Effect of LIK066 on Reduction of Fatty Content in Livers... | NCT03205150

ID	Type	Description	Link
2017-002046-71	EudraCT Number

Label	Type	Description	Intervention Names
LIK066 30 mg	Experimental	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.	Drug: LIK066
LIK066 150 mg	Experimental	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	Drug: LIK066
Placebo	Experimental	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.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
LIK066	Drug	Film coated tablet of LIK066 either 30mg or 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

Measure	Description	Time Frame
Change From Baseline in Alanine Aminotransferase (ALT) at Week 12	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.	Baseline, Week 12

Measure	Description	Time Frame
Change From Baseline in Percent Liver Fat at Week 12	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.	Baseline, Week 12

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Baton Rouge	Louisiana	70808	United States
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
35725922	Derived	Harrison SA, Manghi FP, Smith WB, Alpenidze D, Aizenberg D, Klarenbeek N, Chen CY, Zuckerman E, Ravussin E, Charatcharoenwitthaya P, Cheng PN, Katchman H, Klein S, Ben-Ari Z, Mendonza AE, Zhang Y, Martic M, Ma S, Kao S, Tanner S, Pachori A, Badman MK, He Y, Ukomadu C, Sicard E. Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study. Nat Med. 2022 Jul;28(7):1432-1438. doi: 10.1038/s41591-022-01861-9. Epub 2022 Jun 20.

Label	URL
A Plain Language Trial Summary is available on novartisclinicaltrials.com	View source

ID	Title	Description
FG000	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.
FG001	LIK066 150 mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 29, 2019	Nov 11, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Alanine Aminotransferase (ALT) at Week 12

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.

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

Posted

Mean

Standard Error

Units per Liter (U/L)

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts
Participants	OG00040 OG00134 OG00220

Title

Denominators

Categories

Title	Measurements
	OG000-22.06± 4.16 OG001-30.41± 4.52 OG002-8.77± 5.99

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		ANCOVA		0.075		Mean Difference (Net)	-13.29	Standard Error of the Mean	7.35	2-Sided	80	-22.80	-3.78					Superiority
OG001 OG002		ANCOVA		0.005

Secondary

Change From Baseline in Percent Liver Fat at Week 12

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.

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

Posted

Mean

Standard Error

Percentage of Liver Fat

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Percent Change From Baseline in Total Body Weight at Week 12

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.

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

Posted

Mean

Standard Error

percentage change

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12

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.

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

Posted

Mean

Standard Deviation

scores on a scale

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Change From Baseline in the Concentration of Hyaluronic Acid at Week 12.

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

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

Posted

Mean

Standard Deviation

ug/L

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12.

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

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

Posted

Mean

Standard Deviation

ug/L

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12.

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

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

Posted

Mean

Standard Deviation

ug/L

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration

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

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

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration

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.

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

Posted

Median

Full Range

hours

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration

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

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

Posted

Mean

Standard Deviation

hour*ng/mL

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Change From Baseline in Aspartate Aminotransferase (AST) at Week 12

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.

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

Posted

Mean

Standard Error

Units per liter (U/L)

Baseline, Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG0031 affected107 at risk
Palpitations	Cardiac disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0021 affected21 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Glaucoma	Eye disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0016 affected43 at risk EG0020 affected21 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0015 affected43 at risk EG0022 affected21 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0013 affected43 at risk EG0022 affected21 at risk EG003
Abdominal tenderness	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Anal pruritus	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0013 affected43 at risk EG0021 affected21 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG00021 affected43 at risk EG00133 affected43 at risk EG0029 affected21 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0011 affected43 at risk EG0021 affected21 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0018 affected43 at risk EG0022 affected21 at risk EG003
Gastric dilatation	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0004 affected43 at risk EG0013 affected43 at risk EG0023 affected21 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (22.1)	Systematic Assessment	EG0005 affected43 at risk EG0012 affected43 at risk EG0022 affected21 at risk EG003
Asthenia	General disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0011 affected43 at risk EG0021 affected21 at risk EG003
Chills	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Early satiety	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Fatigue	General disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0013 affected43 at risk EG0020 affected21 at risk EG003
Feeling hot	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Feeling jittery	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Hunger	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Pyrexia	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0021 affected21 at risk EG003
Thirst	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Vessel puncture site bruise	General disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Portal hypertension	Hepatobiliary disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Allergy to arthropod bite	Immune system disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Bronchitis	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Fungal infection	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Furuncle	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Gingival abscess	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Influenza	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0004 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0013 affected43 at risk EG0021 affected21 at risk EG003
Oral herpes	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Otitis externa	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Rhinitis	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Sinusitis	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0003 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Vaginal infection	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0012 affected43 at risk EG0020 affected21 at risk EG003
Viral infection	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Vulvovaginal mycotic infection	Infections and infestations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0012 affected43 at risk EG0020 affected21 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Blood cholesterol increased	Investigations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Blood triglycerides increased	Investigations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Heart rate irregular	Investigations	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Lymphocyte morphology abnormal	Investigations	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Food craving	Metabolism and nutrition disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Hypovitaminosis	Metabolism and nutrition disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Polydipsia	Metabolism and nutrition disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0021 affected21 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0022 affected21 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0022 affected21 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0012 affected43 at risk EG0021 affected21 at risk EG003
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Dizziness	Nervous system disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0014 affected43 at risk EG0023 affected21 at risk EG003
Head discomfort	Nervous system disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Headache	Nervous system disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0015 affected43 at risk EG0023 affected21 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Somnolence	Nervous system disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Tremor	Nervous system disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (22.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Depression	Psychiatric disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Mood swings	Psychiatric disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Nervousness	Psychiatric disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Ketonuria	Renal and urinary disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Microalbuminuria	Renal and urinary disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA (22.1)	Systematic Assessment	EG0004 affected43 at risk EG0011 affected43 at risk EG0021 affected21 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Nipple pain	Reproductive system and breast disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0020 affected21 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected43 at risk EG0021 affected21 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003
Papule	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Diastolic hypotension	Vascular disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Hypertension	Vascular disorders	MedDRA (22.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected43 at risk EG0020 affected21 at risk EG003
Peripheral coldness	Vascular disorders	MedDRA (22.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected43 at risk EG0021 affected21 at risk EG003

ID	Term
D065626	Non-alcoholic Fatty Liver Disease
D009765	Obesity
D003924	Diabetes Mellitus, Type 2

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D009750	Nutritional and Metabolic Diseases
D001835	Body Weight
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D004700	Endocrine System Diseases

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	43	0	43	31	43
EG001	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.	43	0	43	36	43
EG002	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.	21	1	21	18	21
EG003	All Patients	All Patients	107	1	107	85	107