Trial Outcomes & Findings for Effect of LIK066 on Reduction of Fatty Content in Livers of Obese Patients (NCT NCT03205150)

NCT ID: NCT03205150

Last Updated: 2021-10-08

Results Overview

Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

107 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2021-10-08

Participant Flow

A total of 107 participants were enrolled in 15 centers across 8 countries: Argentina (2), Canada (1), Israel (3), Netherlands (1), Russia federation (1), Taiwan (2), Thailand (1), United States (4).

Participants were randomized in 2:2:1 ratio to the 3 groups: LIK066 150 mg, LIK066 30 mg and placebo.

Participant milestones

Participant milestones
Measure	LIK066 30 mg Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Overall Study STARTED	43	43	21
Overall Study Safety Analysis Set	43	43	21
Overall Study Pharmacokinetics (PK) Analysis Set	42	36	0
Overall Study Pharmacodynamics (PD) Analysis Set	43	41	21
Overall Study COMPLETED	41	36	19
Overall Study NOT COMPLETED	2	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	LIK066 30 mg Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Overall Study Protocol deviation	1	3	0
Overall Study Patient/guardian decision	0	3	0
Overall Study Adverse Event	1	1	1
Overall Study Lost to Follow-up	0	0	1

Baseline Characteristics

Effect of LIK066 on Reduction of Fatty Content in Livers of Obese Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 30 mg n=43 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=43 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Total n=107 Participants Total of all reporting groups
Age, Continuous	48.0 years STANDARD_DEVIATION 11.16 • n=99 Participants	53.1 years STANDARD_DEVIATION 12.57 • n=107 Participants	49.5 years STANDARD_DEVIATION 11.10 • n=206 Participants	50.7 years STANDARD_DEVIATION 11.80 • n=7 Participants
Sex: Female, Male Female	12 Participants n=99 Participants	25 Participants n=107 Participants	22 Participants n=206 Participants	59 Participants n=7 Participants
Sex: Female, Male Male	9 Participants n=99 Participants	18 Participants n=107 Participants	21 Participants n=206 Participants	48 Participants n=7 Participants
Race/Ethnicity, Customized White	17 Participants n=99 Participants	34 Participants n=107 Participants	35 Participants n=206 Participants	86 Participants n=7 Participants
Race/Ethnicity, Customized Asian	3 Participants n=99 Participants	8 Participants n=107 Participants	4 Participants n=206 Participants	15 Participants n=7 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants	5 Participants n=7 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=40 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=34 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=20 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Change From Baseline in Alanine Aminotransferase (ALT) at Week 12	-22.06 Units per Liter (U/L) Standard Error 4.16	-30.41 Units per Liter (U/L) Standard Error 4.52	-8.77 Units per Liter (U/L) Standard Error 5.99

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

Percent (%) Liver fat was measured by Magnetic Resonance Imaging Proton Density Liver Fat Fraction(MRIPDFF). Patients underwent magnetic resonance imaging twice during the course of the study ( baseline and end of treatment) to quantitate liver fat.

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=39 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=33 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=19 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Change From Baseline in Percent Liver Fat at Week 12	-4.40 Percentage of Liver Fat Standard Error 0.81	-6.92 Percentage of Liver Fat Standard Error 0.87	-2.67 Percentage of Liver Fat Standard Error 1.17

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

Body weight (to the nearest 0.1 kilogram \[kg\] was measured on a calibrated scale. The measurement was performed with the study subject in underwear and without shoes; or while wearing minimal indoor clothing.

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=40 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=34 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=19 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Percent Change From Baseline in Total Body Weight at Week 12	-3.48 percentage change Standard Error 0.47	-4.51 percentage change Standard Error 0.52	-0.33 percentage change Standard Error 0.68

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

The markers of fibrosis assessed in this test comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during fibrogenesis as a result of activation of the hepatic stellate cell. The ELF test is a composite score: \< 7.7: no to mild fibrosis; ≥ 7.7 - \< 9.8: Moderate fibrosis; ≥ 9.8 - \< 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis.

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=40 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=34 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=21 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12	-0.2 scores on a scale Standard Deviation 0.65	-0.1 scores on a scale Standard Deviation 0.61	0.1 scores on a scale Standard Deviation 0.37

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

Hyaluronic Acid is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=40 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=34 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=21 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Change From Baseline in the Concentration of Hyaluronic Acid at Week 12.	-3.4 ug/L Standard Deviation 75.38	0.4 ug/L Standard Deviation 30.56	4.7 ug/L Standard Deviation 21.73

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

PIIINP is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=40 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=34 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=20 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12.	-1.7 ug/L Standard Deviation 2.73	-1.2 ug/L Standard Deviation 3.66	0.3 ug/L Standard Deviation 1.88

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

TIMP-1 is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=40 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=34 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=20 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12.	-3.0 ug/L Standard Deviation 38.98	-10.9 ug/L Standard Deviation 38.21	10.3 ug/L Standard Deviation 25.73

SECONDARY outcome

Timeframe: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)

Population: Pharmacokinetics (PK) analysis set consisted of LIK066 treated patients. Placebo patients were excluded from the PK analysis

Cmax is the observed maximum plasma concentration following drug administration (ng/mL)

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=38 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=32 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration	405 ng/mL Standard Deviation 109	1810 ng/mL Standard Deviation 729	—

SECONDARY outcome

Timeframe: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)

Population: Pharmacokinetics (PK) analysis set consisted of LIK066 treated patients. Placebo patients were excluded from the PK analysis

Tmax is the time to reach the maximum concentration after drug administration (hour). The time points presented are the actual and not the planned time points.

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=38 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=32 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration	1.00 hours Interval 0.5 to 6.0	1.51 hours Interval 0.567 to 6.0	—

SECONDARY outcome

Timeframe: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)

Population: Pharmacokinetics (PK) analysis set consisted of LIK066 treated patients. Placebo patients were excluded from the PK analysis

AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (hour\*ng/mL)

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=38 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=32 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration	1280 hour*ng/mL Standard Deviation 413	5770 hour*ng/mL Standard Deviation 1680	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Pharmacodynamics (PD) analysis set: included all participants with available PD data, who received any study drug and had valid measurements for the outcome measure

Aspartate aminotransferase (AST) is an enzyme found in many cells of the body specifically those of the liver, heart and skeletal muscle. In healthy individuals, levels of AST in the blood are low. When liver or muscle cells are injured, they release AST into the blood. In this study, the blood levels of AST was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits.

Outcome measures

Outcome measures
Measure	LIK066 30 mg n=40 Participants Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=34 Participants Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=20 Participants LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.
Change From Baseline in Aspartate Aminotransferase (AST) at Week 12	-13.45 Units per liter (U/L) Standard Error 2.46	-17.01 Units per liter (U/L) Standard Error 2.68	-2.30 Units per liter (U/L) Standard Error 3.54

Adverse Events

LIK066 30 mg

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

LIK066 150 mg

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

All Patients

Serious events: 1 serious events

Other events: 85 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LIK066 30 mg n=43 participants at risk Film coated tablet of LIK066 30 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	LIK066 150 mg n=43 participants at risk Film coated tablet of LIK066 150 mg was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	Placebo n=21 participants at risk LIK066 0 mg film-coated tablet(Placebo matching tablets) was mostly administered once daily before lunch, except on Day 56 when it was administered before breakfast and in fasted state on Day 84.	All Patients n=107 participants at risk All Patients
Infections and infestations Gastroenteritis viral	0.00% 0/43 • Adverse events were collected from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period. Any signs or symptoms that occured from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period.	0.00% 0/43 • Adverse events were collected from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period. Any signs or symptoms that occured from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period.	4.8% 1/21 • Adverse events were collected from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period. Any signs or symptoms that occured from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period.	0.93% 1/107 • Adverse events were collected from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period. Any signs or symptoms that occured from the first dose of study treatment until the end of study treatment i.e. Day 84 plus 28 days recovery and follow-up period.

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