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

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ClinicalTrials.gov Identifier: NCT01811472
Recruitment Status : Completed
First Posted : March 14, 2013
Results First Posted : February 4, 2016
Last Update Posted : February 4, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease Intervention/treatment Phase
Non-alcoholic Fatty Liver Disease (NAFLD) Drug: LCQ908 Drug: placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : June 2013
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014


Arm Intervention/treatment
Placebo Comparator: Placebo
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.
Drug: placebo
Matching placebo of LCQ908 5 mg, 10 mg, 20 mg tablets.

Experimental: pradigastat (LCQ908) 5mg/10mg
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.
Drug: LCQ908
LCQ908 5 mg, 10 mg, 20 mg tablets
Other Name: pradigastat

Experimental: pradigastat (LCQ908) 10mg/20mg
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.
Drug: LCQ908
LCQ908 5 mg, 10 mg, 20 mg tablets
Other Name: pradigastat




Primary Outcome Measures :
  1. Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24 [ Time Frame: From baseline to 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 :
  1. Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 12 [ Time Frame: From baseline to 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).

  2. Percentage of Responders at Week 12 [ Time Frame: 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.


  3. Percentage of Responders at Week 24 [ Time Frame: From baseline to 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.


  4. Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6 [ Time Frame: From Baseline 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.


  5. Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12 [ Time Frame: From Baseline 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.


  6. Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24 [ Time Frame: From Baseline 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.


  7. Percentage of Patients With Normalized Liver Enzymes [ Time Frame: Baseline, week 6, week 12 and week 24 ]
    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.

  8. Percent Change From Baseline in Fasting Triglycerides [ Time Frame: Baseline, 6, 12 and 24 weeks ]

    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).


  9. Post-prandial Peak Triglycerides Over 0 - 8 Hours [ Time Frame: Baseline, 6 and 24 weeks ]

    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).


  10. Change From Baseline in Body Weight [ Time Frame: Baseline, 12 and 24 weeks ]
  11. Change From Baseline in Waist Circumference [ Time Frame: Baseline, 12 and 24 weeks ]
  12. Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability [ Time Frame: 24 weeks ]


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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01811472


Locations
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United States, Alabama
Novartis Investigative Site
Mobile, Alabama, United States, 36608
United States, California
Novartis Investigative Site
San Diego, California, United States, 92114
United States, Florida
Novartis Investigative Site
Gainesville, Florida, United States, 32610-0277
Novartis Investigative Site
Miami, Florida, United States, 33126
Novartis Investigative Site
Tamarac, Florida, United States, 33319
United States, Hawaii
Novartis Investigative Site
Honolulu, Hawaii, United States, 96814
United States, Kentucky
Novartis Investigative Site
Louisville, Kentucky, United States, 40213
United States, Mississippi
Novartis Investigative Site
Tupelo, Mississippi, United States, 38801
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
Novartis Investigative Site
Plano, Texas, United States, 75093
United States, Virginia
Novartis Investigative Site
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01811472     History of Changes
Other Study ID Numbers: CLCQ908A2216
2013-000049-38 ( EudraCT Number )
First Posted: March 14, 2013    Key Record Dates
Results First Posted: February 4, 2016
Last Update Posted: February 4, 2016
Last Verified: January 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Multi-center,
randomized,
double-blind,
NAFLD,
elevated triglycerides

Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases