search
Back to results

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

Primary Purpose

Obese Patients With Non-alcoholic Steatohepatitis (NASH)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LIK066
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obese Patients With Non-alcoholic Steatohepatitis (NASH) focused on measuring non-alcoholic steatohepatitis, NASH, Obese, Type 2 diabetes mellitus, non-alcoholic fatty liver disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

EITHER

-Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3 in the absence of a histological diagnosis of alternative chronic liver disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening.

OR

Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening:

  • ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND
  • BMI greater than or equal to 27 kg/m^2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m^2 (in patients with a self identified Asian race) AND
  • Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10%
  • Patients must weigh no more than 150 kg (330 lbs) to participate in the study.
  • Male and female patients 18 years or older at the time of screening visit.

Exclusion Criteria:

  • History or presence of other concomitant liver diseases
  • History or current diagnosis of ECG abnormalities
  • Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study
  • Patients with contraindications to MRI imaging
  • Current or history of significant alcohol consumption
  • Clinical evidence of hepatic decompensation or severe liver impairment
  • Women of child bearing potential (unless on basic contraception methods)
  • Presence of liver cirrhosis

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

LIK066 30 mg

LIK066 150 mg

Placebo

Arm Description

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.

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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).
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).
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).
Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration
Cmax is the observed maximum plasma concentration following drug administration (ng/mL)
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 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)
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.

Full Information

First Posted
June 28, 2017
Last Updated
October 7, 2021
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT03205150
Brief Title
Effect of LIK066 on Reduction of Fatty Content in Livers of Obese Patients
Official Title
A 12-week Randomized, Patient and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate the Efficacy of LIK066 in Obese Patients With Non-alcoholic Steatohepatitis (NASH)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
October 4, 2017 (Actual)
Primary Completion Date
November 11, 2019 (Actual)
Study Completion Date
November 14, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study was to assess the effects of LIK066 on a variety of metabolic and inflammation biomarkers in patients with non-alcoholic steatohepatitis (NASH)
Detailed Description
This was a a non-confirmatory, multicenter, patient and investigator blinded, randomized, placebo-controlled, parallel group study in patients with non-alcoholic steatohepatitis (NASH). The study consisted of a 28 day screening period (Day -44 to Day -16), a baseline period of 14 days (Day -15 to Day -1), a treatment period of 12 weeks (Day 1 to Day 84), and a study completion evaluation approximately 28 days after the last drug administration. The patients were advised to maintain their recommended diet during the study. Patients who met the inclusion/exclusion criteria at screening went to the study site for baseline assessments. All baseline safety evaluation results were available prior to the first dosing. The study started by enrolling patients into the 150 mg and placebo arms with a randomization ratio of 2:1. After the enrollment of the first 33 patients, the 30 mg arm was added to the study and the randomization ratio changed to a 2:4:1 ratio (150 mg: 30 mg: placebo) to maintain the 2:2:1 ratio across the three groups (150 mg: 30 mg: placebo) at study completion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obese Patients With Non-alcoholic Steatohepatitis (NASH)
Keywords
non-alcoholic steatohepatitis, NASH, Obese, Type 2 diabetes mellitus, non-alcoholic fatty liver disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
107 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LIK066 30 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
LIK066 150 mg
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LIK066
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Alanine Aminotransferase (ALT) at Week 12
Description
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.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Percent Liver Fat at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Percent Change From Baseline in Total Body Weight at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Change From Baseline in the Concentration of Hyaluronic Acid at Week 12.
Description
Hyaluronic Acid is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).
Time Frame
Baseline, Week 12
Title
Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12.
Description
PIIINP is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).
Time Frame
Baseline, Week 12
Title
Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12.
Description
TIMP-1 is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF).
Time Frame
Baseline, Week 12
Title
Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration
Description
Cmax is the observed maximum plasma concentration following drug administration (ng/mL)
Time Frame
Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)
Title
Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration
Description
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.
Time Frame
Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)
Title
Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration
Description
AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (hour*ng/mL)
Time Frame
Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)
Title
Change From Baseline in Aspartate Aminotransferase (AST) at Week 12
Description
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.
Time Frame
Baseline, Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: EITHER -Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3 in the absence of a histological diagnosis of alternative chronic liver disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening. OR Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening: ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND BMI greater than or equal to 27 kg/m^2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m^2 (in patients with a self identified Asian race) AND Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10% Patients must weigh no more than 150 kg (330 lbs) to participate in the study. Male and female patients 18 years or older at the time of screening visit. Exclusion Criteria: History or presence of other concomitant liver diseases History or current diagnosis of ECG abnormalities Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study Patients with contraindications to MRI imaging Current or history of significant alcohol consumption Clinical evidence of hepatic decompensation or severe liver impairment Women of child bearing potential (unless on basic contraception methods) Presence of liver cirrhosis
Facility Information:
Facility Name
Novartis Investigative Site
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Novartis Investigative Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Novartis Investigative Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Novartis Investigative Site
City
Live Oak
State/Province
Texas
ZIP/Postal Code
78233
Country
United States
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1056ABJ
Country
Argentina
Facility Name
Novartis Investigative Site
City
Buenos Aires
ZIP/Postal Code
C1120AAC
Country
Argentina
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3P 3P1
Country
Canada
Facility Name
Novartis Investigative Site
City
Haifa
ZIP/Postal Code
343621
Country
Israel
Facility Name
Novartis Investigative Site
City
Ramat Gan
Country
Israel
Facility Name
Novartis Investigative Site
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Novartis Investigative Site
City
Leiden
ZIP/Postal Code
2333 CL
Country
Netherlands
Facility Name
Novartis Investigative Site
City
St-Petersburg
ZIP/Postal Code
194358
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Chia-Yi
ZIP/Postal Code
60002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Tainan
ZIP/Postal Code
70403
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
35725922
Citation
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.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=700
Description
A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

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

We'll reach out to this number within 24 hrs