Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH (NCT NCT02913105)

Last Updated: 2021-01-05

Results Overview

An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment. No statistical analysis was planned for this primary outcome measure.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

122 participants

Primary outcome timeframe

From date of First Participant First Treatment until Last Patient Last Visit (up to Day 112 (End of Study (EOS))

Results posted on

2021-01-05

Participant Flow

The study was conducted in 25 centers across 6 countries.

A total of 121 participants were enrolled in the study, and included in the safety population. Placebo data have been pooled from placebo treated participants from both cohorts (100 mg and 50 mg matching placebo).

Participant milestones

Participant milestones
Measure	LMB763 100 mg LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Overall Study STARTED	37	44	40
Overall Study COMPLETED	22	39	33
Overall Study NOT COMPLETED	15	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	LMB763 100 mg LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Overall Study Adverse Event	11	0	4
Overall Study Non-Compliance With Study Drug	0	0	1
Overall Study Reason Not Specified	3	1	1
Overall Study Physician Decision	1	1	0
Overall Study Withdrawal by Subject	0	3	1

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With NASH

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Total n=121 Participants Total of all reporting groups
Age, Continuous	51.3 years STANDARD_DEVIATION 15.55 • n=5 Participants	49.5 years STANDARD_DEVIATION 8.45 • n=7 Participants	51.6 years STANDARD_DEVIATION 11.65 • n=5 Participants	50.8 years STANDARD_DEVIATION 11.96 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	23 Participants n=7 Participants	24 Participants n=5 Participants	69 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	21 Participants n=7 Participants	16 Participants n=5 Participants	52 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	33 Participants n=7 Participants	28 Participants n=5 Participants	88 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Black Or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	32 Participants n=5 Participants	37 Participants n=7 Participants	31 Participants n=5 Participants	100 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: From date of First Participant First Treatment until Last Patient Last Visit (up to Day 112 (End of Study (EOS))

Population: Safety analysis set included all participants that received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	35 Participants	37 Participants	33 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	2 Participants	3 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline to Day 84 (Week 12)

Population: Pharmacodynamic (PD) analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data. Number analyzed included participants with a value at both Baseline and that time point.

ALT level assessment is one of the diagnostic parameters in Liver function test (LFT). Baseline was defined as the mean of ALT levels at baseline and pre-dose visits. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Alanine Aminotransferase (ALT) Levels Baseline for Day 84 Analysis	67.215 units per liter (U/L) Geometric Coefficient of Variation 30.8	48.114 units per liter (U/L) Geometric Coefficient of Variation 42.2	59.544 units per liter (U/L) Geometric Coefficient of Variation 39.5
Change From Baseline in Alanine Aminotransferase (ALT) Levels Change from Baseline at Day 84	0.667 units per liter (U/L) Geometric Coefficient of Variation 33.8	0.702 units per liter (U/L) Geometric Coefficient of Variation 41.1	0.901 units per liter (U/L) Geometric Coefficient of Variation 25.5

SECONDARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 42

Population: Pharmacokinetic (PK) analysis set included all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and with no protocol deviations that impact on PK data. Number analyzed is the number of participants with data available for analysis at specified time-point.

No statistical analysis was planned for this outcome measure.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=43 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Observed Maximum Plasma Concentration (Cmax) of LMB763 Day 1	3080 nanograms per milliliter (ng/mL) Standard Deviation 1360	1290 nanograms per milliliter (ng/mL) Standard Deviation 620	—
Observed Maximum Plasma Concentration (Cmax) of LMB763 Day 42	2230 nanograms per milliliter (ng/mL) Standard Deviation 1190	1290 nanograms per milliliter (ng/mL) Standard Deviation 690	—

SECONDARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 42

Population: PK analysis set included all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and with no protocol deviations that impact on PK data. Number analyzed is the number of participants with data available for analysis at specified time-point.

No statistical analysis was planned for this outcome measure.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=43 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Time to Reach Maximum Concentration (Tmax) of LMB763 Day 1	2.00 hour (h) Interval 1.0 to 6.0	2.00 hour (h) Interval 1.0 to 6.08	—
Time to Reach Maximum Concentration (Tmax) of LMB763 Day 42	2.03 hour (h) Interval 1.0 to 6.03	2.02 hour (h) Interval 1.0 to 6.0	—

SECONDARY outcome

Timeframe: 0 to 96 hours post-dose on Days 1 and 42

No statistical analysis was planned for this outcome measure.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=43 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of LMB763 Day 1	11200 h*ng/mL Standard Deviation 4740	4360 h*ng/mL Standard Deviation 2350	—
Area Under Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of LMB763 Day 42	8570 h*ng/mL Standard Deviation 4120	5180 h*ng/mL Standard Deviation 2870	—

SECONDARY outcome

Timeframe: Day 42

The drug accumulation ratio (Racc) is the ratio of accumulation of drug going from a single dose to steady state with repeated administration. No statistical analysis was planned for this outcome measure.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=24 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=42 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Accumulation Ratio (Racc) of LMB763	0.903 ratio Standard Deviation 0.472	1.31 ratio Standard Deviation 0.641	—

SECONDARY outcome

Timeframe: Baseline to Day 84 (Week 12)

Population: PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data. Number analyzed included participants with a value at both Baseline and that time point.

Participants were to undergo MRI twice (Baseline and End of Treatment) during the course of the study to quantitate liver fat. Baseline was defined as the last available measurement prior to the first dose. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=35 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=39 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Percentage of Liver Fat as Measured by Magnetic Resonance Imaging (MRI) Baseline for Day 84 Analysis	18.751 percentage of liver fat Geometric Coefficient of Variation 37.4	17.715 percentage of liver fat Geometric Coefficient of Variation 42.6	17.476 percentage of liver fat Geometric Coefficient of Variation 73.9
Change From Baseline in Percentage of Liver Fat as Measured by Magnetic Resonance Imaging (MRI) Change from Baseline at Day 84	0.648 percentage of liver fat Geometric Coefficient of Variation 29.3	0.681 percentage of liver fat Geometric Coefficient of Variation 38.6	0.962 percentage of liver fat Geometric Coefficient of Variation 22.2

SECONDARY outcome

Timeframe: Baseline to Days 28, 42, 56, 84 and 112 (EOS)

Baseline was defined as the last available measurement prior to the first dose.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Weight Baseline for Day 42 Analysis	96.89 kilogram (kg) Standard Deviation 22.135	97.82 kilogram (kg) Standard Deviation 17.829	95.30 kilogram (kg) Standard Deviation 23.465
Change From Baseline in Weight Change from Baseline at Day 42	-1.04 kilogram (kg) Standard Deviation 1.683	-1.08 kilogram (kg) Standard Deviation 2.335	-0.24 kilogram (kg) Standard Deviation 1.677
Change From Baseline in Weight Baseline for Day 56 Analysis	97.07 kilogram (kg) Standard Deviation 22.555	97.86 kilogram (kg) Standard Deviation 18.043	95.71 kilogram (kg) Standard Deviation 23.244
Change From Baseline in Weight Change from Baseline at Day 56	-1.39 kilogram (kg) Standard Deviation 1.970	-1.39 kilogram (kg) Standard Deviation 2.188	-0.26 kilogram (kg) Standard Deviation 1.777
Change From Baseline in Weight Baseline for Day 84 Analysis	97.34 kilogram (kg) Standard Deviation 23.370	97.11 kilogram (kg) Standard Deviation 17.905	95.91 kilogram (kg) Standard Deviation 23.563
Change From Baseline in Weight Baseline for Day 28 Analysis	99.07 kilogram (kg) Standard Deviation 22.560	97.82 kilogram (kg) Standard Deviation 17.829	95.47 kilogram (kg) Standard Deviation 22.921
Change From Baseline in Weight Change from Baseline at Day 28	-0.78 kilogram (kg) Standard Deviation 1.591	-0.71 kilogram (kg) Standard Deviation 1.725	-0.17 kilogram (kg) Standard Deviation 1.516
Change From Baseline in Weight Change from Baseline at Day 84	-1.47 kilogram (kg) Standard Deviation 2.169	-2.02 kilogram (kg) Standard Deviation 3.451	-0.21 kilogram (kg) Standard Deviation 1.989
Change From Baseline in Weight Baseline for Day 112 (EOS) Analysis	98.74 kilogram (kg) Standard Deviation 23.941	95.38 kilogram (kg) Standard Deviation 14.810	95.85 kilogram (kg) Standard Deviation 23.926
Change From Baseline in Weight Change from Baseline at Day 112 (EOS)	-1.26 kilogram (kg) Standard Deviation 3.014	-1.66 kilogram (kg) Standard Deviation 3.543	0.35 kilogram (kg) Standard Deviation 2.125

SECONDARY outcome

Timeframe: Baseline to Days 28, 42, 56, 84 and 112 (EOS)

Baseline was defined as the last available measurement prior to the first dose at specified visit (day).

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Body Mass Index (BMI) Baseline for Day 84 Analysis	34.18 kilograms per meter square (kg/m^2) Standard Deviation 5.467	34.04 kilograms per meter square (kg/m^2) Standard Deviation 5.190	34.89 kilograms per meter square (kg/m^2) Standard Deviation 5.275
Change From Baseline in Body Mass Index (BMI) Change from Baseline at Day 84	-0.52 kilograms per meter square (kg/m^2) Standard Deviation 0.764	-0.72 kilograms per meter square (kg/m^2) Standard Deviation 1.215	-0.09 kilograms per meter square (kg/m^2) Standard Deviation 0.718
Change From Baseline in Body Mass Index (BMI) Baseline for Day 28 Analysis	34.81 kilograms per meter square (kg/m^2) Standard Deviation 5.641	34.41 kilograms per meter square (kg/m^2) Standard Deviation 5.270	34.93 kilograms per meter square (kg/m^2) Standard Deviation 5.180
Change From Baseline in Body Mass Index (BMI) Change from Baseline at Day 28	-0.29 kilograms per meter square (kg/m^2) Standard Deviation 0.545	-0.26 kilograms per meter square (kg/m^2) Standard Deviation 0.638	-0.05 kilograms per meter square (kg/m^2) Standard Deviation 0.511
Change From Baseline in Body Mass Index (BMI) Baseline for Day 42 Analysis	34.05 kilograms per meter square (kg/m^2) Standard Deviation 5.162	34.41 kilograms per meter square (kg/m^2) Standard Deviation 5.270	34.56 kilograms per meter square (kg/m^2) Standard Deviation 5.233
Change From Baseline in Body Mass Index (BMI) Change from Baseline at Day 42	-0.36 kilograms per meter square (kg/m^2) Standard Deviation 0.591	-0.40 kilograms per meter square (kg/m^2) Standard Deviation 0.845	-0.08 kilograms per meter square (kg/m^2) Standard Deviation 0.572
Change From Baseline in Body Mass Index (BMI) Baseline for Day 56 Analysis	34.12 kilograms per meter square (kg/m^2) Standard Deviation 5.253	34.37 kilograms per meter square (kg/m^2) Standard Deviation 5.327	34.75 kilograms per meter square (kg/m^2) Standard Deviation 5.269
Change From Baseline in Body Mass Index (BMI) Change from Baseline at Day 56	-0.50 kilograms per meter square (kg/m^2) Standard Deviation 0.688	-0.49 kilograms per meter square (kg/m^2) Standard Deviation 0.799	-0.10 kilograms per meter square (kg/m^2) Standard Deviation 0.663
Change From Baseline in Body Mass Index (BMI) Baseline for Day 112 (EOS) Analysis	34.60 kilograms per meter square (kg/m^2) Standard Deviation 5.522	33.82 kilograms per meter square (kg/m^2) Standard Deviation 4.980	34.96 kilograms per meter square (kg/m^2) Standard Deviation 5.342
Change From Baseline in Body Mass Index (BMI) Change from Baseline at Day 112 (EOS)	-0.45 kilograms per meter square (kg/m^2) Standard Deviation 0.974	-0.60 kilograms per meter square (kg/m^2) Standard Deviation 1.276	0.12 kilograms per meter square (kg/m^2) Standard Deviation 0.776

SECONDARY outcome

Timeframe: Baseline to Days 28, 42, 56, 84 and 112 (EOS)

Baseline was defined as the last available measurement prior to the first dose.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Waist to Hip Ratio Baseline for Day 28 Analysis	0.96 ratio Standard Deviation 0.065	0.96 ratio Standard Deviation 0.055	0.95 ratio Standard Deviation 0.089
Change From Baseline in Waist to Hip Ratio Change from Baseline at Day 28	0.00 ratio Standard Deviation 0.039	0.00 ratio Standard Deviation 0.034	-0.00 ratio Standard Deviation 0.039
Change From Baseline in Waist to Hip Ratio Baseline for Day 42 Analysis	0.96 ratio Standard Deviation 0.061	0.95 ratio Standard Deviation 0.056	0.96 ratio Standard Deviation 0.086
Change From Baseline in Waist to Hip Ratio Change from Baseline at Day 42	0.01 ratio Standard Deviation 0.077	-0.00 ratio Standard Deviation 0.039	0.00 ratio Standard Deviation 0.036
Change From Baseline in Waist to Hip Ratio Baseline for Day 56 Analysis	0.96 ratio Standard Deviation 0.061	0.96 ratio Standard Deviation 0.054	0.96 ratio Standard Deviation 0.087
Change From Baseline in Waist to Hip Ratio Change from Baseline at Day 56	-0.00 ratio Standard Deviation 0.029	-0.00 ratio Standard Deviation 0.033	-0.01 ratio Standard Deviation 0.029
Change From Baseline in Waist to Hip Ratio Baseline for Day 84 Analysis	0.95 ratio Standard Deviation 0.063	0.96 ratio Standard Deviation 0.055	0.96 ratio Standard Deviation 0.087
Change From Baseline in Waist to Hip Ratio Change from Baseline at Day 84	0.00 ratio Standard Deviation 0.043	-0.01 ratio Standard Deviation 0.044	0.01 ratio Standard Deviation 0.046
Change From Baseline in Waist to Hip Ratio Baseline for Day 112 (EOS) Analysis	0.96 ratio Standard Deviation 0.059	0.96 ratio Standard Deviation 0.054	0.96 ratio Standard Deviation 0.087
Change From Baseline in Waist to Hip Ratio Change from Baseline at Day 112 (EOS)	-0.00 ratio Standard Deviation 0.030	0.00 ratio Standard Deviation 0.050	-0.00 ratio Standard Deviation 0.037

SECONDARY outcome

Timeframe: Baseline to Day 84 (Week 12)

Fibroscan® was performed where available to assess liver stiffness. Baseline was defined as the last available measurement prior to the first dose. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=10 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=17 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=18 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From to Baseline in Liver Stiffness Change from Baseline at Day 84	0.955 kilopascal (kPa) Geometric Coefficient of Variation 35.3	1.053 kilopascal (kPa) Geometric Coefficient of Variation 26.9	1.041 kilopascal (kPa) Geometric Coefficient of Variation 38.6
Change From to Baseline in Liver Stiffness Baseline for Day 84 Analysis	7.689 kilopascal (kPa) Geometric Coefficient of Variation 71.1	6.082 kilopascal (kPa) Geometric Coefficient of Variation 29.5	7.108 kilopascal (kPa) Geometric Coefficient of Variation 52.5

SECONDARY outcome

Timeframe: Baseline to Days 42 and 84

The ADVIA CentaurR systems' ELF™ test is an in vitro diagnostic multivariate index assay that provides a single score by combining quantitative measurements of hyaluronic acid (HA), amino-terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human serum using the ADVIA Centaur XP, ADVIA Centaur XPT, and ADVIA Centaur CP systems in an algorithm. ELF score for the ADVIA Centaur systems is calculated by, first obtaining results for the ADVIA Centaur HA, PIIINP, and TIMP-1 assays and then using the following equation/algorithm: ADVIA Centaur XP/XPT: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln(CP3NP) + 0.394 ln(CTIMP1) ADVIA Centaur CP: ELF score = 2.494 + 0.846 ln(CHA) + 0.735 ln(CP3NP) + 0.391 ln(CTIMP1) Concentrations (C) of each assay are in ng/mL Interpretation of ELF score is as follows: \< 7.7 None to mild * 7.7 to \< 9.8 Moderate * 9.8 Severe

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Enhanced Liver Fibrosis (ELF) Test Panel Change from Baseline at Day 42	1.005 ELF score Geometric Coefficient of Variation 5.5	1.016 ELF score Geometric Coefficient of Variation 5.8	1.009 ELF score Geometric Coefficient of Variation 7.5
Change From Baseline in Enhanced Liver Fibrosis (ELF) Test Panel Baseline for Day 84 Analysis	9.051 ELF score Geometric Coefficient of Variation 7.7	8.739 ELF score Geometric Coefficient of Variation 8.4	9.220 ELF score Geometric Coefficient of Variation 7.8
Change From Baseline in Enhanced Liver Fibrosis (ELF) Test Panel Baseline for Day 42 Analysis	9.063 ELF score Geometric Coefficient of Variation 7.3	8.731 ELF score Geometric Coefficient of Variation 8.2	9.212 ELF score Geometric Coefficient of Variation 8.0
Change From Baseline in Enhanced Liver Fibrosis (ELF) Test Panel Change from Baseline at Day 84	1.005 ELF score Geometric Coefficient of Variation 5.9	1.030 ELF score Geometric Coefficient of Variation 6.2	1.007 ELF score Geometric Coefficient of Variation 6.3

SECONDARY outcome

Timeframe: Baseline to Days 42 and 84

Population: PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data. Number analyzed in the number of participants with all observations non-missing, including censored data.

Fibrosis Biomarker test included hyaluronic acid (HA), amino-terminal pro-peptide of procollagen type III (PIIINP), and tissue inhibitor of metalloproteinases (TIMP-1) as markers of liver fibrosis. Baseline was defined as the last available measurement prior to the first dose. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Fibrosis Biomarker Test HA: Baseline for Day 42 Analysis	33.646 micrograms per liter (ug/L) Geometric Coefficient of Variation 72.2	26.869 micrograms per liter (ug/L) Geometric Coefficient of Variation 75.4	39.282 micrograms per liter (ug/L) Geometric Coefficient of Variation 74.9
Change From Baseline in Fibrosis Biomarker Test HA: Change from Baseline at Day 42	1.002 micrograms per liter (ug/L) Geometric Coefficient of Variation 49.5	1.133 micrograms per liter (ug/L) Geometric Coefficient of Variation 54.4	1.111 micrograms per liter (ug/L) Geometric Coefficient of Variation 77.0
Change From Baseline in Fibrosis Biomarker Test HA: Change from Baseline at Day 84	1.023 micrograms per liter (ug/L) Geometric Coefficient of Variation 54.0	1.254 micrograms per liter (ug/L) Geometric Coefficient of Variation 51.4	1.071 micrograms per liter (ug/L) Geometric Coefficient of Variation 64.9
Change From Baseline in Fibrosis Biomarker Test PIIINP: Baseline for Day 42 Analysis	9.023 micrograms per liter (ug/L) Geometric Coefficient of Variation 31.3	7.850 micrograms per liter (ug/L) Geometric Coefficient of Variation 28.2	9.087 micrograms per liter (ug/L) Geometric Coefficient of Variation 35.5
Change From Baseline in Fibrosis Biomarker Test PIIINP: Baseline for Day 84 Analysis	9.263 micrograms per liter (ug/L) Geometric Coefficient of Variation 34.6	7.859 micrograms per liter (ug/L) Geometric Coefficient of Variation 27.4	8.934 micrograms per liter (ug/L) Geometric Coefficient of Variation 32.3
Change From Baseline in Fibrosis Biomarker Test HA: Baseline for Day 84 Analysis	32.246 micrograms per liter (ug/L) Geometric Coefficient of Variation 72.9	27.320 micrograms per liter (ug/L) Geometric Coefficient of Variation 78.2	40.865 micrograms per liter (ug/L) Geometric Coefficient of Variation 79.5
Change From Baseline in Fibrosis Biomarker Test PIIINP: Change from Baseline at Day 42	1.016 micrograms per liter (ug/L) Geometric Coefficient of Variation 22.8	1.071 micrograms per liter (ug/L) Geometric Coefficient of Variation 24.3	1.010 micrograms per liter (ug/L) Geometric Coefficient of Variation 26.4
Change From Baseline in Fibrosis Biomarker Test PIIINP: Change from Baseline at Day 84	1.003 micrograms per liter (ug/L) Geometric Coefficient of Variation 21.2	1.048 micrograms per liter (ug/L) Geometric Coefficient of Variation 26.9	1.004 micrograms per liter (ug/L) Geometric Coefficient of Variation 20.1
Change From Baseline in Fibrosis Biomarker Test TIMP-1: Baseline for Day 42 Analysis	242.99 micrograms per liter (ug/L) Geometric Coefficient of Variation 17.5	199.21 micrograms per liter (ug/L) Geometric Coefficient of Variation 78.4	254.37 micrograms per liter (ug/L) Geometric Coefficient of Variation 23.1
Change From Baseline in Fibrosis Biomarker Test TIMP-1: Change from Baseline at Day 42	1.060 micrograms per liter (ug/L) Geometric Coefficient of Variation 14.6	1.017 micrograms per liter (ug/L) Geometric Coefficient of Variation 11.9	0.995 micrograms per liter (ug/L) Geometric Coefficient of Variation 13.3
Change From Baseline in Fibrosis Biomarker Test TIMP-1: Baseline for Day 84 Analysis	247.42 micrograms per liter (ug/L) Geometric Coefficient of Variation 18.8	193.32 micrograms per liter (ug/L) Geometric Coefficient of Variation 83.6	245.09 micrograms per liter (ug/L) Geometric Coefficient of Variation 20.5
Change From Baseline in Fibrosis Biomarker Test TIMP-1: Change from Baseline at Day 84	1.073 micrograms per liter (ug/L) Geometric Coefficient of Variation 17.0	1.036 micrograms per liter (ug/L) Geometric Coefficient of Variation 10.4	1.000 micrograms per liter (ug/L) Geometric Coefficient of Variation 19.2

SECONDARY outcome

Timeframe: Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS)

Lipid measurements were collected under fasted conditions. Baseline was defined as the last available measurement prior to the first dose. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).

Outcome measures

SECONDARY outcome

Timeframe: Baseline to Days 7, 14, 28, 42, 56, 84 and 112 (EOS)

Baseline was defined as the last available measurement prior to the first dose. Geometric Mean and Geometric Coefficient of Variation for change are based on log-transformed ratio to baseline (i.e., change from baseline in the log domain).

Outcome measures

SECONDARY outcome

Timeframe: Baseline to Day 84 (Week 12)

A 10 cm VAS was used to assess the severity of participants itch (ranging from 0 = no itch at all to 10 = the worst imaginable itch). The score (distance from left) on the VAS was recorded by the participant marking with a line and used to test for an effect of LMB763 over placebo. Baseline was defined as the last available measurement prior to the first dose. A positive change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Visual Analog Scale (VAS) for Itching of Skin Baseline for Day 84 Analysis	8.87 score on a scale Standard Deviation 19.108	4.62 score on a scale Standard Deviation 10.356	9.68 score on a scale Standard Deviation 19.552
Change From Baseline in Visual Analog Scale (VAS) for Itching of Skin Change from Baseline at Day 84	9.35 score on a scale Standard Deviation 18.746	4.85 score on a scale Standard Deviation 21.798	2.03 score on a scale Standard Deviation 24.037

Adverse Events

LMB763 100 mg

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

LMB763 50 mg

Serious events: 3 serious events

Other events: 37 other events

Deaths: 0 deaths

Pooled Placebo

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LMB763 100 mg n=37 participants at risk LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 participants at risk LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 participants at risk LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Hepatobiliary disorders Cholelithiasis	0.00% 0/37 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	2.3% 1/44 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	0.00% 0/40 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))
Hepatobiliary disorders Jaundice cholestatic	2.7% 1/37 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	0.00% 0/44 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	0.00% 0/40 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))
Infections and infestations Otitis media	0.00% 0/37 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	2.3% 1/44 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	0.00% 0/40 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign small intestinal neoplasm	2.7% 1/37 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	0.00% 0/44 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	0.00% 0/40 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/37 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	2.3% 1/44 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))	0.00% 0/40 • Adverse events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until LPLV (up to Day 112 (EOS))

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Baseline for Day 14 Analysis	186.57 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 23.1	183.30 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.1	188.97 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.0
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Baseline for Day 28 Analysis	188.09 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 23.2	183.50 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.3	190.44 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.4
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Change from Baseline at Day 42	0.943 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 17.2	1.001 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 15.1	0.940 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 14.2
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Baseline for Day 56 Analysis	192.25 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.5	182.39 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.5	190.33 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 21.0
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Change from Baseline at Day 56	0.963 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 17.2	1.033 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 16.1	1.002 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 15.2
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Change from Baseline at Day 7	0.876 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 38.8	0.854 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 25.8	1.020 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 28.6
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Change from Baseline at Day 14	0.864 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 36.2	0.881 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 28.1	1.013 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 35.9
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Baseline for Day 84 Analysis	163.71 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 48.6	201.96 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 49.5	184.99 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 59.7
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Baseline for Day 7 Analysis	184.85 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 23.0	183.30 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.1	188.97 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.0
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Change from Baseline at Day 7	0.957 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 14.5	1.001 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 9.0	1.002 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 10.2
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Change from Baseline at Day 14	0.963 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 17.0	1.037 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 11.8	1.000 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 10.4
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Change from Baseline at Day 28	0.952 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 15.2	1.025 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 14.6	1.007 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 12.2
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Baseline for Day 42 Analysis	206.50 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 18.3	182.59 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.3	191.65 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 21.1
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Baseline for Day 84 Analysis	188.88 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.0	181.63 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.4	187.20 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 23.6
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Change from Baseline at Day 84	0.958 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 17.9	1.037 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 18.9	1.006 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 13.5
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Baseline for Day 112 (EOS) Analysis	187.34 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.8	181.47 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 22.0	187.13 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 23.1
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) Chol: Change from Baseline at Day 112 (EOS)	0.989 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 13.6	1.039 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 16.8	1.009 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 13.2
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Baseline for Day 7 Analysis	185.66 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 55.0	198.88 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 47.8	175.18 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 58.7
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Baseline for Day 14 Analysis	178.22 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 50.5	198.88 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 47.8	175.18 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 58.7
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Baseline for Day 28 Analysis	166.54 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 45.0	201.00 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 47.7	177.66 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 60.6
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Change from Baseline at Day 28	0.968 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 36.4	0.937 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 37.0	0.971 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 33.7
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Baseline for Day 42 Analysis	181.97 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 44.6	203.65 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 47.4	174.48 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 64.4
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Change from Baseline at Day 42	0.868 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 34.5	0.872 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 36.1	0.920 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 35.2
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Baseline for Day 56 Analysis	167.66 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 47.5	202.64 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 48.8	174.78 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 60.6
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Change from Baseline at Day 56	0.932 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 34.2	0.948 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 38.9	0.965 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 28.1
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Change from Baseline at Day 84	0.863 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 43.8	0.956 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 45.8	0.947 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 33.3
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Baseline for Day 112 (EOS) Analysis	172.80 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 46.1	203.55 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 49.2	179.36 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 62.5
Change From Baseline in Fasting Lipid Profile: Cholesterol (Chol) and Triglycerides (TG) TG: Change from Baseline at Day 112 (EOS)	0.931 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 38.5	1.003 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 39.9	1.039 milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 39.0

Measure	LMB763 100 mg n=37 Participants LMB763 100 mg capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	LMB763 50 mg n=44 Participants LMB763 50 mg (2 x 25 mg) capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).	Pooled Placebo n=40 Participants LMB763 100 mg or 50 mg matching placebo capsules, orally, once daily for 12 weeks (84 days) under fasted conditions (no food or drink for at least 6 hours).
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Change from Baseline at Day 7	0.874 millimole per liter (mmol/L) Geometric Coefficient of Variation 15.0	0.969 millimole per liter (mmol/L) Geometric Coefficient of Variation 10.0	1.017 millimole per liter (mmol/L) Geometric Coefficient of Variation 12.7
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Baseline for Day 56 Analysis	1.148 millimole per liter (mmol/L) Geometric Coefficient of Variation 25.5	1.008 millimole per liter (mmol/L) Geometric Coefficient of Variation 25.9	1.226 millimole per liter (mmol/L) Geometric Coefficient of Variation 29.1
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Baseline for Day 7 Analysis	2.647 millimole per liter (mmol/L) Geometric Coefficient of Variation 39.0	2.591 millimole per liter (mmol/L) Geometric Coefficient of Variation 40.6	2.628 millimole per liter (mmol/L) Geometric Coefficient of Variation 34.2
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Baseline for Day 112 (EOS) Analysis	2.695 millimole per liter (mmol/L) Geometric Coefficient of Variation 31.6	2.418 millimole per liter (mmol/L) Geometric Coefficient of Variation 40.0	2.482 millimole per liter (mmol/L) Geometric Coefficient of Variation 36.2
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Change from Baseline at Day 112 (EOS)	1.010 millimole per liter (mmol/L) Geometric Coefficient of Variation 18.7	1.035 millimole per liter (mmol/L) Geometric Coefficient of Variation 34.1	1.026 millimole per liter (mmol/L) Geometric Coefficient of Variation 19.9
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Baseline for Day 56 Analysis	2.841 millimole per liter (mmol/L) Geometric Coefficient of Variation 32.0	2.527 millimole per liter (mmol/L) Geometric Coefficient of Variation 42.0	2.621 millimole per liter (mmol/L) Geometric Coefficient of Variation 36.0
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Baseline for Day 7 Analysis	1.059 millimole per liter (mmol/L) Geometric Coefficient of Variation 30.0	1.014 millimole per liter (mmol/L) Geometric Coefficient of Variation 25.4	1.206 millimole per liter (mmol/L) Geometric Coefficient of Variation 28.2
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Baseline for Day 14 Analysis	1.093 millimole per liter (mmol/L) Geometric Coefficient of Variation 24.8	1.014 millimole per liter (mmol/L) Geometric Coefficient of Variation 25.4	1.206 millimole per liter (mmol/L) Geometric Coefficient of Variation 28.2
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Change from Baseline at Day 14	0.876 millimole per liter (mmol/L) Geometric Coefficient of Variation 19.1	0.982 millimole per liter (mmol/L) Geometric Coefficient of Variation 13.4	0.979 millimole per liter (mmol/L) Geometric Coefficient of Variation 10.0
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Baseline for Day 28 Analysis	1.143 millimole per liter (mmol/L) Geometric Coefficient of Variation 23.8	1.014 millimole per liter (mmol/L) Geometric Coefficient of Variation 25.7	1.221 millimole per liter (mmol/L) Geometric Coefficient of Variation 28.9
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Change from Baseline at Day 28	0.862 millimole per liter (mmol/L) Geometric Coefficient of Variation 14.1	0.952 millimole per liter (mmol/L) Geometric Coefficient of Variation 15.1	1.009 millimole per liter (mmol/L) Geometric Coefficient of Variation 14.7
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Baseline for Day 42 Analysis	1.172 millimole per liter (mmol/L) Geometric Coefficient of Variation 26.9	1.007 millimole per liter (mmol/L) Geometric Coefficient of Variation 25.7	1.212 millimole per liter (mmol/L) Geometric Coefficient of Variation 30.6
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Change from Baseline at Day 42	0.888 millimole per liter (mmol/L) Geometric Coefficient of Variation 19.4	0.941 millimole per liter (mmol/L) Geometric Coefficient of Variation 15.5	1.005 millimole per liter (mmol/L) Geometric Coefficient of Variation 12.2
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Change from Baseline at Day 56	0.875 millimole per liter (mmol/L) Geometric Coefficient of Variation 17.0	0.956 millimole per liter (mmol/L) Geometric Coefficient of Variation 15.1	1.022 millimole per liter (mmol/L) Geometric Coefficient of Variation 13.9
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Baseline for Day 84 Analysis	1.158 millimole per liter (mmol/L) Geometric Coefficient of Variation 24.9	1.016 millimole per liter (mmol/L) Geometric Coefficient of Variation 26.6	1.219 millimole per liter (mmol/L) Geometric Coefficient of Variation 29.7
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Change from Baseline at Day 84	0.891 millimole per liter (mmol/L) Geometric Coefficient of Variation 16.1	0.920 millimole per liter (mmol/L) Geometric Coefficient of Variation 19.9	1.031 millimole per liter (mmol/L) Geometric Coefficient of Variation 12.5
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Baseline for Day 112 (EOS) Analysis	1.115 millimole per liter (mmol/L) Geometric Coefficient of Variation 22.1	1.013 millimole per liter (mmol/L) Geometric Coefficient of Variation 26.1	1.218 millimole per liter (mmol/L) Geometric Coefficient of Variation 29.6
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol HDL: Change from Baseline at Day 112 (EOS)	1.004 millimole per liter (mmol/L) Geometric Coefficient of Variation 14.5	1.037 millimole per liter (mmol/L) Geometric Coefficient of Variation 17.2	1.007 millimole per liter (mmol/L) Geometric Coefficient of Variation 11.5
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Change from Baseline at Day 7	1.009 millimole per liter (mmol/L) Geometric Coefficient of Variation 18.7	1.076 millimole per liter (mmol/L) Geometric Coefficient of Variation 20.2	0.977 millimole per liter (mmol/L) Geometric Coefficient of Variation 17.1
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Baseline for Day 14 Analysis	2.664 millimole per liter (mmol/L) Geometric Coefficient of Variation 39.8	2.591 millimole per liter (mmol/L) Geometric Coefficient of Variation 40.6	2.666 millimole per liter (mmol/L) Geometric Coefficient of Variation 34.3
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Change from Baseline at Day 14	1.021 millimole per liter (mmol/L) Geometric Coefficient of Variation 23.6	1.125 millimole per liter (mmol/L) Geometric Coefficient of Variation 19.7	0.998 millimole per liter (mmol/L) Geometric Coefficient of Variation 14.3
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Baseline for Day 28 Analysis	2.612 millimole per liter (mmol/L) Geometric Coefficient of Variation 39.4	2.553 millimole per liter (mmol/L) Geometric Coefficient of Variation 40.7	2.614 millimole per liter (mmol/L) Geometric Coefficient of Variation 36.3
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Change from Baseline at Day 28	0.996 millimole per liter (mmol/L) Geometric Coefficient of Variation 27.5	1.092 millimole per liter (mmol/L) Geometric Coefficient of Variation 23.0	1.017 millimole per liter (mmol/L) Geometric Coefficient of Variation 15.7
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Baseline for Day 42 Analysis	3.070 millimole per liter (mmol/L) Geometric Coefficient of Variation 28.7	2.559 millimole per liter (mmol/L) Geometric Coefficient of Variation 41.0	2.679 millimole per liter (mmol/L) Geometric Coefficient of Variation 35.1
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Change from Baseline at Day 42	0.989 millimole per liter (mmol/L) Geometric Coefficient of Variation 29.9	1.079 millimole per liter (mmol/L) Geometric Coefficient of Variation 24.5	0.914 millimole per liter (mmol/L) Geometric Coefficient of Variation 21.1
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Change from Baseline at Day 56	1.011 millimole per liter (mmol/L) Geometric Coefficient of Variation 27.9	1.091 millimole per liter (mmol/L) Geometric Coefficient of Variation 24.8	0.991 millimole per liter (mmol/L) Geometric Coefficient of Variation 24.7
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Baseline for Day 84 Analysis	2.725 millimole per liter (mmol/L) Geometric Coefficient of Variation 30.8	2.528 millimole per liter (mmol/L) Geometric Coefficient of Variation 41.8	2.498 millimole per liter (mmol/L) Geometric Coefficient of Variation 36.8
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) and Low-density Lipoprotein (LDL) Cholesterol LDL: Change from Baseline at Day 84	1.029 millimole per liter (mmol/L) Geometric Coefficient of Variation 22.5	1.107 millimole per liter (mmol/L) Geometric Coefficient of Variation 31.7	1.025 millimole per liter (mmol/L) Geometric Coefficient of Variation 22.2