mg Twice Daily (Bid) n=40 participants at risk LIK066 75 mg bid before breakfast and dinner	Part 2: LIK066 50 mg Three Times Daily (Tid) n=43 participants at risk LIK066 50 mg tid before all 3 meals;	Part 2: Placebo Three Times Daily n=10 participants at risk Matching placebo tablets tid before meals.
Ear and labyrinth disorders Ear pain	0.00% 0/44	2.3% 1/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Eye disorders Visual impairment	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Gastrointestinal disorders Abdominal discomfort	4.5% 2/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Gastrointestinal disorders Abdominal distension	25.0% 11/44	9.1% 4/44	22.5% 9/40	20.9% 9/43	0.00% 0/10
Gastrointestinal disorders Abdominal pain	27.3% 12/44	11.4% 5/44	12.5% 5/40	18.6% 8/43	0.00% 0/10
Gastrointestinal disorders Abdominal pain lower	6.8% 3/44	0.00% 0/44	2.5% 1/40	2.3% 1/43	0.00% 0/10
Gastrointestinal disorders Abdominal pain upper	2.3% 1/44	2.3% 1/44	5.0% 2/40	4.7% 2/43	0.00% 0/10
Gastrointestinal disorders Abdominal tenderness	2.3% 1/44	0.00% 0/44	0.00% 0/40	4.7% 2/43	0.00% 0/10
Gastrointestinal disorders Abnormal faeces	0.00% 0/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	10.0% 1/10
Gastrointestinal disorders Anal haemorrhage	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Gastrointestinal disorders Anorectal discomfort	2.3% 1/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Gastrointestinal disorders Constipation	2.3% 1/44	4.5% 2/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Gastrointestinal disorders Diarrhoea	90.9% 40/44	25.0% 11/44	100.0% 40/40	97.7% 42/43	80.0% 8/10
Gastrointestinal disorders Dry mouth	2.3% 1/44	2.3% 1/44	5.0% 2/40	0.00% 0/43	0.00% 0/10
Gastrointestinal disorders Dyspepsia	13.6% 6/44	9.1% 4/44	10.0% 4/40	9.3% 4/43	0.00% 0/10
Gastrointestinal disorders Eructation	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Gastrointestinal disorders Faeces hard	0.00% 0/44	0.00% 0/44	25.0% 10/40	18.6% 8/43	60.0% 6/10
Gastrointestinal disorders Flatulence	43.2% 19/44	9.1% 4/44	22.5% 9/40	27.9% 12/43	0.00% 0/10
Gastrointestinal disorders Gastrointestinal sounds abnormal	0.00% 0/44	0.00% 0/44	10.0% 4/40	2.3% 1/43	0.00% 0/10
Gastrointestinal disorders Haematochezia	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Gastrointestinal disorders Nausea	18.2% 8/44	6.8% 3/44	12.5% 5/40	18.6% 8/43	0.00% 0/10
Gastrointestinal disorders Palatal disorder	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Gastrointestinal disorders Proctalgia	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Gastrointestinal disorders Toothache	0.00% 0/44	4.5% 2/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Gastrointestinal disorders Vomiting	6.8% 3/44	6.8% 3/44	15.0% 6/40	9.3% 4/43	10.0% 1/10
General disorders Asthenia	2.3% 1/44	0.00% 0/44	2.5% 1/40	4.7% 2/43	0.00% 0/10
General disorders Chills	0.00% 0/44	0.00% 0/44	5.0% 2/40	2.3% 1/43	0.00% 0/10
General disorders Energy increased	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
General disorders Fatigue	0.00% 0/44	0.00% 0/44	5.0% 2/40	9.3% 4/43	0.00% 0/10
General disorders Feeling hot	4.5% 2/44	2.3% 1/44	2.5% 1/40	4.7% 2/43	0.00% 0/10
General disorders Feeling jittery	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
General disorders Local swelling	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
General disorders Medical device site dermatitis	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
General disorders Oedema peripheral	0.00% 0/44	4.5% 2/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
General disorders Pain	0.00% 0/44	2.3% 1/44	2.5% 1/40	2.3% 1/43	0.00% 0/10
General disorders Pyrexia	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	10.0% 1/10
General disorders Thirst	2.3% 1/44	0.00% 0/44	2.5% 1/40	2.3% 1/43	0.00% 0/10
Infections and infestations Bacterial vaginosis	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Infections and infestations Parotitis	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Infections and infestations Sinusitis	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Infections and infestations Trichomoniasis	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Infections and infestations Urinary tract infection	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Infections and infestations Vulvovaginal candidiasis	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Infections and infestations Vulvovaginal mycotic infection	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Injury, poisoning and procedural complications Animal scratch	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Injury, poisoning and procedural complications Fall	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Injury, poisoning and procedural complications Laceration	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	10.0% 1/10
Injury, poisoning and procedural complications Mouth injury	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Injury, poisoning and procedural complications Skin abrasion	4.5% 2/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Injury, poisoning and procedural complications Wrist fracture	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Investigations Blood pressure increased	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Investigations Blood triglycerides increased	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Investigations Blood urine present	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Investigations Fungal test positive	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Investigations Heart rate increased	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Metabolism and nutrition disorders Decreased appetite	6.8% 3/44	2.3% 1/44	7.5% 3/40	14.0% 6/43	0.00% 0/10
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Metabolism and nutrition disorders Increased appetite	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/44	4.5% 2/44	0.00% 0/40	0.00% 0/43	10.0% 1/10
Musculoskeletal and connective tissue disorders Back pain	4.5% 2/44	4.5% 2/44	0.00% 0/40	7.0% 3/43	0.00% 0/10
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/44	2.3% 1/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Musculoskeletal and connective tissue disorders Myalgia	4.5% 2/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/44	2.3% 1/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Nervous system disorders Burning sensation	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Nervous system disorders Dizziness	2.3% 1/44	2.3% 1/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Nervous system disorders Dizziness postural	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Nervous system disorders Dysgeusia	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Nervous system disorders Headache	20.5% 9/44	36.4% 16/44	32.5% 13/40	23.3% 10/43	20.0% 2/10
Nervous system disorders Hypoaesthesia	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Nervous system disorders Hypogeusia	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Nervous system disorders Migraine	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Nervous system disorders Presyncope	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Nervous system disorders Sinus headache	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Nervous system disorders Somnolence	2.3% 1/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Psychiatric disorders Anxiety	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Psychiatric disorders Insomnia	0.00% 0/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	20.0% 2/10
Renal and urinary disorders Dysuria	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Renal and urinary disorders Nephrolithiasis	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Renal and urinary disorders Pollakiuria	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Reproductive system and breast disorders Metrorrhagia	0.00% 0/44	0.00% 0/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Reproductive system and breast disorders Vaginal discharge	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Reproductive system and breast disorders Vulvovaginal pruritus	2.3% 1/44	0.00% 0/44	2.5% 1/40	2.3% 1/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Cough	4.5% 2/44	11.4% 5/44	10.0% 4/40	2.3% 1/43	20.0% 2/10
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/44	6.8% 3/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.8% 3/44	13.6% 6/44	5.0% 2/40	2.3% 1/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Productive cough	2.3% 1/44	4.5% 2/44	0.00% 0/40	4.7% 2/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	4.5% 2/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.3% 1/44	4.5% 2/44	7.5% 3/40	4.7% 2/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Sinus congestion	6.8% 3/44	4.5% 2/44	2.5% 1/40	2.3% 1/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Skin and subcutaneous tissue disorders Cold sweat	2.3% 1/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	10.0% 1/10
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/44	2.3% 1/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Skin and subcutaneous tissue disorders Erythema	2.3% 1/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	0.00% 0/10
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Skin and subcutaneous tissue disorders Pruritus	4.5% 2/44	0.00% 0/44	2.5% 1/40	2.3% 1/43	10.0% 1/10
Skin and subcutaneous tissue disorders Rash	0.00% 0/44	2.3% 1/44	2.5% 1/40	0.00% 0/43	0.00% 0/10
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/44	0.00% 0/44	0.00% 0/40	4.7% 2/43	0.00% 0/10
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/44	0.00% 0/44	0.00% 0/40	0.00% 0/43	10.0% 1/10
Vascular disorders Hot flush	2.3% 1/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10
Vascular disorders Hypertension	0.00% 0/44	0.00% 0/44	0.00% 0/40	2.3% 1/43	0.00% 0/10

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: trialandresults.registries@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER