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Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in NAFLD Patients

Primary Purpose

Non-alcoholic Fatty Liver Disease (NAFLD)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LCQ908
placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Fatty Liver Disease (NAFLD) focused on measuring Multi-center,, randomized,, double-blind,, NAFLD,, elevated triglycerides

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • History of liver steatosis during the preceding 24 months
  • History of fasting TGs > 200 mg/dL (confirmed at screening).
  • Liver fat ≥ 10% as determined by the central MRI laboratory.

  • Subjects on the following medications can be included if these medications are medically necessary, cannot be stopped and the investigator feels their dose will remain stable for the duration of the double-blind treatment period:

    1. Stable dose of anti-diabetic medications (metformin and/or sulfonylureas) for at least 8 weeks prior to screening.
    2. Stable doses of beta-blockers and thiazide diuretics for at least 8 weeks prior to screening.
    3. Stable doses of fibrates, statins, niacin, ezetimibe for at least 8 weeks prior to screening.
    4. Stable dose of vitamin E in patients taking >200 IU/day for at least 6 months prior to screening.

Exclusion Criteria:

  • Treatment with omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements > 200 mg per day within 8 weeks of screening.
  • Treatment with antiretrovirals, tamoxifen, methotrexate, cyclophosphamide, isotretinoin, bile acid binding resins or pharmacologic doses of oral glucocorticoids (≥10 mg of prednisone per day or equivalent) within 8 weeks of screening.
  • ALT or AST > 250 IU/L at the time of screening.
  • History/current evidence of heavy alcohol use or alcoholism (> 21 drinks per week in men and > 14 drinks per week in women) over a 2-year period prior to screening.
  • Presence of chronic liver disease, such as chronic hepatitis B and/or C, alcoholic liver disease, hemochromatosis, Wilson's disease, known cirrhosis.
  • Platelet count <150,000 at screening.
  • BMI >45 Kg/m2.

Other protocol defined inclusion/exclusion criteria may apply

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

pradigastat (LCQ908) 5mg/10mg

pradigastat (LCQ908) 10mg/20mg

Arm Description

Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.

Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.

Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.

Outcomes

Primary Outcome Measures

Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24
Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).

Secondary Outcome Measures

Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 12
Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).
Percentage of Responders at Week 12
The response criteria are defined as: a. A reduction of ≥ 30% from baseline in liver fat b. A reduction of ≥ 50% from baseline in liver fat c. Liver fat content < 10% d. Liver fat content < 5.6%. Percentage is calculated as (m/n)*100 where m: number of patients who are responders. n: number of patients with non-missing percent liver fat at that visit.
Percentage of Responders at Week 24
The response criteria are defined as: a. A reduction of ≥ 30% from baseline in liver fat b. A reduction of ≥ 50% from baseline in liver fat c. Liver fat content < 10% d. Liver fat content < 5.6%. Percentage is calculated as (m/n)*100 where m: number of patients who are responders. n: number of patients with non-missing percent liver fat at that visit.
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6
Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization). Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12
Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization). Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24
Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization). Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.
Percentage of Patients With Normalized Liver Enzymes
Normalized liver enzymes defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 40 U/L. Normal/High categories at baseline are defined by criteria of normal. Better is defined as high' at baseline and 'normal' post-dose; Same is defined as 'normal' at baseline and 'normal' post-dose or 'high' at baseline and 'high' post-dose; Worse is defined as 'normal' at baseline and 'high' post-dose.
Percent Change From Baseline in Fasting Triglycerides
Blood samples were collected for a fasting triglycerides (TG) after a 10-hour (overnight) fast. Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline. Baseline is defined as the value collected at Week 0 (randomization).
Post-prandial Peak Triglycerides Over 0 - 8 Hours
Post-prandial peak triglycerides is reported as maximum triglyceride value over 0-8 hours. Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model. Baseline is defined as the value collected at Week 0 (randomization).
Change From Baseline in Body Weight
Change From Baseline in Waist Circumference
Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability

Full Information

First Posted
March 12, 2013
Last Updated
January 5, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01811472
Brief Title
Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in NAFLD Patients
Official Title
A Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group, 24-week Pilot Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in Patients With Non-alcoholic Fatty Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study was to determine whether LCQ908 effectively lowers liver fat, as assessed by MRI and to assess its safety and tolerability profile in subjects with non-alcoholic fatty liver disease (NAFLD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease (NAFLD)
Keywords
Multi-center,, randomized,, double-blind,, NAFLD,, elevated triglycerides

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Arm Title
pradigastat (LCQ908) 5mg/10mg
Arm Type
Experimental
Arm Description
Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Arm Title
pradigastat (LCQ908) 10mg/20mg
Arm Type
Experimental
Arm Description
Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.
Intervention Type
Drug
Intervention Name(s)
LCQ908
Other Intervention Name(s)
pradigastat
Intervention Description
LCQ908 5 mg, 10 mg, 20 mg tablets
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Matching placebo of LCQ908 5 mg, 10 mg, 20 mg tablets.
Primary Outcome Measure Information:
Title
Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24
Description
Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).
Time Frame
From baseline to week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 12
Description
Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).
Time Frame
From baseline to week 12
Title
Percentage of Responders at Week 12
Description
The response criteria are defined as: a. A reduction of ≥ 30% from baseline in liver fat b. A reduction of ≥ 50% from baseline in liver fat c. Liver fat content < 10% d. Liver fat content < 5.6%. Percentage is calculated as (m/n)*100 where m: number of patients who are responders. n: number of patients with non-missing percent liver fat at that visit.
Time Frame
At week 12
Title
Percentage of Responders at Week 24
Description
The response criteria are defined as: a. A reduction of ≥ 30% from baseline in liver fat b. A reduction of ≥ 50% from baseline in liver fat c. Liver fat content < 10% d. Liver fat content < 5.6%. Percentage is calculated as (m/n)*100 where m: number of patients who are responders. n: number of patients with non-missing percent liver fat at that visit.
Time Frame
From baseline to week 24
Title
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6
Description
Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization). Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.
Time Frame
From Baseline to week 6
Title
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12
Description
Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization). Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.
Time Frame
From Baseline to week 12
Title
Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24
Description
Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization). Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.
Time Frame
From Baseline to week 24
Title
Percentage of Patients With Normalized Liver Enzymes
Description
Normalized liver enzymes defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 40 U/L. Normal/High categories at baseline are defined by criteria of normal. Better is defined as high' at baseline and 'normal' post-dose; Same is defined as 'normal' at baseline and 'normal' post-dose or 'high' at baseline and 'high' post-dose; Worse is defined as 'normal' at baseline and 'high' post-dose.
Time Frame
Baseline, week 6, week 12 and week 24
Title
Percent Change From Baseline in Fasting Triglycerides
Description
Blood samples were collected for a fasting triglycerides (TG) after a 10-hour (overnight) fast. Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline. Baseline is defined as the value collected at Week 0 (randomization).
Time Frame
Baseline, 6, 12 and 24 weeks
Title
Post-prandial Peak Triglycerides Over 0 - 8 Hours
Description
Post-prandial peak triglycerides is reported as maximum triglyceride value over 0-8 hours. Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model. Baseline is defined as the value collected at Week 0 (randomization).
Time Frame
Baseline, 6 and 24 weeks
Title
Change From Baseline in Body Weight
Time Frame
Baseline, 12 and 24 weeks
Title
Change From Baseline in Waist Circumference
Time Frame
Baseline, 12 and 24 weeks
Title
Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: History of liver steatosis during the preceding 24 months History of fasting TGs > 200 mg/dL (confirmed at screening). Liver fat ≥ 10% as determined by the central MRI laboratory. Subjects on the following medications can be included if these medications are medically necessary, cannot be stopped and the investigator feels their dose will remain stable for the duration of the double-blind treatment period: Stable dose of anti-diabetic medications (metformin and/or sulfonylureas) for at least 8 weeks prior to screening. Stable doses of beta-blockers and thiazide diuretics for at least 8 weeks prior to screening. Stable doses of fibrates, statins, niacin, ezetimibe for at least 8 weeks prior to screening. Stable dose of vitamin E in patients taking >200 IU/day for at least 6 months prior to screening. Exclusion Criteria: Treatment with omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements > 200 mg per day within 8 weeks of screening. Treatment with antiretrovirals, tamoxifen, methotrexate, cyclophosphamide, isotretinoin, bile acid binding resins or pharmacologic doses of oral glucocorticoids (≥10 mg of prednisone per day or equivalent) within 8 weeks of screening. ALT or AST > 250 IU/L at the time of screening. History/current evidence of heavy alcohol use or alcoholism (> 21 drinks per week in men and > 14 drinks per week in women) over a 2-year period prior to screening. Presence of chronic liver disease, such as chronic hepatitis B and/or C, alcoholic liver disease, hemochromatosis, Wilson's disease, known cirrhosis. Platelet count <150,000 at screening. BMI >45 Kg/m2. Other protocol defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Novartis Investigative Site
City
San Diego
State/Province
California
ZIP/Postal Code
92114
Country
United States
Facility Name
Novartis Investigative Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0277
Country
United States
Facility Name
Novartis Investigative Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
Novartis Investigative Site
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33319
Country
United States
Facility Name
Novartis Investigative Site
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96814
Country
United States
Facility Name
Novartis Investigative Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40213
Country
United States
Facility Name
Novartis Investigative Site
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
Novartis Investigative Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in NAFLD Patients

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