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

NCT01811472 | Completed Phase 2 Results

• 2 other identifiers: CLCQ908A22162013-000049-38
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 11

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).

Conditions

Non-alcoholic Fatty Liver Disease (NAFLD)

Keywords

Multi-center,; randomized,; double-blind,; NAFLD,; elevated triglycerides

Outcome Measures

Primary Outcomes (1)

• 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).

  From baseline to week 24

Secondary Outcomes (12)

• Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 12

  From baseline to week 12

• Percentage of Responders at Week 12

  At week 12

• Percentage of Responders at Week 24

  From baseline to week 24

• Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6

  From Baseline to week 6

• Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12

  From Baseline to week 12

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

pradigastat (LCQ908) 5mg/10mg

EXPERIMENTAL

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

pradigastat (LCQ908) 10mg/20mg

EXPERIMENTAL

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

Interventions

LCQ908 DRUG

LCQ908 5 mg, 10 mg, 20 mg tablets

Also known as: pradigastat

pradigastat (LCQ908) 10mg/20mg; pradigastat (LCQ908) 5mg/10mg

placebo DRUG

Matching placebo of LCQ908 5 mg, 10 mg, 20 mg tablets.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Mobile, Alabama, 36608, United States

Location

Novartis Investigative Site

San Diego, California, 92114, United States

Location

Novartis Investigative Site

Gainesville, Florida, 32610-0277, United States

Location

Novartis Investigative Site

Miami, Florida, 33126, United States

Location

Novartis Investigative Site

Tamarac, Florida, 33319, United States

Location

Novartis Investigative Site

Honolulu, Hawaii, 96814, United States

Location

Novartis Investigative Site

Louisville, Kentucky, 40213, United States

Location

Novartis Investigative Site

Tupelo, Mississippi, 38801, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Plano, Texas, 75093, United States

Location

Novartis Investigative Site

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Hypertriglyceridemia

Interventions

pradigastat

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2013
• First Posted: March 14, 2013
• Study Start: June 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: February 4, 2016
• Results First Posted: February 4, 2016

Record last verified: 2016-01

Locations

US (11)